Pathfinder - eurosfaire.prd.fr · The complex linguistic abilities of humans are unique, but how we...

The complex linguistic abilities ofhumans are unique, but how we acquire

our language skills during early develop-ment is far from fully understood. Improvingour understanding is important as a basicresearch issue that may help us understandlanguage disabilities, and may improveartificial language recognition systems.

The CALACEI project is examining this issueas part of the NEST PATHFINDER initiativeon ‘What it means to be human’. After all,what is more characteristically human thanour language faculty?

To understand the uniqueness of humanlanguage, the project is designed to gainknowledge of how human infants acquiresyntax, and how a child learns to handlethe properties of a specific language. Thisincludes investigating the anatomical andphysiological processes in the infant brain,and relating them to the adult brain.

The challenge facing CALACEI straddlesmany disciplines, and the project partnersare a diverse collection of experts in psych-ology, physiology, linguistics, physics,medicine and the functional imaging ofthe brain. This range of expertise comesfrom the International School for AdvancedStudies, in Italy, The Berlin NeuroImaging

We spend much of our lives

talking and listening. Being

human involves communicat-

ing, but how do we learn to

do it? The CALACEI project

is probing this fundamental

mystery. Partners ranging from

linguists to physicists will

tackle practical and theoretical

barriers to conduct studies of

newborns and infants that have

not been possible until recently.

The project could reveal much

about how we learn to use

language, and may point the

way to applications in medicine

and artificial intelligence.

Center in Germany, The Max Planck Instituteof Human Cognitive and Brain Science, inGermany, and The Centre for Brain andCognitive Development in the UK.

Viewing the infant brain

In recent years, several methods have beendeveloped to visualise which parts of thebrain are most active during specific tasks.Some of these brain imaging processes,especially functional near-infrared opticaltopography and electroencephalography,will be used for a range of studies in thisproject. For example, one approach willexplore how the brains of newborn babiesand infants respond to languages thatdiffer in their rhythmic structure. Anotherwill look at the response of the infant andadult brain to vowels and consonants.Some pioneering work with newborninfants will investigate the extent to whichthey can distinguish between differentkinds of syllables.

Parts of the project will employ a form ofcomputing known as neural network mod-elling, to represent learning processes ofthe brain computationally.

One crucial aspect of CALACEI is to developthe practical aspects of the imaging methods

Looking into talking

!

C AL ACE I

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The project is designed to gain knowledge of how human infants acquire syntax, and how a child learns to handle the properties of a specific language. W H A T I T M E A N S T O B E H U M A N

What is more characteristically human than our language faculty?

refute or refine a variety of hypothesesabout the precise way in which very younghuman infants acquire language skills.With fundamental research it is not possi-ble to promise specific applications at such

an early stage. It is thenature of basic science,however, that it leadson to practical and oftenunpredictable applica-tions in the future.

Problems in learninghow to use language are both common-place, and very debilitating. The more welearn about how this uniquely humanprocess is acquired, the greater are thechances that we will find new ways tounderstand what causes these (develop-ment) problems and how to correct them.

The research also addresses the challengesfacing a multilingual society, such as theEuropean Union. Decisions about teachingseveral languages at different ages canbe made with more confidence whenthe processes underpinning languageacquisition are properly understood.

to make it easier to gain more useful infor-mation from newborn babies and infants.Little functional imaging has been done withvery young infants due to the absence ofsuitable methods. Very high safety standardsmust obviously be metin any such work, andthe experimenters haveto learn how to copewith the low level ofco-operation of theiryoung subjects. Theproject is going toexplore methods to gather data fromhealthy babies in a non-invasive andecologically valid fashion. The partnerswill develop some new techniques andimprove the existing ones for gatheringdata from infants, and will make thistechnology available to other researchersworking in this field.

Theory to build on

The CALACEI project is addressing funda-mental theoretical issues about what itmeans to be human. Its end results in termsof theoretical advancement should confirm,

AT A GLANCE

Official titleUniversal and Specific Properties of a Uniquely Human Competence Tools to study language acquisition in earlyinfancy: Brain and Behavioural Studies

CoordinatorItaly: International School for AdvancedStudies, Cognitive Neuroscience, SISSA

Partners• Germany: Berlin NeuroImaging Center• Germany: Max Planck Institute of

Human Cognitive and Brain Science• United Kingdom: Centre for Brain and

Cognitive Development

Further informationProf. Jacques MehlerInternational School for Advanced Studies,Cognitive Neuroscience, SISSAvia Beirut 4Trieste 34014ItalyFax: +39 040 378 7615Email: [email protected]

Duration36 months

Project Cost€ 1 498 000

EU Funding€ 1 498 000

Project referenceContract No 012778 (NEST)

Web: http://www.cordis.lu/nest

What is more charac-teristically humanthan our ability tospeak?

C AL ACE I

© European Commission, 2005

The Commission accepts no responsibility or liability whatsoeverwith regard to the information presented in this document.

T he ‘Evolution, development and inten-tional control of imitation’ (EDICI) project

is investigating imitation, a fundamentalaspect of human behaviour, as part of thewide-ranging NEST PATHFINDER initiativeon ‘What it means to be human’.The specific objectives of the project areto answer the following questions: 1) What are the evolutionary origins of thepotential to imitate? 2) What types of experience enhance thepotential for imitation? 3) How does intentional control of imita-tion change in the course of human devel-opment? 4) Do the neuro-cognitive mechanismsthat distinguish self from others play akey role in intentional control of humanimitative performance? and 5) Is intentional control of imitative per-formance uniquely human?EDICI is a highly interdisciplinary project.It combines methods and insights fromthe fields of ethology, evolutionary biol-ogy, neuro-physiology, neuro-psychol-ogy, and comparative, developmental andexperimental psychology. The partnershipincludes leading international experts inthese areas, from academic research groupsin Austria, the United Kingdom, Germanyand Hungary.The project is highly original in terms ofboth its theoretical and methodological

Our capacity for imitation

underpins the learning of

language, technical skills,

socialisation, and culture.

The dominant North American

model says imitation is innate

– present at birth rather than

established by conditioning

or learning. The EDICI pro-

ject is testing an alternative

European model that incor-

porates evolutionary, devel-

opmental and cultural inputs

to imitation. It may reveal new

ways to help people with

impaired imitative ability, and

will assist in the design of

training programmes.

approaches. It is the first study on imita-tion to compare humans, not only withother primates, but also with birds anddogs. It is also the first to coordinate inves-tigation of non-human animals, children,healthy adults and neurological patients,and the first to make use of techniquesfrom ethology and evolutionary biology,as well as from psychology and neuro-physiology.

Challenging the American model

Europe is the home of evolutionary theory,ethology and genetic epistemology, andwas the site of the earliest scientificresearch on imitation. Despite this his-torical engagement, however, under-standing of imitation in humans is cur-rently dominated by a North Americanmodel, which claims that imitation is aninnate ability. The EDICI project builds onEurope’s historical strengths in the fieldto test a distinctively European model ofimitation, using world-class Europeanfacilities and expertise. The key featuresof this European model are that it incor-porates the significance of evolutionary,developmental and cultural factors intoour understanding of imitation.The latest and most precise behaviouraland imaging techniques are being usedto test samples of non-human animals,

Learning by imitation

EDICI

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The potential for imitation has evolved in a wide range of species. W H A T I T M E A N S T O B E H U M A N

Imitation is a key par of growing up.

Break-throughs with wide applications

The project partners expect to make majorbreakthroughs in understanding the evo-lutionary, developmental, cognitive andneurological bases of imitation. In keep-ing with the often wide-ranging conse-quences of basic science, they also

believe that their inte-grative approach willhave a broader impacton model-building inevolutionary psych-ology and cognitiveneuroscience.In contrast with theNorth American con-ception, the Europeanmodel of imitationdeveloped by this pro-ject emphasises the

role of experience in the development ofimitation. For this reason, the work willcontribute to the design of social and tech-nological skills training programmes, andto new ways to help children and adultswith impairments in imitative ability.

infants, healthy adults and neurologicalpatients. Marmosets, social birds anddomesticated dogs have been selectedas the non-human subjects of the studybecause they are each related to humansin a different way.Alongside many other techniques, func-tional magnetic resonance imaging isbeing used with healthy adults to investi-gate the types of experi-ence that enhance imi-tative potential, andto identify the way inwhich localised activ-ity within the brain isrelated to imitationand activities that donot involve imitation.One key target of thework with humans is tomeasure the strengthof an individual’s poten-tial to imitate, and their capacity to regu-late the expression of this potential inovert imitative performance. These areexamples of aspects of imitation whichcould reveal that imitation is more subtleand complex than just an innate ability.

AT A GLANCE

Official titleEvolution, Development and Intentional Control of Imitation

CoordinatorAustria: University of Vienna

Partners• Germany: Max Planck Institute of

Human Cognitive and Brain Sciences• Hungary: Institute for Psychological

Research of the Hungarian Academy of Sciences

• UK: University College London

Further informationProf. Ludwig HuberDepartment for Behavior, Neurobiology and CognitionUniversity of ViennaAlthanstrasse 14A-1090 ViennaFax: +43 1 4277 54509E-mail: [email protected]

Duration36 months

Project Cost€1 344 326

EU Funding€1 344 326



The EDICI team’s inte-grative approach willhave a broader impacton model-buildingin evolutionary psych-ology and cognitiveneuroscience.

EDICI


The Commission accepts no responsibility or liability whatso-ever with regard to the information presented in this document.

The FAR project: From associations torules in the development of concepts,

is studying how humans and other specieslearn concepts, as part of the NEST initiativeon ‘What it means to be human’. The projectbrings together five teams of researchersfrom the United Kingdom, France, the Nether-lands and Greece. It is harnessing expertisein animal cognition and evolutionary theory,infant and child development, adult conceptlearning, neuro-imaging, social psychology,neural network modelling, and statisticalmodelling.The partners are looking specifically at thetransition from associative cognition (basedon similarities) to rule-based cognition, inthe context of learning concepts – the pri-mary cognitive means by which we organ-ise things in the world. Any species lackingthis ability would quickly become extinct. Inhumans, however, rule-based cognitionreaches a level of complexity that makesour language, logic and other unique cog-nitive powers possible.

Six objectives

The first objective of the project is to developa computational model of rule-based con-cept learning, both within individuals andthroughout the course of evolution. Neuralnetwork computer simulations are being

What makes humans different

from other animals? Obvious

differences include our ability

for complex communication

using language and our use of

logic and mathematics for

reasoning. Researchers would

add our ability to identify

abstract relationships that go

beyond clearly perceived

similarities. These aspects of

human cognition are thought

to be based on rules, so the

FAR project is examining

the origin and mechanism

of rule-based systems. The

results may be used in

education, medicine and

artificial intelligence.

used to explore alternative evolutionaryscenarios.A second goal is to establish statisticalrules to enable rigorous discriminationbetween rule-based and similarity-basedclassification behaviours. This approachis designed to overcome problems experi-enced with traditional methods based onsimply talking to participants. Theseexclude non-verbal factors and rely onquestionable assumptions about the accu-racy of participants’ reports.Next, the partners are trying to establishthe conditions under which human adultsshow rule-based or similarity-based con-cept learning. There are competing theo-ries in this area, and the work of FAR willhelp to identify the most valid approach.Objective four looks at the emergence ofrule-based as opposed to similarity-basedconcept learning during evolution, by analy-sis of different species. This will establishwhether differences between previousresults in humans and birds are due tomammal/bird or human/non-human dif-ferences. It will also reveal whetherhuman/non-human differences are due tohuman use of language.The fifth objective is examining the emer-gence of rule-based learning in humans asthey make the transition from infancy toadulthood. Studies of infants and children

Rules for humanity

FAR

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Neural imaging will be used to investigate rule-based cognitive reasoning in humans.W H A T I T M E A N S T O B E H U M A N

Computational models developed by the project should explain the differences in cognitive mechanisms.

pressures cause the emergence of differentcognitive systems.From a more practical point of view, theproject should determine the best way topresent visual, auditory and linguistic infor-mation to ensure that people store and

retain this information.This may have importanteducational implications– after all, understand-ing how best to presentand organise materialto optimise learning isof crucial relevance tosociety as a whole. Understanding the neuralbasis of concept learn-ing may also suggest

better medical and remedial strategiesfor treating semantic disorders. And in tech-nology, understanding when rule or asso-ciation use is optimal, from a human per-spective, may improve the design of roboticand artificial intelligence applicationsintended to mimic human functions.

are being used to clarify and extend recentresults in this area.Finally, the partners want to use moderntechniques such as neuro-imaging to learnabout the neural basis of rule-based conceptlearning in humans. They want to knowwhat is actually goingon in the brain.

Hopes and aspirations

The FAR project is basicscience, but the part-ners have some specifichopes for the theoret-ical and practical ben-efits it may bring. Theyexpect to clarify whether rule-governedcognition is indeed uniquely human,as is commonly believed. They also hopeto identify the conditions under whichhuman adults rely on rules to learn con-cepts. And the computational models theydevelop should reveal plausible mech-anisms for how changing environmental

AT A GLANCE

Official titleFrom Associations to Rules in the Development of Concepts

CoordinatorUnited Kingdom: Birkbeck, University of London

Partners• France: Université de Bourgogne• Greece: University of Crete• Netherlands: University of Amsterdam• United Kingdom: University of Exeter

Further informationDr Denis MareschalCentre for Brain and Cognitive Development,School of PsychologyBirkbeck, University of LondonMalet StreetLondon WC1E 7HX – UKFax: + 44 2076316312Email: [email protected]

Duration36 months





Understanding howbest to present andorganise material tooptimise learning isof crucial relevanceto society as a whole.



FAR

T he Neurocom project is part of theNEST-PATHFINDER initiative ‘What it

means to be human’. Its focus is languageand communication, two eminently humanabilities with roots in both early child devel-opment and the evolutionary origins of ourspecies. In Neurocom, experts from a widerange of fields have joined forces: linguists,psychologists, ethologists, neuroscien-tists, and cognitive scientists. Their aim isto distinguish, within human communica-tion channels, major human-specific com-ponents and the neural circuitry thatsupports them in the cortex of the humanbrain.Aware of the progress made in linguisticsand cognitive science, thanks to the inte-gration of developmental data and inter-species comparisons at the behaviourallevel, the project partners predict a furthergreat leap forward once the neural level iswoven into the picture. Today, advancesin neuro-imaging are providing powerfultools for visualising the brain as it per-forms complex functions such as learning,or making sense of someone’s utterancesor actions. The Neurocom partners areeager to exploit these tools and to beginintegrating all that is known about lan-guage and communication, as it relates to

Language and communication

are essential human faculties,

but what are their uniquely

human components? To high-

light these elements while

exploring the functional archi-

tecture of the human brain,

the Neurocom project will

combine behavioural testing

with cutting-edge neuro-imag-

ing. The project’s originality

lies in the integration of the

biological and cognitive levels

in a developmental and evolu-

tionary perspective. Its impact

may extend to many fields, from

human medicine to robotics.

the emergence of the human species andto individual human development.

Comparing and integrating

To tackle the developmental and evolution-ary aspects of human language and com-munication, the Neurocom consortiumcompares human adults with babies, andhumans with non-human primates (maca-ques). Teams pursue the following specificobjectives: to map the neural substrates ofthree communication channels (speech,calls, and gestures); to find the neural sub-strate of speaker invariance; to study under-standing of intention in humans and babies,and investigate monkeys’ interpretation ofactions; to study communicative referen-tial cues (gaze shift and pointing), theirsubstrate, and their role in learning newwords; to investigate the neural processingof hierarchical structures in syntax and theneural substrate involved in learning anartificial grammar.The work combines behavioural testing withneuro-imaging. Many experiments involvemapping and monitoring brain regions thatbecome activated and – possibly – showadaptation in subjects placed in a learningcontext (with or without communicative

What is human in humancommunication?

N E U ROCOM

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Not all aspects of communication are unique to humans.W H A T I T M E A N S T O B E H U M A N

New neuro-imaging techniques can develop understanding of brain function when carrying out complex tasks.

knowledge available about cortical functionin this non-human primate.The knowledge gained within Neurocomwill have a major impact on our under-

standing of neuronalchanges in brain dis-eases, which represent35% of the disease bur-den in Europe. In addi-tion, the project is likelyto pave the way towardsusing fMRI in monkeysto explore the interac-tions of potential drugswith the neural sub-strates of cognitive abil-ities. In the field of fMRI,

Neurocom will yield technological improve-ments contributing to the further devel-opment of this technique as a diagnostictool.Other fields also stand to benefit fromthe results of this project. One of them iseducation, thanks to the project’s focus ondevelopment and learning. And Neurocom’simpact is likely to extend still further, toengineering fields such as speech recogni-tion, image understanding, and robotics.

referential cues) or exposed to speech, calls,gestures, or videotaped action sequences.The neuro-imaging techniques used forthis approach include functional magneticimaging (fMRI, per-formed on all categor-ies of subjects), near-infrared spectroscopy(on babies), and single-neuron recording (onmonkeys).

Impact andprospects

Neurocom will yield,for the first time, aninformed view of which major componentsof language are truly unique to humans. Itwill generate new knowledge on the func-tional architecture of the human cortex,and in some cases it will shed light onneuronal operations performed in corticalregions that ‘light up’ in imaging experi-ments. By highlighting the relationshipbetween the human cortex and that ofthe macaque, the work will make it pos-sible to integrate into human studies all the

AT A GLANCE

Official titleNeural origins of language and communication

CoordinatorBelgium: Katholieke Universiteit Leuven

Partners• France: Ecole des Hautes Etudes

en Sciences sociales• Italy: Universita degli Studi di Parma• France: Institut national de la Santé

et de la Recherche médicale• Hungary: Institute for Psychological

Research of the Hungarian Academy of Sciences

Further informationProf. Guy OrbanLaboratory of Neuro- and Psychophysiology,Katholieke Universiteit LeuvenCampus Gasthuisberg, Herestraat 49B-3000 LeuvenFax: +32 16 345 993E-mail: [email protected]

Duration36 months





Neurocom will yield,for the first time, an informed view ofwhich major compo-nents of languageare truly unique tohumans.

N E U ROCOM



Our advanced ability to think, to expressemotions and to influence the behav-

iour of those around us is part of whatmakes the human mind unique. Thesehigher cognitive functions have evolvedthrough major changes in the structure,functional complexity and size of the brainat different points along the evolutionarytree that links us to monkeys and apes.Identifying the molecular basis for thesechanges is key to understanding whichcognitive abilities, and their correspondinggenes, are unique to humans.The NEST PKB140404 project, part of thePATHFINDER initiative to investigate ‘Whatit means to be human’, will use an inte-grated approach, bridging cognitive neuro-science and molecular evolution, to probethe differences between the brains ofhumans and their closest relatives, theapes. The consortium’s multidisciplinaryresearch teams, combining skills in molecu-lar and evolutionary biology, bioinfor-matics, clinical psychiatry and neuro-science, aim to reconstruct the historyof the evolutionary changes that led tothe emergence of the human mind as it istoday. In a three-pronged approach, eachteam will look for turning points in thedevelopment of the human mind by

Studying the evolutionary

pathways that have led to the

emergence of the human mind

provides a fascinating insight

into the history of what has

made – and what makes us –

unique in the animal world.

A NEST project aims to pin-

point the molecular basis

and evolutionary origins of

our cognitive abilities, by

comparing humans and apes.

Through an ambitious attempt

to progressively introduce

human cognition genes into

transgenic mice, the consor-

tium plans to explore the

‘birth’ of the human mind.

studying different stages in the molecularprocess.

Pinpointing molecular change

The Swiss group will search for recentlyevolved genes that have arisen throughretroposition – a type of gene duplica-tion – and that are associated with cogni-tive abilities. A burst of retropositionstarted around the time when the groupcomprising humans, apes and Old Worldmonkeys branched off on the evolutionarytree. Some of the new genes created bythis evolutionary process enabled newneurological functions and resulted,through positive selection, in the devel-opment of higher cognitive abilities.

The German group will use advancedmicro-array technology to scan genesshared by humans and apes to look forthose expressed differently in eachspecies’ brain. As some differences inexpression can lead to changes in genefunction, the project’s challenge is to iden-tify which of these differences are asso-ciated with changes in cognitive abilityand whether they could be responsiblefor the human brain’s uniqueness.

Exploring the origins of the human mind

Common parts of our evolutionary pathway means we can learn much about our cognitive abilities from studying apes. W H A T I T M E A N S T O B E H U M A N

PKB140404

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Identifying dysfunctional genes which cause brain diseases will help develop treatments.

and set us apart from other species. Animportant step in validating the project’sfindings will be confirming the functionof the candidate human cognition genesidentified by the three complementaryapproaches. To do this, the consortium

will carry out in vivostudies using trans-genic mice carrying thehuman gene and com-pare their resultingphenotypes with micecarrying an equivalentgene from the apegenome.In the long term, theyhope to show that replac-ing a sufficiently largenumber of mouse genes

with their human counterparts will lead toaltered behaviour in the mice and providefurther insights into genetically regulatedhuman cognitive faculties.This ambitious reconstruction of the evo-lutionary history of human cognitive abil-ities will set the standards for new work inthe area. The consortium will explore newhorizons in cognitive science and shouldmake an important contribution to solvingthe enigma of human nature.

A third approach, by the British group,will identify which genes dysfunction inhuman diseases like schizophrenia, bycomparing post-mortem brain samplestaken from schizophrenia patients withthose from a healthy control group, and with those fromthe correspondingregion of the apebrain. Schizophreniais characterised by areduced ability tounderstand and manipu-late the mental repre-sentations of others.As this and other cog-nitive abilities affectedby the disease are lessdeveloped or not pres-ent in apes, it is likely that the humangenes associated with schizophrenia playa pivotal role in human cognition.

Setting us apart

This project has the potential to unravelseveral of the mysteries surrounding thebirth of the human mind, by revealing anddating some of the genetic changes thathave contributed to our shared heritage

AT A GLANCE

Official titleMolecular evolution of human cognition

CoordinatorGermany: Max Planck Institute for Evolutionary Anthropology

Partners• Switzerland: Center for Integrative

Genomics• UK: Babraham Institute

Further informationProf. Svante PääboMax Planck Institute for EvolutionaryAnthropologyDepartment of Evolutionary GeneticsDeutscher Platz 6D-04103 LeipzigFax: +49 341 3550 555E-mail: [email protected]

Duration36 months





The consortium plansto explore the ‘birth’of the human mind,through an ambitiousattempt to progres-sively introduce humancognition genes intotransgenic mice.

PKB140404



Many of the advances made byhumankind have relied on a sophis-

ticated ability to share knowledge. Theversatility of human communication, andin particular the capacity to communicateverbally and non-verbally about things in theenvironment, is one of the unique featuresof the human species. However, a widevariety of other animals, in groups as evo-lutionarily distant as bees, dolphins anddogs, also exhibit some form of this refer-ential communication at lower levels ofsophistication. Scientists are now propos-ing that human referential communicationis not a single ability but a complex functionresulting from the integration of a variety ofskills and capacities with different evolu-tionary origins.Refcom, part of the PATHFINDER initiativeto investigate ‘What it means to be human’,is a highly ambitious multidisciplinary pro-ject, associating eight European laboratories,which aims to trace these evolutionaryorigins. By comparing referential commu-nication skills in diverse animal species,in the wild and in captivity, with those ofchildren, they hope to contribute to a com-prehensive understanding of the origins ofthis key cognitive ability.

The capacity to communicate

verbally and non-verbally

about things in the environ-

ment is a key element of human

cognitive prowess. To under-

stand which aspects of this

skill are uniquely human, the

Refcom project will compare

the complexity of messages

conveyed by different species

– from a dolphin’s whistle to a

gorilla’s gesture to a child’s

words – in an unprecedented

attempt to trace the different

evolutionary origins of refer-

ential communication across

the animal world.

From gesture to word

The strongest evidence for referential com-munication in non-human primates comesfrom wild monkeys which use various typesof predator-specific alarm calls. Somespecies are able to encode aspects such asthe severity of an attack and interpret themeaning of other primate and non-primatealarm calls. Interestingly, there is much lessevidence for vocalised referential commu-nication in our closer relatives, the apes.One possible explanation is that their limitedability to modify their voices has led them tospecialise in a referential communicationbased on gesturing. By looking for evidenceof referential signals in wild monkey callsand exploring the communicative functionof vocal and gestural repertoires in bonobosand gorillas, the Refcom project aims to testthe diversity of communication skills thathave evolved in different primate groups, andthat may underlie our own abilities.To answer questions about what sort ofsocial and environmental challenges mayhave caused referential communication toarise independently on other branches ofthe evolutionary tree, the consortium willalso study the abilities of non-primatespecies – dolphins, parrots and dogs – to

Comparing the sharing ofknowledge across species

Refcom will study the different forms of communicating complex messages in species.© Miguel A. Gomez

R E FCOM

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W H A T I T M E A N S T O B E H U M A N

Complex messages may also be transmitted within non-primate species.© Adam Miklosi & Eniko Kubinyi

cation within an evolutionary framework.Its unprecedented data collection from adiverse set of animal species, using commonmethodological principles and a unifiedconceptual framework, will provide a major

opportunity for Europeanresearchers to under-stand how our uniquecognitive abilities fitinto the schema ofadaptive evolutionaryhistory. The consortiumalso hopes to generatemore applied outcomesthrough a better under-standing of cognitive

impairments such as autism, leading to thedevelopment of new tools for improveddiagnosis and treatment.Through its cross-disciplinary approach,the consortium will forge new links andaddress persistent conceptual barriers thathave prevented progress in the past. Theimportant contributions of two Hungarianinstitutions will help to integrate them intoa wider European framework for researchat a crucial stage in their country’s incorpor-ation into the EU.

communicate referentially using both nat-ural signals and those learnt through humancontact.One of the project’s key challenges will beto identify what features make humanreferential communica-tion unique, by com-paring the perform-ances of children withapes, dogs and parrotswhen faced with anidentical task requiringreferential skills. Theinclusion of autistic chil-dren in this exercisewill help to determinewhich communication skills are impairedin this debilitating condition.To complete the cross-disciplinary approach,consortium members will also explore thegenetic and neural basis for referential com-munication in the dog.

A unified conceptual framework

The Refcom project aims to provide themost comprehensive analysis to date ofthe components of referential communi-

AT A GLANCE

Official titleOrigins of Referential Communication

CoordinatorUK: University of St Andrews

Partners• France: University Paris X• Germany: Max Planck Institute

for Evolutionary Anthropology• Hungary: Eötvös University• Hungary: Semmelweis University• Switzerland: Swiss Academy of Sciences• UK: University College London• UK: Reading University

Further informationDr Juan Carlos Gómez School of Psychology, University of StAndrews South Street w/nSt. Andrews KY16 9JUUKFax: +44 1334 463042E-mail: [email protected]

Duration36 months





The Refcom projectaims to test the diver-sity of communicationskills that have evolvedin different animalgroups.

R E FCOM



T he question of what makes us humanhas occupied the minds of philosophers

and scientists across the centuries. Recentadvances in genome sequencing have madethe debate even more pertinent, as we nowknow that the quantitative genetic differ-ences between us and many other mam-malian, particularly primate, species, areextremely small. The SEDSU project aims toprovide one answer by demonstrating thatwhat characterises humans is their advancedability to engage in sign use.By studying the relationship between fivedistinct cognitive domains and their rolesin the development of sign use and lan-guage, the project team will show how signuse changes, both with the evolutionarydevelopment of species and within the life-stage development of individuals. The fivedomains – perception and categorisation;iconicity and pictures; spatial conceptual-isation and metaphor; imitation and mimesis;and inter-subjectivity and conventions – areeach characterised by a developmentalprofile linked to a distinct semiotic process,such as the use of pictorial representationsor gesturing. Using an interdisciplinaryapproach and a specially developed set ofanalytical tools, the team hopes to demon-strate that the transition from one devel-opmental stage to another can be explainedby the acquisition of a cognitive ability to

An advanced ability to use and

interpret signs is one of the

characteristic features of human

beings, setting us apart from

the rest of the animal world.

Through the SEDSU project,

European specialists in human

and primate cognition will

study how sign use changes

with the evolutionary devel-

opment of species and within

individual development. A

better understanding of the

different factors underlying

sign acquisition in humans will

have important implications

for social and educational

policies.

use more advanced forms of signs, and todifferentiate between the sign itself – suchas a word or an abstract symbol – and whatit represents.

Multi-dimensional intelligence

The human brain and its mental facultieshave been influenced throughout theirevolution by a wide range of selection pres-sures including physiological, cultural andenvironmental factors. Non-human primates,though very close to humans in geneticterms, have experienced differing selec-tion pressures through evolution and thisis reflected in their varying capacities touse signs. The SEDSU project brings togetherthree major primate laboratories along withthree laboratories with expertise in thestudy of the origins of higher cognitiveprocesses in humans.Cognitive and developmental psychologistswill work alongside primatologists, lin-guists, anthropologists, philosophers andsemioticians in a comparative analysis ofsign use in humans, in monkeys and inapes. The influence of cross-cultural selec-tion pressures in humans will be studiedthrough comparative studies of the fivecognitive domains within human popula-tions in Namibia, Amazonia, Thailand andIndia. In this way the project hopes to

Signing up to be human

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Recognition and understanding of signs has evolved differently in different primate species.W H A T I T M E A N S T O B E H U M A N

A key characteristic in humans is the ability both to separate the meaning of a sign from its identifiable form.

policies concerning child-rearing andeducational practices, particularly at thepre-school level, in both developing andmore developed countries. The project also

has implications for themore clinical aspects ofsocial and educationalpolicy, and will informthe debate on the needfor special educationalprovision for childrenwith autism or impairedhearing.Ultimately, the SEDSUproject team hopes thatits findings, based onsound empirical stud-ies, will contribute to are-evaluation of the cur-rent theoretical basisof semiotics and pro-

vide the foundations for a new coherenttheory of semiotic development. Whilstthe project does not explicitly target theevolution of language, it should alsoinform this area of debate because of thenecessary continuum between sign useand evolved language.

explore human universality and culturalvariation.Whilst our species carries with it the his-tory of its evolution, each person’s mind isthe unique creation ofa process of individualdevelopment result-ing from interactionsbetween genetic, envi-ronmental and socio-cultural factors. To cap-ture the influence ofthese factors in thedevelopment of signuse in humans, theSEDSU team will studygroups of children atdifferent stages ofdevelopment, as wellas those affected byautism and deafnesswho may use and acquire sign use indifferent ways.

Towards a new theory of semiotics

By comparing the development of signuse under different social and culturalsettings, the SEDSU project has the poten-tial to make important contributions to

AT A GLANCE

Official titleStages in the Evolution and Development of Sign Use

CoordinatorUK: Goldsmiths’ College, London

Partners• France: INCM-CNRS• Germany: Max Planck Institute

for Evolutionary Anthropology• Italy: ISTC-CNR• Sweden: Lund University• UK: University of Portsmouth

Further informationProf. Jules DavidoffGoldsmiths’ CollegeCentre for Cognition, Computation and Culture Lewisham Way, New CrossLondon SE14 6NW - UKFax: +44 20 7919 7873E-mail: [email protected]

Duration36 months





The team hopes todemonstrate that thetransition from onedevelopmental stageto another can beexplained by theacquisition of a cog-nitive ability to usemore advanced formsof signs.

S EDS U



Finding your way home, rememberingwhere you left the car keys or directing

someone to the nearest hospital are exam-ples of highly complex cognitive tasks basedon spatial memory and orientation. Withoutthese functions, navigating through dailylife would be impossible. Our ability toconstruct spatial representations of theoutside world, and to store them in ourmemory is likely to underlie many otherhigher cognitive functions in humans, suchas decision-making and planning.Many other animals possess the ability tonavigate around their environment, butthere are certain higher-order features of thehuman system, such as the ability to com-municate spatial information verbally, whichare uniquely human. The Wayfinding projectwill contribute to the NEST PATHFINDERinitiative to investigate ‘What it means to behuman’, by exploring the particularities of thecognitive organisation of spatial memoryand orientation in humans from an evolu-tionary perspective. This European consor-tium, bringing together six laboratoriesworking in psychology, physiology, biology,neuroscience, anthropology and artificialintelligence, aims to map differences in spa-tial ability, both between humans and otherspecies, and within human populations.

Spatial orientation and memory

are key functions that help us

to operate in a complex world.

A European research consor-

tium will retrace the evolu-

tionary history of these

cognitive skills and show

how individuals adapt their

navigational strategies to cir-

cumstance. A more in-depth

understanding of how humans

make sense of space will pro-

vide invaluable information

for environmental planning

and design, and lead to

improved solutions for people

with impaired spatial abilities.

Taking a perspective

How we perceive and remember the loca-tions of objects is multi-faceted and dependson circumstances. In their most advanced,abstract form, our spatial representationshelp us to create mental images of whatother eyes might see from a differentperspective. But it is likely that the humancognitive system has also preserved theevolutionary history of spatial abilitiesand may at times rely on much simplernavigational mechanisms.The Wayfinding project will explore thesedifferent mechanisms and attempt to maptheir evolutionary hierarchy and neural basis,using a combination of experimental cog-nitive tests and neuro-imaging techniquesin rats, monkeys and humans. Once theirplace in the hierarchy is confirmed, theproject will concentrate on those mech-anisms considered uniquely human, such asperspective taking.Intriguing evidence suggests that humanscan shift from one navigational strategyto another according to requirements.Comparing the ways healthy volunteershandle spatial tasks with those sufferingfrom visual or selective neurological impair-ments will provide researchers with a

Understanding humannavigation

Human understanding of spatial location sets us apart from other species.

W AYF I N DI NG

W H A T I T M E A N S T O B E H U M A N

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Neural imaging will help develop understanding of human spatial awareness.

A better understanding of how the humannavigational system works has importantsocial and practical implications, too.Elementary educational programmes willbe one area to benefit from a greater insightinto the development of children’s visual

and spatial abilities.Likewise, the projectoutcomes should help tofind solutions for thoseconfronted with prob-lems in spatial orienta-tion – the elderly, the visu-ally impaired, and patientssuffering from brain dam-age or Alzheimer’s dis-ease – tocope better witheveryday life.

Future technical applications will includeartificial navigation systems and virtualreality tools calibrated to take into accountvariations in human performance. On abroader scale, the consortium hopes that theproject will also yield invaluable knowledgefor city planners, architects and designers,making it easier for us to find our waythrough space, whether in the corridors ofa new building or in the virtual labyrinth ofa computer interface.

fascinating insight into which parts of thebrain process the different navigationalmechanisms, and whether an impairmentaffecting one mechanism triggers a shiftto an alternative strategy. The use of func-tional neuro-imaging techniques will helpto pinpoint the neuralcircuitry activated byverbal and visual inputsduring the differenttasks.To complete their over-view of how spatialmemory and orienta-tion have evolved inhumans, the consortiummembers will study theinfluence of gender, ageand culture on performance in certainspatially related tasks.

Towards design for navigation

This project will make a significant scientificcontribution to the quest to understandhow different elements of the human cog-nitive system are organised and functiontogether.

AT A GLANCE

Official titleFinding your way in the world - on the neuro-cognitive basis of spatial memory and orientation in humans

CoordinatorThe Netherlands: Utrecht University

Partners• Germany: Max Planck Institute for

Biological Cybernetics, Tübingen• UK: University College London• France: LIMSI CNRS, Orsay• France: Collège de France, CNRS, Paris• Italy: Fondazione Santa Lucia,

University of Rome

Further informationProf. Dr Albert PostmaHelmholtz Institute of the Social ScienceFaculty, Utrecht UniversityHeidelberglaan 23584 CS UtrechtThe NetherlandsFax: +31 30 253 4511E-mail: [email protected]

Duration36 months





A better understand-ing of how the humannavigational systemworks has enormoussocial and practicalimplications.

W AYF I N DI NG



The kaleidoscope of colours, shapesand sizes that is found in the natural

world is clear evidence of the complexityof living organisms. This complexity hasbeen driven by evolution over millionsof years and many creatures show extra-ordinary adaptations that have given theirspecies a competitive edge in the gameof life.

The BIOPHOT project aims to study thisnatural complexity in the specific case ofhow creatures interact with the electro-magnetic spectrum, particularly visiblelight but also the neighbouring infra-redand ultraviolet regions, to enhance theirsurvival and reproduction chances. A vastrange of optimised natural optical devicesand materials have evolved that are usedby various organisms in a wide varietyof complex tasks ranging from sexualsignalling to thermal management.

The project team from Belgium, Hungary,France and the United Kingdom will inves-tigate these natural designs, using a broadperspective and a number of complementarydisciplines. This complex, multidiscip-linary approach will involve high-resolutionstructural and physical characterisation,

The natural world shows a huge

diversity of colour and form.

Elucidating the mechanisms

by which these colours and

contrasts are achieved through

the interaction of light with

an organism’s bio-structure

and how these structures

have evolved over time is an

extremely complex task. How-

ever, success would significantly

enhance our understanding of

nature and behaviour, as well

as offering us design models

for new materials with novel

properties that have been

‘tested and approved’ by

nature.

evolutionary data in terms of both timeand geography, significant modellingactivities and the study of the behaviour ofliving organisms.

Evolutionary design

The combination of techniques will give adeep and detailed insight both of the evo-lutionary processes that have optimised acertain structure for a particular task andalso the manner in which different butrelated structures exhibit altered properties.The physical characterisation will focusaround a combination of optical andelectron microscopy techniques that willgive new knowledge of the micro- andnano-morphology of specific bio-organismswhich display unique and remarkable light-scattering ability. This structural informationwill be related to precise measurements ofthe light-filtering function using micrometer-resolved spectrophotometric and thermalmeasurements.

Extensive measurements of the reflection,absorption and polarisation changes asa function of the frequency and angle ofincidence of electromagnetic radiation willbe made. Extensive numerical simulation

Natural nano-design is a beauty to behold

B IOPHOT

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The study of the bio-organism in its environment at different evolutionary epochs requiresanalysis of a very large number of interactions and dependencies. © Thomas JonesTAC K L I N G CO M P L E X I T Y I N S C I E N C E

The kaleidoscope of colours, shapes and sizes that is found in the natural world is clear evidence of the complexity of living organisms.

Complexity is not an easy phenomenon toexplain, however one of its characteristicsis the emergence of new patterns orbehaviours that transcend the individualcharacteristics of component units. TheNEST PATHFINDER initiative on under-standing human complexity, of whichBIOPHOT is part, looks to develop andtransfer solutions and understanding ofreal-world complexity from one area ofscience to another. This builds both cross-national and cross-disciplinary links

that enhance Europeanresearch ability.

The greater under-standing that BIOPHOTwill bring to the hier-archical assemblies ofnatural structural ele-ments over length-scalesof varying orders of

magnitude will provide guidance for thedesign of new synthetic structures. Theimprovement of simulation and modellingtools can significantly reduce the devel-opment costs for man-made nanostruc-tured materials with novel photonic prop-erties. The hope is that a significant‘technology transfer’ from natural biologyto synthetic materials science can beachieved.

will also be employed using the parallelcomputing system at the University ofNamur. As a bonus, this will provide anopportunity to test the ‘grid-computing’model that is an essential issue for a numberof European initiatives.

The target organisms will also be studiedin terms of their ecological and pheno-logical (the timing of various biologicalphases) history and closely related orcompeting species will be identified forfuture examination.Cross-disciplinary dis-cussions, including theuse of paleontologicaldata where available,will help to determinewhether an organism’soptical scattering mech-anisms give an evolu-tionary advantage thatcan explain the survival of the species in itsecosystem.

Complex interactions

The study of the bio-organism in its envir-onment at different evolutionary epochsrequires analysis of a very large number ofinteractions and dependencies. Similarly,the experimental and theoretical aspectsof the organism’s interaction with light willalso address complexity.

AT A GLANCE

Official titleComplexity and evolution of photonicnanostructures in bio-organisms: templatesfor material sciences

CoordinatorBelgium: Facultés Universitaires Notre-Damede la Paix, Namur

Partners• United Kingdom: Natural History Museum,

London• Hungary: Research Institute for Technical

Physics and Materials Science, Budapest• Hungary: Hungarian Natural History

Museum• France: Université Pierre et Marie Curie

Further informationProf. Jean Pol VigneronLaboratoire de Physique du SolideFacultés Universitaires Notre-Dame de la PaixRue de Bruxelles 615000 NamurBelgiumFax: +32 81 724 707Email: [email protected]

Duration36 months



Project referenceContract No. 12915 (NEST)


Significant ‘technologytransfer’ from naturalbiology to syntheticmaterials science canbe achieved.

B IOPHOT



A naesthesia is a subtle and imperfectscience, with the level of anaesthesia

needing to be very carefully controlled toavoid awareness and pain while minimis-ing the risk of complications. The Bracciaproject is exploring ways in which the brain’selectrical activity, especially delta andgamma brain waves, and their interactionswith heart and breathing activity, vary withthe depth of anaesthesia. This work lookinginto the complexities of human physiologyis part of the NEST PATHFINDER initiative on‘Tackling complexity in science’.The project will use measurements onhumans and rats to explore the causal rela-tionships between oscillations in the brain,heart and respiratory system. It asks thefundamental question: ‘Which oscillationsare the drivers of others and which are beingdriven by others?’The first step is to develop a methodologyto test for causal relationships betweeninteracting complex systems. Human sub-jects will be monitored while awake andunder anaesthesia. The results will then beused to develop systems that can modelthe oscillatory behaviour of human, andmore generally mammalian, physiology.

The Braccia project is study-

ing the complex interactions

between electrical activity in

the brain, and oscillations in

heart and breathing activity

during anaesthesia. The find-

ings may reveal new ways to

monitor the depth of anaes-

thesia. The research could be

of much wider relevance,

however, because coupled

oscillatory systems are all

around us, in the natural world

and in modern technology.

Investigating anaesthesia

could therefore also help us

to understand and control

many other complex systems.

From the specific to the general

The need for a better understanding ofanaesthesia is driven by the enormousmedical and societal importance of thistechnique, without which most moderncomplex surgical procedures would beimpossible. The physiology of anaesthesiais not well understood, however, and themechanisms causing loss of consciousnessremain mysterious. Complications due toinadequate control of anaesthesia rangefrom a patient experiencing pain and someunwanted level of awareness, to rareextreme reactions that can lead to braindamage or even death. The most commonproblem is some awareness during surgery,which affects approximately 1 in every900 patients. This is particularly undesir-able in those procedures in which a patientis unable to indicate that they have becomeaware and can feel pain, as can happenwhen a muscle relaxant is used, for exampleduring Caesarean section.Greater understanding of how the body isbehaving during anaesthesia, and howconsciousness and the sensation of paincan be better monitored, would clearly beof enormous benefit in improving generalpractice in the operating theatre.

Understanding anaesthesiacould help us all

B RACCIA

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The anaesthetist's job is highly skilled.TACK LI NG COM PLE XIT Y I N SCI E NCE

AT A GLANCE

Official titleBrain, respiration and cardiac causalities in anaesthesia

CoordinatorUK: Lancaster University, Department of Physics

Partners• Czech Republic: Academy of Sciences,

Institute of Computer Sciences• Germany: University of Potsdam,

Institute of Complex Systems• Norway: University of Oslo,

Ulleval Hospital• Slovenia: University of Ljubljana,

Faculty of Medicine• Switzerland: Swiss Federal Institute

of Technology• UK: Lancaster University,

Physics Department• UK: Morecambe Bay Health Trust,

Royal Lancaster Infirmary

Further informationDr Aneta StefanovskaUniversity of Ljubljana, Faculty of Electrical EngineeringGroup of Non-linear Dynamics and SynergeticsTrzaska 25Ljubljana 1000 - SloveniaFax: +386 1 426 4630E-mail: [email protected]

Duration36 months





Levels of anaesthetic need to be carefully calculated for each patient.

Significant possibilities

The most immediate aim of the Bracciaproject is to develop the methods and theunderstanding needed to create a new andimproved kind of anaesthetic monitor. If theresults of the project are as useful as thepartners hope, the next step will be to

prepare the ground for alarge-scale study thatwould refine and testsuch a monitoring sys-tem. The Braccia projectmay be the first steptowards building a sim-ple but highly effectiveanaesthesia control sys-tem that will be found in

every operating theatre, and used to provideprecise management of anaesthesia in away that is completely impossible today.Even if that dream is not fulfilled, however,the project will greatly enhance our knowl-edge about what is going on in the bodyduring surgery, and our understanding of themany interactions within complex systemsin general.

Complex oscillating systems are foundeverywhere, however. They are involvedin many other aspects of physiology, butalso occur in industrial and engineeringsettings, within the operation of computersoftware, and in the many chemical andphysical interactions of the natural envir-onment. Insights gained by studying thecomplexities of anaes-thesia could be relevantto such varied fields assoftware development,aeronautical engineer-ing and environmentalmanagement.The project is a collab-oration between physi-cists, electrical engin-eers, information theorists, medicalscientists and clinicians. This wide multi-disciplinarity reflects the fact that, althoughdirectly focused on anaesthesia, it is explor-ing aspects of complex science that areimportant in a huge range of situations.

The Braccia projectwill greatly enhanceour knowledge aboutwhat is going on in thebody during surgery.

B RACCIA



Complexity science is revealing the func-tion and behaviour of complex networks

in the real world, including information-tech-nology networks, power grids and transportnetworks. However, the benefits of thisdeeper understanding are only slowly beingfelt by policy-makers, with those workingwith financial markets slightly ahead.The CAVES project aims to provide a linkbetween complexity science and socialpolicy. Land use is being modelled to deter-mine how it might change, for instance,in response to policy initiatives such asrevision of the EU’s common agriculturalpolicy (CAP). The project forms part of theNEST PATHFINDER initiative on ‘Tacklingcomplexity in science’. In line with this,CAVES is a highly interdisciplinary projectthat: a) helps answer important scientificquestions involving complexity, and b)encourages the transfer of knowledge andtechniques to new areas of application.

Modelling land use

The analysis of land use using complexityscience differs from traditional analyticalmethods, because no central organisingprinciple is assumed. The behaviour ofa complex network instead emergesthrough the interaction of individual quasi-

It can be hard to predict how

social policy will affect land-use

patterns and social networks.

This is because uncertainty

arises from the complexity

inherent in such systems.

Complexity science facilitates

the modelling of complex real-

world networks involving human

activity and environmental

change. These models can help

us understand how change in

the past has impacted on land

use and human populations.

Generalised models may have

wide application in formulat-

ing policy under conditions of

uncertainty.

autonomous software programs calledagents. The agents in land-use networkstypically represent stakeholders such asfarmers and industrial decision-makers.A complex network changes in response tointernal stress or external shock. A largeexternal shock, for instance, causes anepisode of volatility. In a resilient network,land use will remain largely unchanged asa consequence of this, although dramaticchanges in land use may occur in lessresilient networks.The CAVES project incorporates three casestudies, involving complex networks ofdiffering resilience. The scientific aim isto identify reasons why some complex net-works are more resilient. Models are beingconstructed retrospectively for each casestudy, using datasets of land use overtime to determine the impact of previousepisodes of stress and shock. The modelsare then run forwards in time, so that pastevidence provides the basis for exploringpossible impacts of future shocks.

Case studies

Two of the case studies are from Europe,while the third from South Africa demon-strates the relevance of the methodology

Complexity science in the service of social policy

C AVE S

TAC K L I N G CO M P L E X I T Y I N S C I E N C E

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Land-use patterns develop within a complex network of actors.

Complex models can help develop social policy which affects land use.

Aiding policy development

The CAVES project aims to demonstratehow models of complexity can help to for-mulate social policy. The two Europeancase studies, for instance, are being usedto inform discussions on CAP reform. Themodels obtained from all the case studies

are being analysed forcommon features, toproduce clusters ofgeneralised modelsthat can be applied toall complex networksinvolving land use.Both coarse and fine-grained models arebeing constructed toinvestigate the process

of scaling up. Models should be sensitiveto scale, but be amenable to forming partsof larger models. This will be importantwhen constructing global models, such asthose for land use and climate change.The identification of networks susceptibleto change will enable social policy to berefined in order to reduce the impact offuture shocks.

beyond Europe. A dataset from theGrampian region in Scotland shows thatland tenure and social structures havenot changed greatly, despite a series ofexternal shocks that include entry to theEU, changes in agricultural subsidiesand epidemics of livestock disease. Thisresilience arises through the social struc-ture of family farms,flexible land use, andother factors.A case study from theOder River Valley inPoland, on the otherhand, reveals a highrate of change in landuse since the end of theSecond World War. Thisshock arose from polit-ical events and a large-scale shift in popu-lation. Water-management systems wentinto decline and agricultural diversity wasreduced, with crops becoming more vul-nerable to flooding. The prospective part ofthis study will address how farmers in theregion might respond to fresh challengesposed by EU membership. The third casestudy, from the Limpopo Province in SouthAfrica, encompasses the large-scale land-use and demographic changes that occurredafter the fall of the apartheid regime.

AT A GLANCE

Official titleComplexity: Agents, Volatility, Evidence and Scale

CoordinatorUK: Centre for Policy Modelling

Partners• Sweden: Stockholm Environmental Institute• Germany: Universität Kassel• Poland: Politechnika Wroclawska• Austria: International Institute for Applied

Systems Analysis• UK: Macaulay Land Use Research Institute• Poland: Uniwersytet Wroclawski

Further informationProf. Scott MossCentre for Policy ModellingManchester Metropolitan UniversityAytoun BuildingAytoun StreetManchester M1 3GH - UKFax: +44 161 247 6802E-mail: [email protected]

Duration36 months





Models are run for-wards in time, so thatpast evidence pro-vides the basis forpredicting the impactof future shocks.

C AVE S



P hysicists have a complete understandingof atoms, but that does not mean that

we understand everything that atoms cando. Atoms come together to form molecules,molecules form cells, cells form people, andpeople form a society. Yet we are far fromunderstanding how societies work. Eachstep up the ladder sees a huge increase incomplexity. There have been many attemptsto model complex systems in terms of theircomponent parts but with only partialsuccess.It is commonly believed that such failingsare due to a lack of knowledge about thecomponents and how they interact. If weknew more about chemical reactions orhuman behaviour we might do better. Butaccording to the proposers of the NESTCO3 project, these approaches fail notbecause of insufficient information butbecause the models do not take properaccount of the discrete nature of the com-ponents. Conventional modelling tools usedifferential equations which treat the prop-erties of the system (such as the econ-omy) as smooth and continuous, like afluid, rather than a collection of freelyacting individuals. The proposers will usea new type of model, the ‘AB’ model, whichrecognises this difference.

Mathematical models have

long been used to simulate

complex biological, social and

economic systems. The CO3

project argues that such models

fail to take account of rare

events that can grow to change

the behaviour of the system as

a whole. The project team will

apply a new type of model to

understand the development

of private enterprise in Poland,

the spread of technological

innovation, the location of

high-tech businesses and the

development of auto-immune

disease. The results could

change the way we think about

social, health and economic

problems.

Rare events drive change

A key outcome is that random fluctuations,or ‘noise’, can, in some cases, grow tochange the collective behaviour of thewhole system. The proposers argue thatsuch rare events are, in fact, the mainmotor driving changes in collective behav-iour. It is a rather abstract concept, andthe CO3 team intend to put it to practicaluse in a number of socio-economic andbiological applications.For example, a group led by the Universityof Warsaw will create an AB model of themacro-level economic, cultural, and polit-ical mechanisms relevant for social andeconomic change. They will test it on thechanges in Poland since 1989 from a cen-tral to a market economy, where privatebusinesses have become more clusteredthan they were before, with prosperousareas alongside areas of economic decay.The University of Paris 2 will lead anotherstudy looking at how and where businessesstart up and grow. Industry has tradition-ally located in places favourable for naturalresources and transport links. But manyhad predicted that the ‘new’ industriesbased on intellectual capital, such asbiotechnology, software and media, would

The importance of rare events

CO3

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Advances in computer power make complex models easier to develop. TAC K L I N G CO M P L E X I T Y I N S C I E N C E

Complex models may help develop understanding of auto-immune diseases.

Current models are not satisfactory andthe CO3 work may help to understand theemergence of auto-immune diseases suchas diabetes and multiple sclerosis.The Bar Ilan researchers will also underpinall these studies by developing tools tohandle more realistic biological and socio-economic models which will then be usedby the other groups.

The partners expect thatthe methods developedin CO3, part of a widerNEST PATHFINDER ini-tiative on complexity inscience, will lead to abetter understandingof how the behaviourof complex systemsemerges from the cumu-lative effect of numer-ous individual agents.

In the longer term, they hope that theirfindings will be applied by many otherworkers in economics, social sciences andbiology and will have a very practicalimpact on economic planning, health andcapital investment.

not be so constrained and would bedistributed more evenly – location shouldmatter less in the connected age. This hasnot happened, and the partners will applythe AB model to understand why the newindustries have concentrated in places suchas San Francisco, San Diego, New York andLondon. They hope to discover what lessonswe can learn about supporting start-ups.

Auto-immunedisease

A third study, led by thetwo Italian partners,will examine the con-ditions under whichtechnological innov-ation can spread througha large region, and whyinnovation will tend tocluster in certain areas. This model will betested on the pharmaceutical sector.A completely different application will beled by Bar Ilan University. They will use theAB model to study the development of B lymphocytes, a type of white blood cellimportant in the body’s immune system.

AT A GLANCE

Official titleCommon complex collective phenomena instatistical mechanics, society, economics,and biology

CoordinatorItaly: Fondazione ISI

Partners• Italy: Scuola Superiore Sant’Anna• France: Université de Paris 2• Poland: University of Warsaw• Israel: Bar Ilan University• Italy: Università di Roma ‘La Sapienza’

Further informationProf. Sorin SolomonDirector, Multi-Agent SystemsFondazione ISIViale Settimio Severo, 65I-10133 TorinoFax: +39 011 660 0049E-mail: [email protected]

Duration48 months





A key outcome is thatrandom fluctuationscan, in some cases,grow to change thecollective behaviourof the whole system.

CO3



Shifting alliances of natural scientistshave tried for several decades to forge

a new science by unifying insights froman unlikely assortment of disciplines – ecology, biology, physics, geology, math-ematics, information science and more.If the COLL-PLEXITY partners are on solidground, science in-the-making – the scienceof complexity – has come of age. It is nowmature enough, they believe, to justifythe launch of a project with the potentialfor a great pragmatic pay-off.The project’s name is COLL-PLEXITY. Itsobjective is to fashion practical toolsfor industrial managers as a support toimprove their decision-making for buildingand managing inter-organisational net-works. For an increasing number ofcontemporary businesses, the ability tomanage inter-organisational networks isnothing less than vital.The importance of networking is nothingnew, of course, but it has increased withthe emergence of outsourcing, e-market-places and virtual enterprises. One of theCOLL-PLEXITY partners, the Virtuelle FabrikAG, exemplifies the trend – a network of

Companies lacking the flair

for crafting and managing

inter-organisational networks

are at a disadvantage in the

modern business environment.

Such is the complexity of these

networks that managing them

is no easy task. The Coll-plexity

consortium’s ambition is

twofold – to leverage funda-

mental insights from the new

discipline of complexity science

for managers in industry and

to advance complexity science

itself by applying it to the

social world in which network

management takes place.

72 diverse SMEs organised via three virtualfactories. By pooling the resources andcoordinating the efforts of its membercompanies, each ‘factory’ is able to manu-facture products which none of thoseSMEs could have taken on in the past.Projects involving SMEs from two or morefactories are possible, too. However, theserequire a better understanding of the oftencomplex dynamics of inter-organisationalcollaboration.

Paradigm shift

Being one of the fastest growing scientificdisciplines, complexity science has beenidentified within NEST as a field withsubstantial longer-term promise – a fieldworth strengthening in Europe. Hence, thePATHFINDER initiative on understandingcomplexity, of which COLL-PLEXITY is apart, provides a promising approach tomeet the modern challenge of intricate,interrelated processes.The disciplines from which it has emergedare all natural sciences and the complexsystems its scientists grapple with are

Handling inter-organisational complexity

!

COLL-PLE XIT Y

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To an increasing population of contemporary businesses, an ability to manage inter-organisational networks is nothing less than vital. TAC K L I N G CO M P L E X I T Y I N S C I E N C E

The project partners will fashion a generic model of complexityfor system coordination in collaborative production networks.

phenomena, it is a very tall order. Theteams have acknowledged this and orienttheir perception towards this understanding.What they expect to achieve at the endof their work is one powerful tool for thekit – a unique framework for managers

that helps to match thecomplexity of the net-works they need to buildwith the complexity ofthe problems theyintend to solve.The scientists charac-terise it as a frameworkof thought, a first steptowards eventual imple-mentation of integratedcomplexity managementsystems. As a result,these might occupy thesame capacity in future

organisations as enterprise-resource-plan-ning (ERP) and customer-relationship man-agement (CRM) systems do in present-dayorganisations. On the way to success, firstof all, the partners need to devise a classi-fication scheme for complex problems andcomplex systems in manufacturing.Beyond that, they will fashion a genericmodel of complexity for system coordinationin collaborative production networks.Schiesser AG – a COLL-PLEXITY partnerthat designs, manufactures and sellsunderwear – and the Virtuelle Fabrik AGwill be among the organisations in whichthe prototype framework will be piloted.Ultimately the project’s practical findingswill be brought together in a managers’manual presenting guidelines for setting upand coordinating collaborative networks.

physical ones. Nevertheless, with others inthe field, the COLL-PLEXITY consortiumacts on the assumption that there arefundamental regularities underlying thecomplexity of the systems that the lattershare with social systems. In respect ofthis, complexity sciencemay hold the key to anew way of tackling theproblems of industrialnetworks. Moreover,tackling such problemscould contribute tothe further advance ofcomplexity theory.By means of the avail-able tools, managementscientists usually ascribethe success or failureof inter-organisationalcollaboration effortsto stock causes. Culture or resistance tochange is one example. COLL-PLEXITY’sresearchers from institutes in Germany,The Netherlands, Israel, Switzerland andHungary hope that their theories, althoughoriginating in the natural sciences, canhelp to find causes and alternatives thatmay suggest new solutions. What theconsortium is looking for, in its own words,is ‘a true paradigm shift’.

Generic model of complexity

Creating a toolkit for ordinary managersfrom the methods and theories of anunfamiliar science is no easy task. Whenthe environments in which their companiesoperate are social by nature and thescience in question is a science of physical

AT A GLANCE

Official titleCollaborative Complexity,Collaborations as Complex Systems

CoordinatorGermany: Rheinisch-Westfälische TechnischeHochschule Aachen (RWTH) – Laboratory forMachine Tools and Production Engineering(WZL)

Partners• The Netherlands: TU Delft – Faculty of

Technology, Policy and Management (TPM)• Israel: Global Research and Financing• Switzerland: Universität St. Gallen,

ITEM-HSG• Hungary: The Computer and Automation

Research Institute - Hungarian Academy of Sciences (SZTAKI)

• Germany: Schiesser AG• Switzerland: Virtuelle Fabrik AG

Further informationProf. Günther SchuhLaboratory for Machine Tools and ProductionEngineeringChair for Production EngineeringFaculty of Mechanical EngineeringSteinbachstraße 53B52074 Aachen, GermanyFax: +49 241 80 22293E-mail: [email protected]

Duration36 months





Improved understand-ing of the manage-ment of complexitywill accrue from a thor-ough understanding,description and mod-elling of complexityin inter-organisationalenterprise networks.

COLL-PLE XIT Y



T he prime function of financial markets isto bear risk, enabling the transfer of

resources from suppliers of liquidity toentrepreneurs and risk-takers. In order to dothat efficiently, they must ensure a properreturn on capital, coupled with market sta-bility so that long-term planning may pro-ceed with confidence and resources canbe allocated efficiently. But the operation ofmarkets is often accompanied by periodsof instability and excessive volatility, includ-ing speculative ‘bubbles’ and crashes.Complex Markets, part of the NESTPATHFINDER initiative on ‘tackling com-plexity in science’, aims to explore an alter-native to the classical theory of rationalbehaviour of a single agent. The alterna-tive proposes a large number of hetero-geneous agents within markets – each ofwhich can employ rational behaviour –but the interaction between these agentsallows collective effects to arise. In thisway, the financial market behaves as acomplex system. Within such a heteroge-neous system, traders can either basetheir investment decisions on the marketfundamentals (dividends, earnings, inter-est rates) or go by patterns and trends inrecent prices. Irregular switching betweenthese two strategies can occur, resultingin irregular price fluctuations.

Research in the area of het-

erogeneous agents and inter-

action in the modelling of

financial markets has made

rapid progress since the 1990s.

Advances in theoretical tools

and computational capacity to

analyse and simulate large

systems have given new insight

into market behaviour. The

Complex Markets project brings

together an interdisciplinary

team to explore these develop-

ments in depth. A more com-

prehensive understanding of

market behaviour will enable

more effective management

and produce greater stability.

Unravelling the strands

Complex Markets brings together leadingresearchers in numerical simulation, experi-mental economics, mathematical analysis,finance, econometrics and psychology. Itwill build in high-level contact with thefinancial industry and the Bundesbank,the Bank of England and the EuropeanCentral Bank, and specialist advisers inthe US.The team plans to collect and analyse dataon behaviour in specific markets, includingmarkets for wholesale fish, fruit and vege-tables and internet auctions. ComplexMarkets will also study the structure offoreign-exchange markets and stock mar-kets, evaluating the extent and effects ofbehaviourial networks. The prices in mar-kets where traders interact and trade withina small group of other traders, rather thantake the apparently best deals on theirscreens, appear to be much more volatilethan in markets with an electronicallyorganised order book. These studies shouldform the basis for understanding theprocesses that lead to bubbles and crashes.The basic data will also enable the projectteam to derive the general principles ofthe evolutionary approach to the behaviour

Financial trading is a complex business

COM PLE X MARKETS

Access to information is critical to well-functioning financial markets.TAC K L I N G CO M P L E X I T Y I N S C I E N C E

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The project will develop greater understanding of market behaviour.

ability of the unknown elements of theirenvironment for decision-making. Uncer-tainty acknowledges that in many casesthey cannot rely on this probability, becauseof the possibility of ‘one-off’ events of

which they have noexperience, and there-fore no basis for a risk-based analysis basedon a known probability.Complex Markets willuse its varied expertiseto take uncertainty intoaccount in studies ofhow individuals react ina complex environmentwhich is only partiallyunderstood, and there-fore its effect on indi-

vidual financial decision-making and onthe collective market outcome.Stock markets, exchange, commodity andderivative markets all share the same prop-erties, so the Complex Markets projectshould reveal whether these human multi-agent systems work according to commonprinciples in the same way as physical andbiological systems.

of financial markets, ranging from simplemodels of a rational agent forecasting onthe basis of unknown parameters, to com-plex models with interacting traders withco-evolving strategies. Estimation of suchcomplex systems isstill very new, but evi-dence suggests thatsuch an evolutionarysystem could accountfor the volatility wesee in markets. It willalso show whetherinternational trade andlong-term capital move-ments are distorted byshort-term speculation– an important outcomefor policy-makers

Risk and uncertainty

Complex Markets will use psychologicaland economic insights to develop a deeperunderstanding of decision-making in com-plex environments exploiting the conceptsof risk and uncertainty. Risk refers to indi-viduals being able to evaluate the prob-

AT A GLANCE

Official titleFinancial markets and complexity:uncertainty, heterogeneous micro agentsand aggregate outcomes

CoordinatorUK: University of Warwick

Partners• France: Université Aix-Marseille III• Germany: University of Kiel• Italy: Abdus Salam International Centre

for Theoretical Physics• Italy: University of Cagliari• The Netherlands: University of Amsterdam

Further informationProf. Mark SalmonWarwick Business School, University of WarwickCoventry CV4 7AL - UKFax: +44 24 7652 3779E-mail: [email protected]

Duration36 months





The project will usemathematical, psycho-logical and economicinsights to developan understanding ofthe observed charac-teristics of financialmarkets.

COM PLE X MARKETS



W hy did stem-cell research suddenlybecome such an issue in the 2004

US presidential election? What is fuellingthe simmering controversy about genetic-ally modified foods? How are the researchchoices of scientists influenced by whatappears to be fashionable at the time? Inshort, why do scientific research topics likethese suddenly erupt from the labs andsaturate the media? The partners in the CREEN (Critical eventsin evolving networks) project call thesephenomena ‘scientific avalanches’. Just asan avalanche of snow can be forecast bycareful modelling and study of environ-mental conditions, it may one day be pos-sible to predict under what circumstancesscientific avalanches will happen. Andcould we even trigger an avalanche in aconstructive and desirable direction?Such questions can only be answered bya truly interdisciplinary effort from manybranches of the natural and social sci-ences. This project, part of a wider NESTPATHFINDER initiative on complexity inscience, will draw on many strands ofresearch on how information spreads withinsocial networks. Scientists, like journal-ists, are individuals, but the collectivebehaviour of science or the media can beunpredictable, related in a complex wayto the actions of individuals within them.

Research breakthroughs, con-

troversies and fashions in

science can emerge unex-

pectedly, sometimes with

unwelcome political and eco-

nomic effects. What triggers

these so-called ‘scientific ava-

lanches’? An interdisciplinary

team from five countries will

apply insights from physics,

mathematics and the social

sciences to the complex social

networks of science and the

media. Why do such critical

events occur and can their

probability be estimated? The

results will be of interest not

only to scientists and jour-

nalists but also to science

policy-makers.

Linking social science and physics

The proposers, from five countries, aretheoretical and statistical physicists, spe-cialists in socio-physics, computer scientists,mathematicians, information and com-munication scientists and sociologists.Prof. Janusz Holyst, from the Warsaw Uni-versity of Technology, is coordinating theproject. His group will apply the principlesof statistical physics to social networks.For example, thermodynamics predictshow liquids boil or freeze – can we learnsomething about sudden social changesfrom such analogies? Another approachwill look at what happens when a networkof scientists interacts with a network ofjournalists, which in turn interacts with anetwork of newspaper readers or TV viewers.The second topic, led by the University ofLiège, will deal with how scientists andother people organise themselves intoformal and informal networks and howindividual decisions can affect collectivebehaviour. Researchers will look at howideas spread through the scientific com-munity, leading to an avalanche when top-ics suddenly become fashionable.The project will create natural links betweenphysics and social-science methodology.One of these links points to a group led bythe Royal Netherlands Academy that will

Scientific avalanches

CR E E N

When science makes headlines scientists themselves may be unprepared for the controversy.TAC K L I N G CO M P L E X I T Y I N S C I E N C E

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The different interactions between science and society make up a complex relationship.

it to the results from the other groups inCREEN.The proposers freely admit that what theyare trying to achieve is well ahead of thestate of the art but the risk of failure isoffset, they say, by the promise of majoradvances leading to social and economicbenefits. When the project is complete inthree years time, the proposers hope notonly to have gained a deeper understand-ing of how science and society interact, butalso to be able to help policy-makers antici-

pate where avalanchesare likely to happen andto deal with them effect-ively. They even specu-late that their findingsmay have applicationsin other multidiscip-linary studies such asriver flooding, protec-tion of species in foodwebs and trade-network

crashes. They will disseminate their find-ings to policy-makers, journalists andother experts through meetings, brochuresand a website.

look at the influence of ‘media hype’, andseek ways to model and measure ava-lanches, applying their methods to suchreal-life controversies as BSE, foot-and-mouth disease, genetically modified foodsand stem-cell research.

Influence of ‘bloggers’

Meanwhile, the University of Wolverhamptonwill lead a study into how the world-wideweb is being used as medium for scien-tific debate. They willanalyse the content ofon-line newspapers,personal web pagesand especially ‘blogs’,to track how the webhas influenced recentavalanches and also tospot new avalanchesas they take place.Finally, a group led bythe University of Karlsruhe, will developmethods of visualising complex informa-tion, based on the results of a previousEU-funded project (COSIN),and applying

AT A GLANCE

Official titleCritical events in evolving networks

CoordinatorPoland: Faculty of Physics and the Centre ofExcellence for Complex Systems Research,Warsaw University of Technology

Partners• Belgium: SUPRATECS group,

University of Liège• Netherlands: Netherlands Institute

for Scientific Information Services, Royal Netherlands Academy of Arts and Sciences

• UK: Research Institute for AdvancedTechnologies and School of Computingand Information Technology, University of Wolverhampton

• Germany: Faculty of Informatics, University of Karlsruhe

Further informationProf. Janusz HolystFaculty of Physics and Centre of Excellencefor Complex Systems ResearchWarsaw University of TechnologyKoszykowa 75PL-00-662 WarsawFax: +48 22 628 2171E-mail: [email protected]

Duration36 months





Scientists, like journal-ists, are individuals,but the collectivebehaviour of scienceor the media can beunpredictable...

CR E E N



T he Dysonet project is looking at a rangeof complex social networks. Its inter-

disciplinary team aims to develop techniquesfor specific problems, like the dynamics ofcrowd behaviour, which can then be testedin other more general systems. There aremany unanswered questions about the struc-ture of networks and about flows throughthem (e.g. of information). Ultimately themethods will be made available to researchersin all fields of study through the internet.Dysonet is part of the NEST PATHFINDERinitiative on ‘Tackling complexity in science’.

Real data analysis

Dysonet participants will first (with per-mission) collect real-world data from socialnetworks in Sweden, covering networks ofpeople who share the same household, workat the same workplace, live in the samebuilding, attend the same hospitals, or arepart of networks of sexual partners. It willalso collect financial data for study of thedynamics of different types of portfoliostraded in financial markets.Most of the individuals in social networks(nodes) have a small number of connec-tions, but a few have a very large number.Network models will be developed by

In recent years it has become

clear that common principles

underlie the behaviour of

many systems in the real

world, which are composed of

units connected into complex

networks. Such networks occur

in nature, physics and in many

aspects of human social behav-

iour. DYSONET is applying

mathematical principles to

understand the dynamics of

social networks. Study of real

examples will improve under-

standing of how to optimise

real-world networks, for ex-

ample in limiting the spread

of epidemics.

Dysonet to allow study of robustness(the number of nodes which must beremoved before connectivity of a networkis destroyed) and the capability for net-work flow (the features of the optimalflow path, using the least time, energy orcost). To do this, the team will make use oflarge-scale computer simulations and gridcomputing, and develop new analytical,numerical and simulation techniques. Theinformation gained will be used to identifydesigns of network models showing thebest robustness and flow. The networkanalysis will then be applied to the real-world data, and should make largeadvances in understanding complex humansystems.

Practical applications

Dysonet addresses five areas of collectivehuman behaviour. The first will look at thespread of information and rumours acrossnetworks which, enhanced by mobile com-munications, can escalate out of control.Knowledge of this phenomenon will preventfurther rumours like the one in Hungary inJune 2003, which caused nationwide panicabout a nuclear explosion. Understandingthe relay of information through a crowd in

Understanding the dynamicsof human behaviour

DYSON ET

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Human behaviour depends on a range of networks with different networks cominginto play in given situations.TAC K L I N G CO M P L E X I T Y I N S C I E N C E

Crowd behaviour may contribute to deteriorating situations such as traffic jams.

als are immunised randomly, but if themost-connected individuals are targeted,immunisation is much more effective. How-ever these key individuals are very hard toidentify. Dysonet studies will improve theefficiency of such targeting.In finance, collective behaviour is shownby adaptation to market changes, andin extreme cases to response to unex-

pected events, leadingto changes in stockprices and even publichysteria. Such responsesdepend on the structuresunderlying informationflow. Better understand-ing of the behaviour ofthis information flowwould inform marketregulatory policies. Tobe able to do so, Dysonet

is investigating the structure of portfoliosfrom leading and emerging financial mar-kets. Later, the findings and methods willbe applied to a commodity market, to exam-ine common features of the two systems,so that the methods can then be applied toother types of networks.

panic will help develop more efficient evacu-ation methods, for example from footballcrowds, earthquakes or terrorist attacks.The behaviour of networks can contributeto organised search strategies, e.g. for miss-ing persons. In a random search, a newdirection and distance are selected by thesearcher every time the target is not found;better understanding of this behaviourwill help to designmore effective collec-tive search methods.Traffic flow is an exampleof crowd behaviourwhere enhancing flowis important. If a largenumber of drivers areheading in the samedirection, their choiceof route will be influ-enced by the same infor-mation, from their observations and trafficreports. Collective behaviour emerges,making the bottlenecks worse. This studywill contribute to more effective distribu-tion such as of food and medical aid.An area where the aim is to minimise flow,is that of epidemics. The epidemic spreadof disease is almost inevitable if individu-

AT A GLANCE

Official titleHuman behaviour through dynamics ofcomplex social networks: an interdisciplinaryapproach

CoordinatorGreece: Aristotle University of Thessaloniki

Partners• Germany: Justus-Liebig-Universitaet

Giessen • Israel: Bar-Ilan University• Italy: Instituto Nazionale

per la Fisica della Materia • Portugal: Universidade de Aveiro• Sweden: Stockholm University• USA: Boston University

Further informationProf. Panos ArgyrakisUniversity of Thessaloniki GR-54124 ThessalonikiFax: +30 2310 998 042E-mail: [email protected]

Duration36 months





The analysis will makemajor advances inunderstanding com-plex human networksinvolving spread, forexample of informa-tion or disease.

DYSON ET



C omplexity and self-organisation arecritical to many biological systems, yet

many questions about how complexityemerges from simpler starting states remainunanswered. Current computer simulationsof complex systems in biology take manyhours to achieve a rather poor copy of whatNature manages perfectly in a split second.The EMBIO project, part of the NEST-PATHFINDER initiative on ‘Tackling com-plexity in science’, aims to provide newtools and approaches to help answer someof these questions. By focusing on oneof the major challenges in modern biology– protein folding – they hope to identify thefundamental principles governing the emer-gence of complexity in self-organisingbiomolecular systems. The interdisciplinary research consortium,comprising eight European laboratorieswith expertise in mathematics, statisticalphysics, chemistry, information theory,biology and computing, will develop highlyinnovative mathematical and computa-tional approaches to characterise thedynamics of self-organisation and applythese to protein structure. Because of its focus on protein folding,EMBIO will have a particular impact inmolecular and structural biology, but its

Complexity has a key role to

play in biology yet is still

poorly understood. A European

project, EMBIO, aims to pro-

vide the research community

with new methodologies based

on innovative mathematics and

software to help make sense of

the dynamics of self-organi-

sation. By focusing on the

emergence of complexity in

protein folding, the project

team will be addressing one

of the major problems in

modern biology, and their

results will have important

implications for drug discovery.

innovative approach to analysing com-plexity will be relevant to many other sys-tems that give rise to self-organisation.

From chaos to calm

Protein folding is a striking example ofemergent complex behaviour and, beingwell defined, it is an ideal system in whichto study complexity. Most proteins spontan-eously and reproducibly fold from an arbi-trary chain of amino acids to a specific 3Dstructure adapted to their biological function.But although data exists on the chemicalcompositions and structures of thousandsof proteins, it is still not possible to predictaccurately or to explain how and why thistransition to a folded structure takes place,partly because it is a non-linear, dynamicprocess influenced by many factors.As the protein’s final 3D structure is consid-ered the most thermodynamically stableone, scientists currently use a ‘folding fun-nel’ model to explain the dynamics of thetransition. Initially, the chaotic motions ofthe atoms have high levels of free energyand occupy large areas of potential foldingspace. As the protein molecule folds and itsfree energy decreases, the available spaceis reduced to the point where the molecule

Emerging complexity in protein folding

E M B IO

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TAC K L I N G CO M P L E X I T Y I N S C I E N C EThe project will focus on protein folding.

© Embio

Improved understanding of protein folding is vital to the pharmaceutical industry.

understanding of how proteins fold islikely to bring strategic benefits and muchneeded innovation to drug discovery. Mostnew drugs target specific proteins in thebody. In addition, misfolded proteins aredirectly implicated in a number of debili-tating conditions such as Alzheimer’s andCreutzfeldt-Jakob disease.

The consortium alsoexpects its work oncomplexity estimationto impact on areas ofstudy involving compli-cated chaotic dynamics.Examples of these areheart rhythms, where abetter understandingof their chaotic naturecould lead to new diag-

nostic tools for heart disease, and electro-magnetic signals, which are generated inphotonic devices used for optical commu-nication. More generally, if EMBIO succeeds in iden-tifying the generic features which charac-terise dynamic complexity, their results willbe widely applicable by the scientific com-munity for the study of complexity in areasas diverse as social science or forest fires.

is ‘forced’ into its final structure, corres-ponding to its minimum energy.Whilst this model is now generally accepted,it does not explain many aspects of proteinfolding, notably the speed at which it takesplace. The EMBIO consortium will developa new computational approach which willprovide a more accurate description ofthe dynamics involved,taking into accounttemporal, topological,statistical and dynamicproperties. Powerfulstate-of-the-art com-puting facilities avail-able within the con-sortium will enablesophisticated ‘all atom’simulations of foldingand the generation of new data on whichto base novel methods and algorithms.

An alternative view

The new methodologies developed byEMBIO, underpinned by innovative math-ematical approaches and applicationssoftware, will open the door to an alter-native view on protein folding. A greater

AT A GLANCE

Official titleEmergent organisation in complexbiomolecular systems

CoordinatorUK: University of Cambridge

Partners• Austria: University of Vienna• Germany: Friedrich-Schiller-University Jena• Germany: University of Heidelberg• Germany: University of Leipzig• Italy: University of Florence• Sweden: Chalmers University of Technology• The Netherlands: University of Groningen

Further informationProf. Robert Charles GlenUniversity of CambridgeUnilever Centre for Molecular Informatics,Department of ChemistryLensfield RoadCambridge CB2 1EW, UK Fax: +44 1223 763076E-mail: [email protected]

Duration42 months



Project referenceContract N° 12835 (NEST)


Advances in under-standing protein fold-ing will bring muchneeded innovation tothe drug discoverybusiness.

E M B IO



The earthquake and tsunami that ravagedmany communities around the Indian

Ocean in December 2004 were typical ofwhat are called extreme events. They cameas a complete surprise, even though thearea was well known as an earthquake zoneand the underlying geophysical mechan-isms were well understood. Other extremeevents include floods, storms, droughtsand landslides. Not all such events havenatural causes: stock-market crashes,bridge collapses, crime waves and terroristattacks are of human origin but share manyof the same characteristics. A third groupof events – possible catastrophic effects ofclimate change on the economy – have bothnatural and human origins.What they have in common is that they arenot well described by conventional stat-istical methods. Mathematical models ofgeophysical, climatic or socio-economicsystems may have some success in describ-ing their normal state or gradual changesbut are not able to predict sudden, extremeevents. And, what is more, these events doseem to be more common than conven-tional statistical analyses would suggest.

Earthquakes, floods, storms,

riots and stock-market crashes

have one thing in common:

they cannot be successfully

described by conventional

statistical methods. Such

‘extreme events’ are the focus

of E2-C2, a 17-partner NEST

project trying to understand,

and perhaps predict, some of

these unexpected and dam-

aging occurrences. Among

other things, the project will

look at the social and eco-

nomic effects of impending

climate change and even

attempt to forecast crime

waves in major urban centres.

Interconnected hazards

The E2-C2 project, part of a wider NESTPATHFINDER initiative on complexity inscience, will take a new look at both naturaland socio-economic hazards and the con-nections between them. The 17 partnersfrom nine countries will attempt to predictextreme events and also examine theirconsequences.The first task will be to improve the stat-istical theories used to model extremeevents. Conventional statistical methodsare very poor at describing events thathappen infrequently, so a team will devisenew methods of analysis and prediction,and test them against a variety of histor-ical records.The second line of research will look atextreme climatic events in Europe thatarise from the way in which greenhouse-gas emissions and volcanic eruptionsinteract with natural climate variability.Partners will use atmospheric models tosimulate the effects of global warming onthe North Atlantic and Western Europe,and historical and geological records fromthe Campania region of Italy to investigateconnections between volcanic eruptionsand climatic extremes.

Making sense of extreme events

E2-C2

Extreme events can’t be predicted with traditional statistical methods.TAC K L I N G CO M P L E X I T Y I N S C I E N C E

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Better understanding of extreme events will help prepare communities better to deal with them.

hydrological extremes and landslides. Theywill attempt to simulate such events anddevelop methods for forecasting them.The Carpathian Mountains in Romania areknown for their major earthquakes, andanother group will take on the goal of dev-eloping an earthquake prediction system

for the Vrancea region,one of the world’s bestnatural laboratories forstudying earthquakesand landslides.Finally, in perhaps themost ambitious activityin the E2-C2 project, agroup will attempt tocreate a ‘socio-economicbarometer’ to monitorconditions in major urbancentres and provide day-by-day forecasts forimpending crises such

as crime waves, outbreaks of mass vio-lence and surges in terrorist activity.All these extreme events share a commoncharacteristic: the bigger the event the lesslikely it is to happen, but the greater thesocial and economic costs if it does. It is toosoon to say how successful the E2-C2 pro-ject will be, but any progress towards under-standing and anticipating the unexpectedis bound to pay off in the long run.

Can a climatic extreme cause a reversal inthe economic cycle? This is one of severalquestions on the relationship betweenclimate and the economy that will beaddressed by the third research group.Conventional long-term economic modelsare unable to cope with short-lived eventssuch as the winterstorms of 1999 or eventhe summer heat-waveof 2003. Therefore thisgroup will aim at devel-oping novel, fully inte-grated, dynamic modelsof the coupled climate-economy system.

Emergencyplanning

One reason why weneed to understandextreme events is so that we can preparefor them in the design of buildings, controlof land use and emergency planning. Ineach case, we need to know how oftenand how big any events are likely to be.Another task will be to look for evidencethat extreme events are not random, butthat one event may increase the likelihoodof another. The team will look at recordsof strong winds, rogue waves, forest fires,

All these extremeevents share a com-mon characteristic:the bigger the eventthe less likely it isto happen, but thegreater the social andeconomic costs if itdoes.

E2-C2



AT A GLANCE

Official titleExtreme events: Causes and consequences

CoordinatorFrance: Ecole Normale Supérieure (ENS)

Partners• France: Laboratoire des Sciences du Climat et

de l’Environnement, joint institute of CentreNational de la Recherche Scientifique (CNRS)and Comissariat à l’Energie Atomique (CEA)

• France: Société de Mathématiques Appliquéeset de Sciences Humaines

• France: Centre International de Recherches sur l’Environnement et le Développement

• Germany: Meteorological Institute, Universität Hamburg

• Germany: Interdisciplinary Centre for Dynamicsof Complex Systems, Universität Potsdam

• UK: King’s College London• Italy: Physics Department,

Università degli Studi di Roma “La Sapienza”• Belgium: Physics Department,

Université de Liège• Belgium: Institut Royal Météorologique

de Belgique• Russia: International Institute of Earthquake

Prediction Theory and MathematicalGeophysics, Russian Academy of Sciences

• Italy: Istituto di Ricerca per la Protezione Idrogeologica, Consiglio Nazionale delle Ricerche (CNR)

• Italy: Dipartimento di Fisica Generale, Università degli Studi di Torino

• Romania: Institute of Geodynamics of the Romanian Academy

• USA: Institute of Geophysics & PlanetaryPhysics, University of California at Los Angeles

• France: Institut de Physique du Globe de Paris• Luxembourg: Centre d’Etudes de Populations,

de Pauvreté et de Politiques Socio-Economiques

Further informationProf. Michael GhilDépartement Terre-Atmosphère-Océan (TAO)Ecole Normale Supérieure24 rue Lhomond – F-75231 ParisFax: +33 1 4336 8392E-mail: [email protected]

Duration36 months





F ungal growth, supermarket supply chainsand the clustering of biotech companies

may sound like disparate areas of study.However, an understanding of each can beobtained by analysing them as networks.Biological networks share common featureswith other complex networks, in terms oftheir overall structure and dynamics. Oncethe general principles governing differentkinds of complex networks are understood,steps can be taken to improve real-worldnetworks.The MMCOMNET project has set out tomeasure and model complex networksfrom different domains, with the goal ofunderstanding their structure, function andbehaviour. The multidisciplinary consor-tium forms part of the NEST PATHFINDERinitiative on ‘Tackling complexity in science’.This aims to encourage the study of com-plex systems and the transfer of know-ledge between different disciplines.

Measuring networks

Networks can be studied using macro-scopic or top-down approaches, or usingbottom-up approaches utilising recentfindings from the science of complexity.The MMCOMNET project seeks to inte-grate these approaches, in order to developstatistical techniques and software tools

Recent advances in the science

of complexity facilitate the

measurement of networks.

Certain classes of complex net-

works seem to share common

structural characteristics, and

more importantly may also

exhibit analogous functional

properties. The quantification

and modelling of networks

enables general rules to be

formulated concerning their

dynamic and functional behav-

iour. The MMCOMNET pro-

ject uses a multidisciplinary

approach to measure and

model biological, socio-

economic and business

datasets, with the aim of

predicting, managing and

designing behaviour in a wide

range of real-world networks.

to analyse complex networks. Methodsfor measuring local (individual nodes) andglobal behaviour are also being assessedusing existing datasets.Data from three domains, representingbiological, socio-economic and innovationnetworks, are being measured. The specificexamples were chosen for ease of datacollection, and their promise as genericmodels. The biological system is a fungalnetwork: one of the simplest living sys-tems to show adaptive behaviour. The mainsocio-economic system is a supply-chainnetwork, involving the flow of information,money and goods from manufacturing,distribution and retail organisations acrossEurope. Datasets on public transport inPoland and traffic networks in Germanyare also being analysed. The innovationsystem involves datasets showing theclustering of high-tech businesses, asoccurs in California’s Silicon Valley. Inparticular, a comprehensive dataset of thepopulation and businesses in Stockholmover a 10-year period is being used.

Bottom-up analysis

The three types of system consist of mul-tiple interconnected layers, comprisingautonomous agents which allocate resourceswithin the network. Agents distribute

Network news

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TACK LI NG CO M PLE XIT Y I N SCI E NCE Fungal growths show common features with commercial networks.

Traffic-network modelling provides insight into understanding complex networks.

Manipulating networks

Model networks can be used to identifyways of altering the structure or behav-iour of real-world networks to enhancedesirable properties, such as robustness,persistence, flexibility, responsivenessand efficiency. Adjustments in the localdecision-making behaviour of agents, for

example, may be effec-tive in achieving desir-able global stability.The overall aim of theproject is to generatemodelling approachesand formulate universalprinciples to aid in themanagement of complexnetworks in real-worldsituations. The desirableproperties observed in

model networks can potentially be trans-ferred, for example, to networks involvingcomputers, information, business andenterprise, power grids, and railway andother transport systems. The potentiallong-term benefits from this project aretherefore great, and could improve the qual-ity of life of almost everybody in the EU.

resources on the basis of incomplete ornoisy information. They typically act with-out a central control mechanism. The char-acteristic behaviour of networks emergesthrough the interactions of agents. Agentsmay be cells, people, or companies, in thecase of biological, socio-economic andbusiness networks, respectively.The project exploits advances in complexityscience to elucidatethe individual and col-lective behaviour ofagents. The partici-pants are developingmodels which simulatethe different combina-tions of agents andnetwork dynamics thatcan account for desir-able behaviour. Criteriafor choosing betweenalternative combinations provide insightsinto how agents and networks adapt, andthe trade-offs that occur between differ-ent network functions. In the case of thesupply-chain model, for example, the con-ditions that enable networks to retaintheir integrity in the face of local disrup-tions are being investigated.

AT A GLANCE

Official titleMeasuring and Modelling Complex Networksacross Domains

CoordinatorUK: University of Oxford

Partners• Germany: Technische Universität Dresden• Poland: Politechnika Warszawska• France: INSEAD Business School• Switzerland: Swiss Federal Institute of

Technology Zurich• Sweden: Stockholm University

Further informationDr Felix Reed-TsochasSaid Business SchoolUniversity of OxfordOxford OX1 1HP - UKFax: +44 1865 288805E-mail: [email protected]

Duration36 months





Once the generalprinciples governingcomplex networks areunderstood, steps canbe taken to improvereal-world networks.

MMCOM N ET



S tarling (Sturnus vulgaris) flocks containmany autonomous individuals. How-

ever, the behaviour of the flock cannot simplybe explained by deducing the behaviour ofindividuals. The system is said to be complex,because its behaviour emerges through theinteraction of individuals or agents that arefollowing relatively simple rules.

Bird behaviour

The findings of this project will be ofimmense interest to those working inornithology, animal behaviour and ethol-ogy. Once airborne, consistent patternsquickly appear in a group, or murmation, ofstarlings. Innovative data recording and3-D modelling techniques are being deployedto study the movements of individuals andthe shape of the overall flock. A key technicalchallenge has been to identify individualbirds over time, in images recorded fromthree directions. There have been manyprevious studies on flocking behaviour, butnone with the precise and accurate datacollection or the 3-D modelling capabilitiesof this project.One of the forces driving the evolution ofgrouping in animals is predation. Flockingbehaviour in this study will be recorded

The study of biological systems

can provide insights into the

behaviour of complex socio-

economic systems. Flocking in

birds is a complex system that

is amenable to study. Advances

in techniques for visualising

and analysing the movement

of flying birds in 3-D are leading

to a better understanding of

flocking and other animal group

behaviours. The techniques

developed can be applied to

more complex systems that

are harder to observe directly,

including the behaviour that

drives financial markets.

with and without the presence of a ‘predator’to observe changes in collective behaviour.In addition to field recordings, experimentsare being conducted in aviaries. Bird behav-iour changes seasonally, and this is beingcorrelated with an analysis of hormone levelsand social bonding. This will be a steptowards understanding the endocrinecontrol of flocking. The project will providegeneral insights into migration, navigationand animal-group movement.

Modelling collective behaviour

The models start with the idea that individ-ual agents are responsive to the behaviourof others nearest them. Flocks of starlingsexhibit anti-predator responses, for instance,which take the form of ‘terror waves’ that arepropagated through the flock. The behaviourof individuals at the sides and front of theflock are of particular interest in initiatingchanges in collective behaviour.The statistical methods, software tools andvisualisation techniques developed to studystarlings are all easily transferable to otherdomains of study. A range of measure-ments, for instance, to quantify the popu-lation level or density of agents necessaryfor emergent behaviour, can be applied

How starling flocks can help prevent financial panic

STARF L AG

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A flock of starlings… TAC K L I N G CO M P L E X I T Y I N S C I E N C E

…or a floor of traders?

crash) or favourably (with rapid adaptationto a changing environment).One area where general models of com-plex systems can be applied is to the

problem encountered infinancial systems whencollective frenzy over-rides the rationalityneeded for market effi-ciency. In strictly model-ling terms, collectivefrenzy shares commonfeatures with the ‘terrorwaves’ observed in star-ling flocks. The modelscould suggest waysfor regulators to act

to stabilise markets. A range of otherinsights into human herding and collectivedecision-making are likely to arise fromadvances made in this project.

generally to complex systems. In particu-lar, the project will use collective animal-movement models to gain insights intohuman behaviour in the social sciencesand economics.

Money matters

At the end of the Star-flag project, a simula-tion package will bedelivered, for applica-tion to complex sys-tems such as financialmarkets. In essence, itwill predict the interac-tion between individualopinion and collective group behaviour. Incases where individual opinion causes arapid change in collective opinion, a systemcan either change detrimentally (with a

AT A GLANCE

Official titleStarlings in flight: understanding patterns of animal group movements

CoordinatorItaly: Istituto Nazionale per la Fisica della Materia

Partners• France: Commissariat a l’Energie

Atomique, Centre d'Etudes de Saclay• Germany: Max Planck Society• Hungary: Eötvös Loránd Science

University• Italy: Istituto Superiore di Sanità• Italy: Scuola Normale Superiore• The Netherlands: Centre of Ecological and

Evolutionary Studies of RijksuniversiteitGroningen

Further informationProf. Giorgio ParisiIstituto Nazionale per la Fisica della Materia(INFN)Università di Roma La SapienzaP. Aldo Moro 2I-00185 RomaFax: +39 06 446 3158E-mail: [email protected]

Duration36 months





The project will usecollective animalmovement models togain insights intohuman behaviour inthe social sciencesand economics.

STARF L AG



It is now well established that manyfeatures of the physical, biological, and

sociological world – like molecular struc-tures, neural transmission, crowd behav-iour – are organised in systems or networks.They exist on an infinite range of levels ofsize and complexity, but all are characterisedby the ability of the network to respondcollectively to external conditions or stimuli.Many different theories have been de-veloped in parallel to analyse and modelthese systems. The current stage of scientificunderstanding presents an unrivalled oppor-tunity to develop a more unified networktheory. This is the intention of Uninet, partof the NEST PATHFINDER initiative on ‘Tack-ling complexity in science’.The consortium includes leading researchworkers in five widely differing areas:genetics, metabolism, neurobiology, ecol-ogy and economics. Within each area, theleading group will first review the existingnetwork theories which attempt to describeit. Later, each group will study, model andsimulate up to three topics of particularimpact in that area, which should alsoyield methodologies useful in some of theother subjects. Mathematical analysis ofthe network theories will be provided bythe coordinating group. Finally the project

The growth of studies of com-

plex systems has revealed

that they exist on many scales,

from the molecular to the

global, and in many different

fields of science. Uninet is

attempting to unify the variety

of network theories which have

been proposed for these var-

ied systems. Applying math-

ematical techniques to analyse

complex networks in five very

different areas, Uninet should

enable re-interpretation of

the original theories in new

applications, so that major

improvements of insight are

expected.

will examine their potential applications intechnology and industry.

A world of networks

Understanding complex networks is ascience in its infancy, as computers haveonly recently made it possible to analysethe huge amounts of data needed. Forexample, the explosion of data generatedby genomics still leaves a very long way togo before its implications are unravelled.Similarly, analysis of the behaviour ofindividual animal species, or of functionalgroups like a food web reveals only a frac-tion of the complexity of the whole ecosys-tem and its dynamics. And we all live in avariety of social networks, with differentlevels and scales of interaction from indi-viduals to nations, involving many differentflows, of traffic, of people or of information,for example.Uninet’s five areas for study will be linkedby annual workshops throughout theproject. These will give participants theopportunity to explore aspects of networkmodelling, including data, dynamics androbustness. It will also bring out commonaspects so that models can be reduced incomplexity to the simplest mathematical

A unified approach tointerpret complex networks

U N I N ET

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Complex networks exist at all scales of nature.© Roche 2005TACK L I N G CO M P L E X I T Y I N S C I E N C E

Biological systems are robust enough to maintain themselves under outside pressure.

genetic and metabolic networks shouldcontribute to optimising drug effects.Studies of enzyme behaviour may offerenhanced yield in biotechnological pro-duction. In the area of biological diver-sity, principles derived from ecosystemanalysis will enable Uninet to advise on

conservation strategies,especially for problemslinked with loss of diver-sity through disturbanceof food webs. Neural sys-tem research in Uninetwill advance under-standing of impulsetransmission and brainfunction. And in therather different but com-parable area of eco-nomic networks, Uninet

research on world markets and majorauctions (like privatisation) will providevaluable guidance for policy-makersconcerned with improving the efficiencyof market structures. By completion,Uninet will have created new and improvedalgorithms for solving network-relatedproblems, with wide-ranging potentialapplications.

abstraction. The work packages to beundertaken in each of the individual areaswill examine the methods that have beenused to derive networks and their dynam-ics, which include clustering algorithmsand Bayesian network approaches. Graph-oriented search algorithms have beenused to understand thestructure of networks,e.g. triangles in a net-work topology. Othermethods relate todynamic systems the-ory, e.g. stability ofcomponents, and alsomathematical methodsrelating to observablefeatures like robust-ness. Biological systemsare often extremelyrobust, that is they are self-maintainingunder external pressure.

Uninet’s expected influence

Because of its interdisciplinary approach,Uninet expects to be able to offer insightsinto significant new areas of research. Inpharmaceuticals, for example, analysis of

AT A GLANCE

Official titleUnifying networks for science and society

CoordinatorUK: University of Warwick

Partners• France: Centre National de la Recherche

Scientifique (CNRS)• Germany: European Media Lab

(EML Research)• Germany: Universität Bonn• Israel: Weizmann Institute• Spain: Science Research Council

(CSIC Sevilla)• Spain: University of Gerona

Further informationDr Markus KirkilionisMathematics Institute, University of WarwickCoventry CV4 7AL - UKFax: +44 247 652 4182E-mail: [email protected]

Duration36 months





The project’s work willbring out commonaspects so that mod-els can be reduced incomplexity to the sim-plest mathematicalabstraction.

U N I N ET



T he emerging field of glycomics – thesystem-wide study of the function of

sugars in an organism – is revealing thatsaccharides play multiple roles in a hugenumber of cellular processes. Consequently,pharmaceutical companies are increasinglyinterested in incorporating sugars into mod-ern therapeutics.But today only a handful of approved drugsinclude any functional saccharide groups.The industrial synthesis of even some simplemonosaccharide units is complex, and anoligosaccharide of just five units may involvemore than 50 separate process steps. Inshort, the production costs are frequentlyjust too high.

A natural solution

Living cells, meanwhile, manufacture,metabolise and manipulate sugars with ease,thanks to enzymes. Scientists are thereforekeen to harness this enzymic approach asan alternative to the inefficient and waste-ful synthetic processes used today.The EuroBioSyn project has set itself thechallenge to develop a cell-based systemto produce dihydroxyacetone phosphate(DHAP)-derived monosaccharides for pharma-ceutical applications. The team will convert

Industrial methods to manu-

facture even simple saccharide

structures are extremely com-

plex and expensive. Living cells,

meanwhile, readily synthesise

saccharides using enzymes. By

blocking unwanted metabolic

pathways and engineering the

regulatory properties of key

enzymes in bacterial cells,

scientists hope to convert

bacteria into highly efficient,

environmentally friendly and

economic saccharide factories

– and proving the possibility of

using bacteria for the economic

manufacture of many other

complex molecules.

the common bacterium E. coli into a ‘DHAPfactory’ capable of efficiently synthesisingthese monosaccharides on a commercialscale.The idea is to allow an engineered E. coli tohave an initial growth phase, then flip aswitch (through the introduction of a bacter-ial virus, or phage) that will cause a majorreorganisation of the cell proteome. In theproduction phase, the cells are reduced totwo main metabolic pathways which carry outsynthesis and provide energy.

Cutting out the clutter

In nature, cells are not geared to the pro-duction of high yields of a single product.Consequently, two highly efficient moduleswill be generated by optimising the activityof the key pathway enzymes and blocking allother unnecessary metabolism. EuroBioSynbrings together experts – experimental andtheoretical – in molecular biology, func-tional genomics, computational biology,biochemical engineering, and process sys-tems engineering. Together the team willbe able to analyse carbohydrate metabol-ism in E. coli, identify target enzymes foralterations, and optimise the pathwayperformance.

A sweeter way to make saccharides

E U ROB IOSYN

Developing artificial methods to produce saccharides is a challenging way to replicate nature.© Roche 2005S Y N T H E T I C B I O L O G Y

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The project aims to open up new, cost-effective production methods for the pharmaceutical industry.

The taste of success

If the EuroBioSyn project is successful it willimmediately solve the problem of economicproduction of DHAP derivatives at a com-mercial scale. The monosaccharides could beproduced cheaply from glucose in a one-

pot, one-step process,opening the way for newand more effective phar-maceutical products.However, the proof ofconcept with this rela-tively simple systemcould also lead the wayto the development offurther modules in thesystem, for example amodule for saccharideactivation and coupling

into more complex oligosaccharide structures.The revolutionary and environmentallyfriendly technology could be adapted forother complex molecules such as oligopep-tides and glycoconjugates, providing Europeconsiderable competitive advantage in thesector of fine chemical manufacturing.

Bioinformatics tools from the field of sys-tems biology, for instance, can identify whichenzymes in side reactions consume inter-mediates and lower yields. The genes formany of these non-productive enzymes canbe knocked out, but some of these enzymesmay be required for the initial growth phase.These need to be elim-inated during a pro-teomic switch from thegrowth phase to theproduction phase.Studies on the fate ofintermediates of thesepathways will providedata on the productiondynamics. System analy-sis will help to producea mathematical modelof the dynamics of thecomplex reaction sequences to identify, thenoptimise, any productivity constraints in theprocess. Computational biology can be usedto identify ways to modify the regulatoryproperties of key enzymes in these path-ways to allow for improved yields, whilstconserving their catalytic functionality.

AT A GLANCE

Official titleA modular platform for biosynthesis of complex molecules

CoordinatorSwitzerland: Swiss Federal Institute of Technology Zurich

Partners• Germany: Stuttgart University• Denmark: Technical University of Denmark• Spain: National Biotechnology Centre

Further informationProf. Sven PankeSwiss Federal Institute of Technology ZurichInstitute of Process EngineeringSonneggstrasse 5CH-8092 ZürichFax: +41 44 632 1325E-mail: [email protected]

Duration36 months





Scientists are keen toharness the enzymicapproach as an alter-native to the ineffi-cient and wastefulsynthetic processesused today.

E U ROB IOSYN



The use of antibodies in research is nowroutine, used daily in life-science labora-

tories across the globe. Yet despite theirprevalence, antibody production still relieson a 30-year old technique that is time con-suming and expensive: each time you wanta new monoclonal antibody you have to startfrom scratch. Furthermore, antibodies devel-oped this way are not suitable for humantherapeutics.A group of researchers from Germany,France, Austria and the Czech Republic hasembarked on an ambitious NEST project todevelop a new technology, which could dra-matically reduce the time and effort requiredto produce monoclonal antibodies. The Hyblibconsortium hopes to produce a ‘library’ ofaround one million hybridoma cells, eachexpressing a different antibody. It wouldthen be relatively easy for researchers toscreen the library and pick the cells thatselectively bind their chosen antigen.

Stocking the library

The hybridoma library will be produced byrearranging the genes that code for antibody

European scientists are combin-

ing their expertise in immun-

ology and molecular biology

to develop a new technique

for producing monoclonal anti-

bodies, aiming at a library of

over one million cells each

expressing unique antibodies.

A novel screening technique,

based on cell signalling, should

enable cells that specifically

bind antigen to be selected

and purified. A phenomenon

called somatic hypermutation

could further improve antibody

affinity. If successful, the Hyblib

system would be quick, easy

and far less expensive than

existing techniques, and could

become the standard produc-

tion method of the future.

specificity (the variable antibody genes),through the targeted action of enzymescalled recombinases. Each rearrangementof the genes produces an antibody withdifferent binding specificity, and in total willgenerate a population of cells – the library.The library would contain over one millioncells each expressing a different antibodywith different antigen specificity. It is there-fore likely that within the library an antibodycan be found with at least low to mediumaffinity for almost any target antigen.However, while you are likely to find cellsexpressing an antigen-specific antibody, itis unlikely that the binding affinity is partic-ularly high. A second strand in the project willtherefore develop a method to increase theantibody affinity once a suitable candidatehas been selected from the initial libraryscreen.Changes in antibody-antigen binding affin-ity are caused by mutations in the variableantibody genes. Research has shown thatcertain enzymes are capable of inducing thesemutations in cells in a process called somatichyper-mutation. The Hyblib researchers willtherefore insert genes for these enzymes so

Monoclonal antibodyproduction made quickand easy

HYB LI B

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S Y N T H E T I C B I O L O G YThe project will develop a new method to produce antibodies

without the need to use animals. © VIB 2005

In this novel library screening method noanimals are needed. Screening the librarywould be a relatively cheap and simple pro-cedure, especially as each hybridoma celldisplays over 100 000 antibodies on its sur-face, giving a strong signal for antigen bind-ing. Furthermore, as the entire library wouldbe descended from a single cell, background‘noise’ in the screening process would be

markedly reduced, alongwith the number of falsepositives.Although each individualtask in this projectinvolves standard molecu-lar biology procedures,the combined expertisein this project has thepotential to produce anentirely new system formonoclonal antibodyproduction. It has the

potential to dramatically speed up the gen-eration of monoclonal antibodies for appli-cations in basic research, diagnostics andeven human therapeutics.

that once a candidate cell has been selectedfrom the library, the hyper-mutation genescan be turned on. From the resulting mixtureof mutated cells, the rare ones expressinghigher-affinity antibodies can be selected.

Screening made simple

This hybridoma library method has manyadvantages over theconventional hybridomamethod for monoclonalantibody production.First, it is a library ofhuman antibodies. Thisis a major breakthroughas attempts so far togenerate human mono-clonal antibodies (whichare proven to be of thera-peutic use in patients)from hybridoma cellslargely failed. At present ‘human’ monoclon-als can be produced either via a laboriousgenetic engineering process to graft partsof the mouse antibody into the human anti-body scaffold, or by using patented trans-genic mouse strains.

AT A GLANCE

Official titleHuman monoclonal antibodies from a libraryof hybridomas

CoordinatorGermany: German Cancer Research Centre

Partners• Austria: Eucodis• Czech Republic: Academy of Sciences of

the Czech Republic• France: French Institute of Health and

Medical Research• Germany: Göttingen University

Further informationDr Frank BreitlingGerman Cancer Research CentreDepartment of Molecular Genome AnalysisIm Neuenheimer Feld 580D-69120 HeidelbergFax: +49 6221 421744E-mail: [email protected]

Duration48 months





“The combined expert-ise in this project hasthe potential to pro-duce an entirely newsystem for mono-clonal antibody pro-duction.”

HYB LI B



Cell mutation can produce much higher antibody affinity.

M any new biotechnology businessesrely on the use of live cells as pro-

duction units for proteins of commercialvalue. In such processes, a carrier and deliv-ery system introduces the gene coding forthe protein, with appropriate regulatorysequences, into the host cell. Althoughwidely applied, this method has drawbacks:it has to be optimised for each carrier anddelivery system, over-production of the pro-tein may be harmful to the cell, and purifi-cation may be problematic, particularly ifthe end product is intended for therapeuticuse and subject to strict regulatory require-ments.A solution may lie in the use of cell-freesystems for transcribing genes and trans-lating the transcripts into proteins. Thesesystems tend to have a rather low yield, butif the reactions are carried out under condi-tions of continuous flow (immobilisationof large molecules in a porous material, con-tinuous supply of reagents and removal ofreaction products), it is possible to achievea fairly constant rate of protein synthesisover a period of up to 100 hours.The time may be ripe for looking at DNA-based protein synthesis in a new way: howabout creating combinable artificial or semi-biotic modules capable of carrying out their

A European consortium aims

to develop self-assembling

particles capable, like the

nuclei of living cells, of sus-

taining gene transcription. This

function would be controllable

by non-biological signals trig-

gering DNA compaction loos-

ening. Implanted into cells or

interfaced with cell-free tran-

scription-translation kits or

synthesis-on-a-chip systems,

the particles, called ‘neonuclei’,

should offer an exciting new

approach to the production of

biomolecules of industrial or

medical interest.

different steps in a controlled manner? Todaythis is just a dream, but pioneers within theNEST Synthetic Biology PATHFINDER initia-tive have begun to pave the way. In a projectcalled Neonuclei, a multidisciplinary consor-tium aims to create self-assembling tran-scription-competent DNA-based modules,to be integrated into semibiotic systems forproducing complex biomolecules.

Neonuclei

The primary goal of the Neonuclei project isto generate synthetic analogues of cellnuclei, capable of self-assembly in mixturesof DNA, macromolecules (or nanoparticles),and lipids. The resulting ‘neonuclei' will con-tain a synthetic ‘genome’, and their internalnano-architecture should be able to sustaingene transcription in the presence of thenecessary enzymes and transcription fac-tors. Beginning with simple model systemsand building up to structures of increasingcomplexity, partners will focus on nano-structures formed in DNA-protein-lipid sys-tems as a result of phase separation. Studieson real nuclei will guide their efforts.The neonucleus ‘genome’ will offer an attract-ive novel feature: controllability of transcrip-tion by non-biological signals. The strategy

Synthetic analogues of cell nuclei

N EON UCLE I

Cell nuclei are capable of producing proteins.© InformationsSekretariat Biotechnologie 2005S Y N T H E T I C B I O L O G Y

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The project aims to produce synthetic versions of living cells.

New avenues

If successful, the project should yield novelcell-free expression systems where theneonuclei are used with reagent mixturesof biological origin, lab-on-a-chip type systemswhere the neonucleus is integrated withprotein synthesis modules on a microfluidicdevice, and implant-modified cells where

synthesis of target pro-teins can be switchedon and off as desired.Neonuclei should thuspave the way for thedevelopment of semi-biotic systems as a newarea of R&D.The long-term impact ofthis project could be

considerable. Potential applications ofneonuclei include, among others, safer genetherapy strategies, closed-loop devices forpatient treatment (synthesising complexbiomolecules on demand), and devices orsensors using unstable – but regenerable –biomolecules.

for achieving this is based on the observa-tion that in real nuclei, some genomic regionsare ‘silent’ because the chromatin (i.e. theDNA-containing material) is too compact toallow transcription. Hence, in addition toseveral genes (or repeats of the same gene)and appropriate regulatory sequences, theengineered genome will contain sequencesdesigned to induce (reversible) DNA com-paction in response tophysical or chemicalstimuli.As gene transcription isonly the first step in pro-tein synthesis, proof ofconcept will rely oninterfacing the neonu-clei with systems thatcan translate gene tran-scripts into proteins. These will include con-tinuous-flow transcription-translation kitsand prototype ‘synthesis-on-a-chip’ systems.In addition, the neonuclei will be micro-injected into living cells.

AT A GLANCE

Official titleSelf-assembly of synthetic nuclei: key modules for semibiotic chemosyntheticsystems

CoordinatorUnited Kingdom: University of Southampton

Partners• Sweden: Lund University• Sweden: Chalmers University

of Technology• Portugal: University of Coimbra• Germany: Ludwig-Maximilians-Universität

Further informationProf. George AttardSchool of Chemistry, University of SouthamptonUniversity Road, HighfieldSouthampton SO41 0RE - UKFax: +44 23 8059 3781E-mail: [email protected]

Duration48 months





NEONUCLEI shouldpave the way for thedevelopment of semi-biotic systems as anew area of R&D.

N EON UCLE I



It is amazing to think that the powerful elec-tronics found in computers are actually

based on networks of extremely basic com-ponents: switches that turn on or off depend-ing on input variables. It is also amazing tolearn that scientists are now building simi-lar switches from DNA. By joining togethercarefully selected genes and regulatorysequences, researchers are able to constructartificial ‘circuits’ which are able to senseparticular conditions or signals within a cell,and respond accordingly.An EU-funded project is working to demon-strate the potential of such rationallydesigned gene networks for medical appli-cations. A number of European scientistshave joined together to design network mod-ules that can detect and possibly correctaberrant cellular function in cancer cells.The researchers have decided to focus theirresearch on the p53 signalling system. Thep53 system is able to detect damage to thecell and then tell it either to repair itself ordie. When the system goes wrong, however,cells do not respond properly to damageand cancer may occur. Indeed, the p53 path-way is implicated in almost all tumour types– in around 50% of tumours the p53 proteinhas been altered in some way so that it nolonger functions correctly. The remaining

By carefully linking certain

genes and regulatory sequences,

scientists are able to design

and construct ‘gene networks’

that can sense and respond to

specific conditions or signals in

the cell. A multi-disciplinary

team is working to develop one

such network that will sense

errors in p53 signalling – a

pathway implicated in almost

all cancers – and respond either

by killing the cell or by actually

repairing detected mutations.

The technology could have a

wide range of applications from

gene therapy to diagnostics.

50% of tumours carry alterations either indirect regulators of p53 or in pathways thateventually lead to p53 activation.The primary objective of the NETSENSORproject is to build a gene network that willdetect several steps in the p53 pathway,identify the step that is not working correctlyand then selectively respond, either by killingthe cell or by repairing a mutant gene, if thisis the case.

Networks of knowledge

The development of this novel systemrequires the expertise of a multidisciplinaryteam. The project includes leading scien-tists from three laboratories and one SMEwith expertise in systems biology, proteindesign, cell biology, cancer therapeutics,viral delivery of genetic constructs, and DNArepair mechanisms. The first task of the group is to constructartificial networks that can sense the stateof the p53 pathway in cells, building onprevious work in this field by various part-ners. Numerous network modules will bedesigned and tested both experimentally(in a variety of p53 aberrant cell lines specif-ically produced within the project) and byusing computer modelling. By exchanging

Genes join up to detect and defend

N ETS E N SO R

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Gene networks could detect and possibly repair cancerous cells.S Y N T H E T I C B I O L O G Y

Computing power is critical to developing gene networks.

can be manipulated easily and will be cap-able of storing and delivering a wide rangeof different network constructs. They willalso ensure that the virus system can deliverits load to all cell types, but remain inactive

and not induce cell deathin healthy cells.

Sense of achievement

The culmination of thethree-year project willbe the testing of the net-works to detect and

respond to p53 aberrations in a selectionof tumour cell samples. NETSENSOR willdemonstrate that simple gene networkscan sense errors in complex cell signallingpathways and react to them. Such systemscould have widespread medical use in diag-nostics, drug delivery, highly targeted treat-ments and gene therapy. And from thesesimple networks perhaps one day medicinewill have a tool as powerful as our computersare today.

components from simple networks thatsense a single condition (e.g. high activity ofa protein that triggers p53 degradation) itshould be possible to create more compli-cated circuits that are able to detect andrespond to a variety of‘p53 errors’.Killing a cell is a rela-tively straightforwardaffair, but selectivelyrepairing damaged DNAis far more tricky. Theproject focuses on afamily of enzymes calledendonucleases whichare able to cut DNA at specific recognitionsites. This cutting opens up genes for repair,making it possible to replace mutant sectionswith corrected sequences. The NETSENSORproject will combine computational biologyand a process called molecular evolution toengineer endonucleases that recognisemutant DNA sequences that are known toinduce cancerous cells.The viral delivery of gene networks to cellsmust also be addressed. NETSENSOR par-ticipants will work to develop a vector that

AT A GLANCE

Official titleDesign and Engineering of gene networks to respond to and correct alterations in signal transduction pathways.

CoordinatorGermany, European Molecular Biology Laboratory

Partners• France: Cellectis• Germany: Medical School Hannover• Spain: Centro Nacional de Investigaciones

Oncológicas

Further informationProf. Luis SerranoEuropean Molecular Biology LaboratoryStructural and Computational BiologyMeyerhofstrasse 1D-69117 Heidelberg, DEFax: +49 622 1387 306E-mail: [email protected]

Duration36 months





Killing a cell is a rela-tively straightforwardaffair, but selectivelyrepairing damagedDNA is far more tricky.

N ETS E N SO R



Engineers and designers often takeinspiration from nature. Whether it is

self-cleaning paint, Velcro or morphingaeroplane wings, many technologicaladvances are based on designs that haveexisted in the natural world for millions ofyears. Recognising nature’s incredibleengineering and problem-solving skills,scientists often integrate aspects of biologyinto their research projects. Indeed, entirescientific disciplines are emerging thatmerge biology with previously unrelatedfields such as electronics.

Synthetic biology is one of these newdisciplines, using biological research in awide range of technology and engineeringapplications. The idea is to design andproduce simple biological componentsthat can be ‘plugged together’ like elec-tronic parts. These constructed, artificialsystems do not exist in the natural world;they are designed for specific functionsranging from protein engineering tocomputation.

Looking for details

Only a small number of research centres,mainly outside Europe, explicitly use the

Synthetic biology is an emer-

ging scientific discipline, but it

is unclear exactly what research

in this area is taking place in

Europe. SYNBIOLOGY aims to

identify the organisations where

synthetic biology research is,

or could be, taking place. By

surveying key stakeholders in

Europe and North America, the

project intends to discover the

main drivers and barriers for

effective research and for de-

veloping this discipline further.

Findings will be communicated

to national and European policy-

makers so they can consider

how to build Europe’s strengths

in this field.

term ‘synthetic biology’ to describe theirwork. Yet Europe has a wealth of expertise inmolecular biology, genetics, mathematics,and other disciplines which form the foun-dations for synthetic biology research.

In fact, some synthetic biology is certainlytaking place in Europe, scattered betweena host of different organisations. This frag-mentation means that the overall state ofresearch and its future potential acrossEurope is unclear. The SYNBIOLOGY projectwill therefore conduct the first-ever surveyof this new discipline. It aims to qualify thekey attributes of synthetic biology researchin Europe and North America, and identifydifferences across European countries, theUSA and Canada. From this analysis itshould be possible to highlight variousfactors, such as funding mechanisms, thatcould impact the level and nature of researchin this area and its short- and long-termcommercial possibilities.

The project consortium is made up of tworesearch and innovation consultancies, asynthetic biology company and a US univer-sity. Together they will first attempt to iden-tify all the existing and potential actors insynthetic biology research (e.g. universities,

A European perspectiveon synthetic biology

!

SYN B IOLOGY

S Y N T H E T I C B I O L O G Y

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The project aims to provide the ‘big picture’ of synthetic biology in Europe and North America. © Thomas Jones

respective countries. They are ideallypositioned to communicate the findings ofSYNBIOLOGY to the national policy-makerswho may have influence over the future oftheir country’s synthetic biology research.

The results of this project will also be usedby the Commission. The project will high-light how European policy and fundingoptions could also support the develop-ment and maximise the effectiveness ofthis research domain.

Questionnaires and surveys do not looklike the kind of ground-breaking, high-riskscience usually associated with NEST

projects.Yet SYNBIOLOGYhas the potential toproduce a far-reachingimpact on the futureof synthetic biology inEurope. Its insightswill give national andEuropean policy-makersessential informationfrom which they canbase their plans to build

up synthetic biology research to supporttechnological progress in the 21st century.

research institutes, research companiesand production companies) along withtheir geographic distribution. A selectionof key stakeholders – leading individualsrepresenting the synthetic biology researchcommunity, industry and government – willthen be contacted for more details onthe nature of the research, how it is dis-seminated, and what funding and supportservices are currently available.

Building a framework

SYNBIOLOGY is a support action comple-menting the more technology-focusedprojects within the NEST Synthetic BiologyPATHFINDER initiative.As such, it aims to pro-vide the ‘big picture’of synthetic biologyin Europe and NorthAmerica, and show howthis emerging sciencecan be fostered, encour-aged and strengthened.

At the national level,for example, key stakeholders will act asthe primary ‘disseminators’ within their

AT A GLANCE

Official titleAn Analysis of Synthetic Biology Research in Europe and North America

CoordinatorPortugal: Sociedade Portuguesa deInovação, S.A.

Partners• Greece: Centre for Economic Research

and Environmental Strategy• Germany: ATG:Biosynthetics• USA: University of Maryland Baltimore

County

Further informationProf. Augusto Eduardo Guimarães de MedinaSociedade Portuguesa de InovaçãoConsultadoria Empresarial e Fomento de InovaçãoRua de Júlio Dinis 242-2º-208 4050-318 PortoPortugalFax: +351 22 609 91 64E-mail: [email protected]

Duration15 months

Project Cost€ 226 200

EU Funding€ 226 200

Project referenceContract No. 15357 (NEST)


Synthetic biology aimsto design and producesimple biological com-ponents that can be‘plugged together’ likeelectronic parts.

SYN B IOLOGY



Entire scientific disciplines are emerging combining biology with previously unrelated fields such as electronics.

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