REPORT · p 5 2017 report - institut pasteur de lille a foundation on the move 58 support a major...

2017 REPORT

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foundation recognized of public utility since 1898

Vivre mieux plus longtemps

General Director of Institut Pasteur de Lille

Patrick Berche

Longevity.In 2017, Institut Pasteur de Lille, a private state-recognised public-interest foundation, consolidated its strategic positioning on longevity with its Interdisciplinary Centre for Research in Longevity, the development of its Disease Prevention Centre on the themes of Health and Longevity and the creation of a Regional Pollution Health Longevity Centre. These three activities pursue a single objective: increasing the life expectancy in good health of people, in order to live better for longer time.

The six joint research units at the Longevity Research Centre are working together to better understand the mechanisms of diseases that prevent healthy ageing, such as Alzheimer's disease, diabetes, cancer as well as infectious diseases. With about 350 scientific publications in 2017, Institut Pasteur de Lille is a major player in scientific research on longevity at a national and international level.

In addition to the research, the institute's Disease Prevention Centre gathers the health check-up, nutrition, vaccination and training activities. This centre can also take care of the most vulnerable people, gives them advice and directs them towards good treatments. Soon, the "Longevity Check-Up", in partnership with the Lille University Hospital and the Lille University, will offer Longevity medical content with a combination of tests for detecting cognitive activities, presbycusis, vision, osteoporosis and in-depth biological examinations to assess the physiological age of a person.

Finally, the new Regional Pollution Health Longevity Centre gathers together teams from Institut Pasteur de Lille and the Hauts-de-France region involved in the study of the impact of pollution on health (air pollution, nanoparticles, endocrine disruptors). The aim is to set up joint research projects on the issues of pollution and ageing.

For the Foundation, the link with the economic and industrial world is fundamental. In this regard, the statutes of Institut Pasteur de Lille have changed this year, with a new board of directors, which now incorporates personalities from the business sector.

To build the Foundation of tomorrow, the generosity of the public through donations and bequests as well as corporate sponsorship are crucial. Advances in research and health initiatives are only possible through the excellence of the teams, the commitment of the management and the support of our partners, donors and corporate sponsors.

A big thank you to them and to everyone who will join us this year to gain ground in the fight against diseases.

PASTEUR DE LILLEEDITORIALINSTITUT

2017 Activity report

Design anD proDuction: communications anD sponsorship Department - institut pasteur De LiLLe

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p 5 2017 REPORT - INSTITUT PASTEUR DE LILLE

58A FOUNDATION ON THE MOVE

52SUPPORT A MAJOR PROJECT ON LONGEVITY

48UNDERSTANDING THE IMPACT OF POLLUTION ON HEALTH AND QUALITY OF LIFE

40BETTER LIVE TODAY IN ORDER TO AGE WELL TOMORROW

18UNDERSTANDING DISEASES & INVENTING THE TREATMENTS OF THE FUTURE

8OBJECTIVE: LONGEVITY

6HIGHLIGHTS

CONTENTS

centre for reseArch on Longevity

reseArch teAms technoLogy pLAtforms Biotechs

prevention services – heALth – Longevity

poLLution heALth Longevity centre

fund rAising 2017-2022 sponsorship cAmpAign

new museum of institut pAsteur de LiLLe

the BoArd of directors

the orgAnisAtion chArts heAdcount

An orgAnisAtion undergoing trAnsformAtion

Key figures

csr commitment

empLoyment/resources

66SCIENTIFIC PAPERS

70PARTNERS AND SUPPORT

INSTITUT PASTEUR DE LILLE - 2017 REPORT p 6

Launch of the 10th Kid Campus event

FEBRUARY MAYMARCH JUNE

HIGHLIGHTS

Support for the Foundation of Franck Thilliez for the release of his book "SHARKO"

Eco-Campusday for the European Sustainable Development Week

Pretty Month of Europe (Joli mois de l'Europe in French) laboratory open days

19th Nutrition Interviews

Horizon Campus #2017Campus staff day

1st Smart Move Challenge (Challenge Bougeons Malin in French) event with Kiabi

3rd Scientific Day sponsored by the Institut Pasteur de Lille

Tuberculosis drug prototypeSmart 420


SEPTEMBER NOVEMBEROCTOBER DECEMBER

Opening of the new Museum of Institut Pasteur de Lille

Participation in 2017 MobilityChallenge ("Best active mode rate" category winner)

1st "SOLID'AIR" event in partnership with WEEMBI

Signature of a framework agreement with the Oswaldo Cruz Foundation (Fiocruz, Brazil)

Auchan Retail France's commitment to the Institute

Verspieren's commitment to the institute

16th Nutrition workshops

Longevity Conference open to the general public at Lille Grand Palais

2nd International Longevity Symposium

HIGHLIGHTS

Heart surgery discovery

Participation in the second Youth Forum

1st Longevity University Diploma year group

2nd Public Health Innovation Day

1st regional meetings on "pollution, health and quality of life"

1st At the heart of the labs (Au cœur des labos in French) event


OBJECTIVELONGEVITY


The number of people over 85 will double over the period from 2005 to 2020. According to various hypotheses concerning fertility, mortality and migration, the number of dependent people is constantly increasing. It is not only a medical problem, but also a political one, with major socio-economic repercussions for the organisation of society and the treatment of the elderly in particular. Some countries have managed to drastically reduce the dependency period. This is possible thanks to a disease prevention policy to combat the major diseases associated with ageing which are important causes of mortality after the age of 65 years.

As a major scientific player in the Hauts-de-France region with an international reputation, Institut Pasteur de Lille supports the medical world as well as civil society and the business community, to take up the challenge of the century: living healthier for a longer time. In this way, it dedicates the results of its work to research and disease prevention in health care. It also plays a role on behalf of the economy and of innovation through its platforms and biotechnology start-ups.

Currently, more than 800 people with 30 different nationalities work on the campus, including the 330 employees of Institut Pasteur de Lille, 6 research units spread across 50,000 m2 of laboratory space, 10 advanced technology platforms, a disease prevention centre that conducts 15,000 health checks and more than 26,000 vaccinations per year.

In 2017, Institut Pasteur de Lille consolidated its position on the issue of longevity by creating the Centre for Health and Longevity and the Pollution Health Longevity Centre, a centre of expertise on the impact of pollution on health. The Longevity Research Centre relies on its 33 teams of researchers to develop scientific knowledge in the diseases associated with ageing and contribute to the development of new disease prevention tools and treatments with the aim of extending the period of life in good health after the age of 60 in order to live better for longer.

A CENTER OF EXPERTISE ON LONGEVITY

ReseaRch centeR

on Longevity

PReventioncenteR foRheaLth and Longevity

PoLLution- heaLth- Longevity

centRe

In 2050, in metropolitan France, 1 person in 3 will be over the age of 60 years

In 2017, at the age of 60, French women can, on average and according to several hypotheses, hope to live another 27.3 years and men, another 22.9 years.

Between 1996 and 2016, the percentage of people over 65 in the population increased from 15.1% to 18.8%.



centRe foR ReseaRchon Longevity

The teams of the Institut Pasteur de Lille, in partnership with the Lille University, Inserm, CNRS, and the Lille University Hospital, carry out research on diseases related to ageing at the Longevity Research Centre. The objective: to understand the diseases that prevent us from ageing well in order to slow down their development, create the treatments of the future and modify behaviour.

• Cardiovascular diseases• Metabolic diseases, diabetes, obesity• Neurodegenerative diseases• Inflammatory diseases• Infectious diseases• Cancers

centRe foR heaLth and Longevity

Combining research and disease prevention activities, the Disease Prevention Centre of the institute has an innovative approach that is unique in France, for disease prevention and health education, counselling and support for active and successful ageing, aimed at detecting the risk factors of age-related diseases and providing advice and tools to mitigate the consequences.

• Innovative longevity health check-ups based on tracking and screening tools developed by the best specialists in partnership with the Lille University Hospital and the Lille University

• Personalised coaching (nutrition, physical activity, social activity, etc…)

• An international vaccination centre• A Nutrition Department• Studies and research• Conferences and events open to the general public• A training department

PoLLution heaLth Longevity centRe

The Health Pollution Longevity Centre was opened in 2017 at the instigation of experts in the field to develop a research programme aimed at understanding the impact of pollution on health and longevity. The Institut Pasteur de Lille offers expertise in the field of environmental pollutants and their toxicity, particularly that of nanoparticles on the respiratory tract.

• Genetic toxicology: expertise in the field of general toxicity of nanoparticles that is without equal in France

• Microbiological safety: research on micro-organisms that are emerging in the environment


Although the objective of leaving healthier for longer time may seem modest, it is actually very ambitious. This centre, which gathers teams from Institut Pasteur de Lille, Inserm, CNRS, the Lille University and Lille University Hospital, focuses its research projects on the following 2 main objectives: objective 1 "Longevity, genes anD environment" objective 2 "Longevity, immunity anD inFection"

The cross-disciplinary approach – genetics, biochemical, cellular, clinical, epidemiological, public health, etc. – will be used to identify candidate genes that will open up opportunities for discovering new biomarkers that will be tested on those populations which are at risk, as well as new medicines by molecular screening. Indeed, the early prevention of diseases before the emergence of the clinical symptoms can considerably improve the quality of life and delay the handicaps associated with ageing.

Longevity and Research

By 2060, 1 in 3 French people will be over 60, i.e. an increase of 10.4 million between 2007 and 2060.

In 2016, the average French life expectancy at birth was 85.4 years for women and 79.3 years for men.



project nAme AppLicAnts project titLe

dReaM François Trottein/CIIL Hélène Duez/U1011

Impact of circadian clock dysfunction on innate immunity against respiratory infections

nash-LiP16ag Réjane Paumelle/UMR 8161Albin Pourtier/U1011François Pattou/UMR 1190

Role of p16 on lipid metabolism and senescence of hepatocytes

ePiPReteRM Philippe Froguel/UMR 8199Laurent Storme/EA 4489

Identification of epigenetic markers of age-related diseases in premature infants

senheaL Corinne Abbadie/UMR 8161Mathias Chamaillard/CIIL

Impact and regulation of the senescence of intestinal cells during the healing of intestinal lesions

toMis ageing David Montaigne/UMR 1011Benoit Deprez/U1177

Pharmacological prevention of myocardial ischemic injury by antagonism to the Rev-erb alpha clock gene: cardioprotection of the ageing heart

coLLABorAtive projects

In order to support interdisciplinary projects on longevity, Institut Pasteur de Lille is coordinating the CPER-CTRL programme for the 2016-2020 period (Interdisciplinary Centre for Research on Longevity) funded by the state, the Hauts-de-France Region, the Métropole Européenne de Lille (MEL) and the FEDER funds. The CPER-CTRL calls for projects aim to promote cooperation between teams in the region on new issues related to longevity as well as the emergence of new teams. Following the 1st CPER-CTRL call for projects launched in October 2016, 9 projects, including 4 exploratory and 5 collaborative projects, and 4 Post-Doc positions were selected for funding after evaluation by independent experts and by the International Scientific Advisory Board (ISAB).


toxoneuRo Mathieu Gissot/CIILJean-Charles Lambert/U1167

Neuronal modelling after toxoplasma infection

PRoactiv Ruben Hartkoorn/CIILNicolas Willand/U1177

Activation of prodrugs: new antibiotics

ideRceLL Rébecca Déprez-Poulain/U1177 Steve Lancel/U1011

Impact of the IDE modulation on the initiation of UPR in muscle and liver cells

fLaPP Corinne Grangette/CIIL Bart Staels/U1011

Exploration of the therapeutic potential of probiotics in preclinical models of fatty liver

expLorAtory projects

Results from the 1st 2016 CPER-CTRL call for projects


tiiMaging Anne Tailleux/UMR1011Julie Charton/Benoît Deprez/U1177

Neuronal modelling after toxoplasma infection

connecting Muriel Pichavant/CIILFlorence Pinet/U1167

Smoke inhalation and a poor diet: impact of oxidative stress on accelerated ageing

betaPRotect Amar Abderrahmani/UMR8199Oleg Melnyk/UMR8161

Effect of new MET antagonist to fight beta cell decline in type 2 diabetes

atheRovac Camille Locht/CIIL David Dombrowicz/U1011

Vaccination against atherosclerosis using a live vaccine against whooping cough

post-doc progrAmme



2nd collaborative and exploratory CPER-CTRL call for projects in 2017

In June 2017, Institut Pasteur de Lille launched the 2nd CPER-CTRL call for research projects. Each project submitted must be presented by 2 teams belonging to different units and responds to one of the 2 objectives of the Longevity research project. This call for projects will fund collaborative projects up to € 200,000 and exploratory projects up to € 50,000.

03/2018 03-09/2018

06/2017

LAunch

of the AAp

reception of

22 projects

evALuAtion

09/2017 to 02/201809/2017

2017 CPER-CTRL emerging team call for projectsIn June 2017, Institut Pasteur de Lille launched an "Emerging Teams" call for projects to attract new teams and skills, and consolidate and develop the research programme on longevity and ageing. The teams are called upon to develop ambitious and innovative research programmes and to build privileged relationships with the existing teams on the campus.Successful applicants will benefit from a three-year budget to create a new group to set up during the 4th quarter of 2018. They will have access to laboratory and office spaces, as well as the state-of-the-art technological platforms available on the campus of Institut Pasteur de Lille.

project stArt-up

exAminAtion

of the funding request

project seLection

process

10-12/2018

01-03/2018 03-09/2018

06/2017

LAunch

of the AAp

reception of

23 projects

seLection

process

12/2017 to 01/201811/2017

instALLAtion

of the teAms

exAminAtion

of the funding request

end of the

project seLection

process

10-12/2018

22 projects received

23 projects received

CPER-CTRL financingPr. Bernard Thorens, Interactive Genomics Center of LausannePr Folkert Kuipers, Groningen Longevity Research, CenterPr Miroslav Radman, Mediterranean Institute for Life Sciences MedILS, Split, Croatia

Pr Gordon Dougan, Wellcome Trust Sanger Institute, CambridgePr Thomas Thum, Hanover Medical School IFBPr Philip Scheltens, Alzheimer Center, Amsterdam

An International Scientific Advisory Board



Support for shared technological platforms

Institut Pasteur de Lille is one of the three major Biology and Health Platform within the Lille agglomeration (with the university-hospital campus and the campus of the University of Villeneuve d'Ascq). The platforms are managed in partnership with the Lille University, the CNRS, Inria and Inserm.

The facilities include cellular imaging, transcriptomics, genomics, bioinformatics and bioanalysis, chemistry, pharmacology, proteomics and mass spectrometry, nuclear magnetic resonance, life imaging, experimental resources, etc. These exceptional tools, some of which are unique in France, attract researchers and industrial collaborations from all over France and abroad.These facilities aim to provide public and private research teams with unique expertise and a complete set of tools and skills that can be used to multiply the opportunities for collaboration.

In 2017, support for the platforms, which represent a unique portfolio of analytical capacity, was reflected in the acquisition of equipment and staff support for 3 of them:

bioiMaging centRe LiLLe - noRd de fRance (biceL), iMaging PLatfoRM ceLL and tissue

cytoMetRy

PRoteoMics - Mass sPectRoMetRy

nucLeaR Magnetic Resonance (nMR)



FOCUS ON… THE BILILLE PLATFORM

CPER-CTRL financing

Created at the instigation of the Lille University, in collaboration with Institut Pasteur de Lille, Inserm, CNRS, Inria and the Lille University Hospital, Bilille is one of the seven Biology-Health platforms of the Lille agglomeration that offers a range of diversified local services such as:

• access to intensive computational resources • expertise for the analysis of data and computer development• creation of workshops and courses on current topics• support in putting together collaborative projects involving data analysis

The platform specialised in bioinformatics, bioanalysis and biostatistics trains researchers in a methodology for analysing data and software. It also provides a meeting place for researchers and engineers to discuss the issues they are facing associated with their projects and research. This enables them to identify needs in the form of short projects (1 to 3 months).

In November 2017, the Bilille platform launched a call for projects called "engineer missions 2018" to draw up a list of the needs in terms of the engineering resources of agglomeration's Biology-Health research teams and laboratories.This call for projects covers the period from February 2018 to December 2018. Each mission can last from 1 to 3 months, and must fall within the scope of the platform's topic: bioanalysis, bioinformatics, biostatistics. For example, this could include testing tools, analysing data and small IT developments. This call for projects makes it possible to set up a logical plan of the available engineering resources on the platform, with a good correspondence between the projects and the skills profiles.

All the projects submitted by the Campus Pasteur Lille teams were accepted. A dedicated engineer, supervised by a Bilille researcher, will be available for each of the selected projects.

In 2018, Institut Pasteur de Lille will become a site of the Bilille platform by providing a dedicated office at Campus Pasteur Lille. The recruitment of an engineer, will strengthen the team of 5 engineers of the platform thanks to the CPER-CTRL.



In order to boost knowledge and provide innovative tools for fighting against diseases, scientists at the Institut Pasteur campus in Lille are developing transversal projects involving the different departments of the Institute as well as public and private partners, and they have initiated collaborations with the best experts all around the world.

New international strategic partnerships

The goal of this initiative is not only to build awareness about the institute and boost its appeal but also to develop its capacity to explore strategic funding opportunities around the world and respond to increasingly competitive international demands.

In addition to the scientific collaborations initiated by scientists in response to a specific project, the Institut Pasteur de Lille has set up institutional agreements with key partners:

• International Network of Pasteur Institutes: 33 institutes around the world• Lebanon: Lebanese University/Doctoral school (training)• Senegal: Espoir Pour La Santé (EPLS-NGO)• India: Associated Laboratory (LIA-SIGID)

The Institut Pasteur de Lille has also been designated as coordina-tor of the Longevity programme within the International Network of Pasteur Institutes.

The Institut Pasteur de Lille is studying potential new partnerships with universities or institutions that are seeking to establish scientific collaborations and that share the same values and missions.

More than 130 students on Master's or PhD programmes, of which about 12% are foreign students (2017), are trained each year in the laboratories of the campus of Institut Pasteur de Lille.

International relations

New development strategyThe objectives of Institut Pasteur de Lille are:

4 Adopting a leadership role internationally in the area of research in healthy ageing4 Collaborating with the best scientists around the world4 Exploring the sources of strategic funding around the world4 Increasing the visibility and attractiveness of the institute

In 2017 Brazil: Oswaldo Cruz Foundation (Fiocruz) (agreement signed in November 2017 with a view to developing collaborations in the field of neuroscience and longevity)

Structural organisation in progress Netherlands: University Medical Center Groningen Belgium: Vlaams Instituut voor Biotechnolgie (VIB) United States: Mayo Clinic, Rochester, Minnesota



On 13 & 14 December 2017, national and international experts presented their most recent results on several major topics at the 2nd International Scientific Longevity Symposium organised by Institut Pasteur de Lille:

4 Immunosenescence4 Immunity and neurodegenerative diseases4 Microbiota and ageing4 Inflammation and ageing4 Disease prevention and treatment of age-related diseases

The introductory lecture was given by Prof James Kirkland, director of the Robert and Arlene Kogod Centre on ageing at the Mayo Clinic, the American University Hospital and Research Federation. Prof James Kirkland presented very promising results on the development of treatments to eliminate the senescent cells that accumulate with ageing and in diseases such as dementia, atherosclerosis, cancers, diabetes and arthritis.The symposium concluded with the presentation of Dr John Beard, director of the Department of Ageing and Life at the World Health Organisation (WHO) in Geneva. The WHO has identified ageing as one of its priority areas of work. Dr Beard is the author of the first World Report on Ageing and Health published in 2015. At the symposium, Dr Beard presented the WHO's current reflection on ageing and health as well as the major global research and knowledge initiatives focusing particularly on low- and middle-income

countries, as well as the WHO's Global Network of Age-Friendly Cities and Communities, which now includes about 400 cities in 40 countries.

Symposium Longevity -13 & 14 December 2017



UNDERSTANDING DISEASES & INVENTING THE TREATMENTS OF THE FUTURE



Institut Pasteur de Lille today hosts a research centre divided into six units, with multidisciplinary, cross-cutting skills.

It is organized around the following axes:

Over the past ten years, these teams have endeavoured, together with their research partners, to get structured around excellence laboratories and facilities financed as part of the PIA (investment programme for the future), including:

Institut Pasteur de Lille's campus boasts an exceptional concentration of high level facilities and technology platforms whose mission is to serve all the researchers in the regional scientific community. It also has a large molecule library – the chemical library – where thousands of tests are conducted every year, helping in the discovery of new drugs.

Research excellence combined with a health approach to provide the best answers

infectious and infLaMMatoRy diseases

neuRodegeneRative diseases

caRdiovascuLaR diseases

MetaboLic diseases, diabetes, obesity canceR dRug discoveRy

centeR

a Labex dedicated to aLzheiMeR's disease (distaLz)

a Labex dedicated to studying diabetes (egid)

an centeR of infection and iMMunity (ciiL) invoLved in the PaRafRaPLabex

an equiPex dedicated to genoMics (Ligan-PM)

an equiPex dedicated to ceLLuLaR iMaging PhaRMacoLogicaL scReening (iMaginex bioMed).



This unit focuses on the fight against age-related diseases, especially cardiovascular and neurodegenerative diseases. Prof Philippe Amouyel coordinates Distalz laboratory of excellence (LabEx), dedicated to Alzheimer's disease. Three teams interact within UMR1167 on the "epidemiology and public health of cardio and cerebrovascular diseases", the "molecular determinants of heart failure and ventricular remodelling", as well as on the "molecular determinants of Alzheimer's disease and cognitive disorders".

Risk Factors and Molecular Pathways of Aging-Related Diseases

Pr Philippe Amouyel PU-PH, University Lille University HospitalU1167 - Distalz Labex Inserm, Institut Pasteur de Lille, Lille University Hospital, Faculty of Medicine, Lille University

Analyse the risk factors to improve the prevention of cardiovascular diseaseThis team led by Dr Aline Meirhaeghe analyses the role of cardiovascular risk factors (genetics, excess weight, obesity, type 2 diabetes, high blood pressure, cholesterol, smoking, etc.) in the emergence and progress of myocardial infarction and strokes. Their work is based on Lille's morbidity register of ischemic heart disease and stroke, which continuously inventories all cases of these diseases occurring within the Metropolitan Community of Lille. The purpose of these studies is: • to understand the evolution of vascular pathology in terms of classification,

management and prevention, • to analyze the role of genetic and environmental determinants of cardiovascular

diseases.

Detecte cardiac ageing in order to anticipate it more effectivelyFollowing a myocardial infraction, the left ventricle may change shape and the patient then suffers from heart failure: the heart is no longer capable of pumping enough blood to meet the body's oxygen demand. Dr Florence Pinet, who leads this team, is looking for the early markers of heart failure. Specialising in proteomics, a science that studies proteins and their functions and interactions within cells, it has developed a

protocol for clinical research at the patient's bedside that has made it possible to discover early biological markers of the remodelling of the left ventricle associated with heart failure. Since then, it has developed a dosage that can be used in clinical routines and help prevent the accelerated ageing of the heart.

Understand genetic susceptibility to Alzheimer's disease in order to combat it more effectivelyAlzheimer's disease is a neurodegenerative disorder of the brain that develops over several decades. So when the clinical signs appear, the disease has already done irreparable damage. The team led by Dr Jean-Charles Lambert is interested in the study of individual susceptibility to Alzheimer's disease and was able to identify the majority of the genes involved in the occurrence of this disease. This research should help to gain a better understanding of the causes in order to propose new treatment and prevention options.


By combining the results of the ELISABET study with the previous population-based studies done by the team, it was possible to assess the long-term increase in the frequency of cardiovascular risk factors between 1986 and 2013 in the Lille agglomeration. The proportion of overweight men did not increase the proportion of people with high cholesterol and high blood pressure dropped significantly during this period. The number of smokers also declined among men but remained stable among women. At the same time, heart attack mortality has dropped by 2.6% each year for men and 2.8% for women. This work illustrates the important contribution of disease prevention to the reduction of cardiovascular mortality in our region.Clement G, et al., Changes over time in the prevalence and treatment of cardiovascular risk factors, and contributions to time trends in coronary mortality over 25 years in the Lille urban area (northern France). Arch Cardiovasc Dis. 2017 Dec;110(12):689-699.

The progress towards heart failure is difficult to predict. By computer analysis, 13 miRNAs related to the 45 modulated proteins were identified in an experimental heart failure model. 3 miRNAs were validated: miR-21-5p, miR-23a-3p and miR-222-3p and their target SOD2, a major antioxidant enzyme that was increased in the heart and the plasma of the experimental model. This work has demonstrated that, in a cardiomyocyte culture, a molecule mimicking or inhibiting miR-222-3p respectively induces a decrease and an increase in expression of SOD2. The circulating levels of 3 miRNAs and SOD2 are associated with a deleterious cardiac remodelling in patients with myocardial infarction in the REVE2 study, showing the potential of 3 miRNAs and their target SOD2 as IC biomarkers .Dubois-Deruy E, et al. MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure. Sci Rep. 2017 Nov 7;7(1):14747. doi: 10.1038/s41598-017-15011-6.

The systems' biology analysis identified the molecular events involved in post-myocardial infarction left ventricular remodelling from "omic" data obtained in patients phenotyped for deleterious ventricular remodelling (REVE2 study). The analysis network built under Cytoscape from the 24 molecular variables of REVE2 contains 1310 molecules including 1263 proteins, 24 miRNAs, 22 metabolites and 1 long non-coding RNA, linked by 8639 interactions. This network has identified the mechanisms associated with remodelling after an infarction over time, such as structural changes in the heart and selection of new targets.Pinet F, et al.Integrative network analysis reveals time-dependent molecular events underlying left ventricular remodeling in post-myocardial infarction patients.Biochim Biophys Acta. 2017 Jun;1863(6):1445-1453.

Despite the many advances that have been made, the genetic component of Alzheimer's disease is not yet fully characterised. In this context, the international I-GAP consortium has set up a new study involving nearly 85,000 individuals based on the use of a new genetic analysis tool called the "exome chip". This work has highlighted three genetic determinants of the disease: TREM2, PLCG2 and ABI3. Remarkably, these three genes participate in the same protein network and are predominantly expressed in the microglial cells. The data indicates a major dysfunction of microglial cell function during the development of Alzheimer's disease.Sims R et al. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet. 2017 Sep;49(9):1373-1384.

After highlighting new genetic determinants of Alzheimer's disease, it is necessary to understand their roles in the patho-physiological process leading to the disease. To this end, the team set up a cell imaging tool that made it possible to study the under-expression of all the genes on a major element of Alzheimer's disease, the metabolism of the precursor of the amyloid protein. This approach based on a high information content screening has made it possible to select the genetic determinant FERMT2 as an important player in this metabolism.Chapuis J et al., Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism.Acta Neuropathol. 2017 Jun;133(6):955-966.

HIGHLIGHTS



Research in Pr Bart Staels' team is oriented to molecular pharmacology of diabetes and its cardiovascular complications. The unit particularly focuses on the regulation of the genes involved in these pathologies and the consequences of their deregulation, with a special interest in nuclear receptors which represent potential therapeutic targets, by using functional genomic and molecular pharmacology techniques.

Nuclear receptors, cardiovascular diseases and diabetes

Pr Bart Staels PU-PH - Lille University Lille University HospitalU1011 Inserm, Lille University, Institut Pasteur de Lille, Lille University Hospital

The energy homeostasis of the body is ensured by the close communication between the different organs by integrating numerous endocrine and metabolic signals. The imbalance of the

metabolism leads to dyslipidemias and diabetes which can lead to atherosclerosis and the development of cardiovascular diseases. During the year 2017, the work carried out within Unit 1011 led to the publication of some thirty articles in international journals, including a number of major publications.

The unit highlighted the importance of the circadian rhythm in controlling muscle mass as well as the response to stress, inflammation and in the circadian response to cardiac ischemia-reperfusion. The fibrotic role of PPARa-regulated dermatopontin has been demonstrated and that selective activation of PPARalpha improves dyslipidemia, reverse cholesterol transport and decreases inflammation and atherosclerosis.

The work of the unit in minipigs demonstrated that the increase in the concentration of systemic bile acids after RYGB (Roux-en Y gastric bypass) is due, at least in part, to a decrease in their hepatic uptake and that alterations in bile acid metabolism are associated with insulin resistance and not with NASH lesions in obese patients. As part of a collaborative effort, the team developed a TGR5 bile acid receptor agonist with an action that targets the intestine and that acts as a GLP-1 secretagogue in vivo and contributed to endothelial function studies showing, in mouse models, a differential effect of the CETP inhibitors as well as a beneficial effect of the manipulation of the gut microbiota by a diet enriched in non-digestible inulin-type fibres.

The researchers showed that the macrophages surrounding the calcification zones of human atherosclerotic plaques are incapable of degrading the calcium deposits. A pharmacological modulation of the macrophage differentiation may be a new therapeutic target for atherosclerosis-related complications. A transcriptomic

analysis identified targets of interest in aortic valve stenosis (AVS) that validates one of these targets of interest and the signalling pathway associated with this target (patent being drafted with Inserm Transfert). This work should lead to the identification of innovative pharmacological targets in this pathology. The researchers characterised the von Willebrand factor (VWF) as a biomarker of flow abnormalities in AVS-induced high shear cardiovascular disorders whose only effective treatment to date is valve replacement by surgery or by implantation of an aortic valve prosthesis. The result of these procedures is variable and their per-procedural evaluation is complex. The team has developed a new marker to identify the results of this procedure and has demonstrated that the abnormalities of VWF multimers can be used to identify per-procedural complications and to guide the treatment of the patients but also that these abnormalities affect the prognosis of TAVI procedures. This work continues with the study of the impact of the screening of abnormalities of VWF multimers on therapeutic decisions. Finally, the team demonstrated that these VWF abnormalities were present in patients with mechanical circulatory assistance, that they were modulated by the level of residual arterial pulsatility and impacted the risk of bleeding.

Preliminary results show that FXR regulates B cell function and its inactivation promotes the immunoregulatory potential of these cells. Researchers have shown that the inactivation of RORalpha within regulatory T cells increases the immunoregulatory capacity of these cells. In contrast, the inactivation of myeloid cells induces fatty liver and increased insulin resistance.

The team also demonstrated that the keratinocyte expression of tristetraspolin was an important regulator of psoriasis. FXR expression by platelets directly regulates their function.

The work is based on the assumption that the activity of RNs is controlled by the sequential recruitment of



corepressors and coactivators by the considered receptor, resulting in the formation of a multi-protein complex or interactome. The researchers have shown that the nature of this interactome conditions the ability of RNs to regulate the transcription of a set of target genes (or regulon) by direct or indirect binding to a set of DNA sequences, thus defining a cistrome and inducing epigenetic modifications of various kinds. These processes are altered by post-translational modifications under physio-pathological conditions and affect the signalling pathways controlled by the RNs. The team is seeking to specify the molecular mechanism(s) and their functional importance. The

properties of FXR, a bile acid receptor and regulator of lipid and carbohydrate metabolism and cholesterol, have been studied. The importance of PPARα in controlling cardiovascular and hepatic diseases including acute liver impairment (ALI) and more particularly NASH and fibrosis is being studied. Deregulations of an IncRNA expression in adipocyte differentiation was performed. The role of rev-erb-alpha and beta receptors in controlling metabolic activity is an emerging theme. This work contributes to an understanding of the biological activity of RNs and their utility as therapeutic targets.

Non-alcoholic steatohepatitis (NASH) is an active liver disease that can induce cirrhosis and liver cancer. The identification of non-invasive markers and new therapeutic targets can be done by a detailed study of the transcriptome of the human liver. The study provided a small but accurate inventory of these markers and targets, one of which, dermatopontin, was validated by pre-clinical studies.Lefebvre P., Lalloyer F., Baugé E., Pawlak M., Gheeraert C., Dehondt H., Vanhoutte J., Woitrain E., Hennuyer N., Mazuy C., Bobowski-Gérard M., Zummo F.P., Derudas B., Driessen A., Hubens G., Vonghia L., Kwanten W.J., Michielsen P., Vanwolleghem T., Eeckhoute J., Verrijken A., Van Gaal L., Francque S., Staels B.: Interspecies NASH disease activity whole-genome profiling identifies a fibrogenic role of PPARα-regulated dermatopontin. JCI Insight, 2017; 2, e92264.

Using functional genomics analyses that integrates data from cistromes, epigenomes and transcriptomes, this work characterised how the nuclear receptor Farnesoid-X-Receptor (FXR) uses different types of cis-regulatory elements to modulate the expression of ubiquitous cell maintenance genes on the one hand and that of genes more specifically for liver function on the other hand (metabolic homeostasis of the body). Differential use of promoter and enhancer type regulatory elements characterised by the recruitment of different modules of transcriptional regulators define a specific framework for FXR action in controlling these different gene clusters.Dubois-Chevalier J., Dubois V., Dehondt H., Mazrooei P., Mazuy C., Serandour A.A., Gheeraert C., Guillaume P., Bauge E., Derudas B., Hennuyer N., Paumelle R., Marot G., Carroll J.S., Lupien M., Staels B., Lefebvre P., Eeckhoute J. : The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions. Genome Res. 2017; 27, 985-996.

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Cardiac complications are less frequent and less severe when valvular surgery is performed in the afternoon rather than in the morning. This issue under consideration here is a modulation of the ischemia lesion by the molecular actors of the biological clock present in each of the cells of the heart. The shift of this internal clock by the suppression of the activity of one of its actors, the nuclear receptor, Rev-erba, reduces the significant susceptibility of the heart to ischemia observed in rodents in the waking period. These findings point to new therapeutic approaches in cardiac pathology, especially in the context of myocardial ischemia.Montaigne D., Maréchal X., Modine T., Coisne A., Mouton S., Fayad D., Ninni S., Klein C., Ortmans S., Seunes C., Potelle C., Berthier A., Gheeraert C., Piveteau C., Deprez R., Eeckhoute J., Duez H., Lacroix D., Deprez B., Jegou B., Koussa M., Edmé J.L., Lefebvre P., Staels B.: Day-time of peri-operative myocardial injury in cardiac surgery and its prevention by Rev-erb-α antagonism: a single-centre propensity-matched cohort and a randomised study. The Lancet 2017; Epub



Microbial infections and inflammatory diseases remain major causes of mortality and morbidity. Their long-term impact on other conditions, such as cancer, cardiovascular, metabolic and neurodegenerative diseases, is considerable. In order to understand infection and immunity, including its deregulation, integrated multi-disciplinary approaches are required. These are developed among the 14 complementary teams of the Centre for Infection and Immunity of Lille (CIIL).

Center of Infection and Immunity of Lille (CIIL)

Dr Camille Locht Inserm research directorUMR 8204 - U1019, CNRS, Inserm, Lille University, Institut Pasteur de Lille

The 14 teams from CIIL bring together more than 230 researchers, engineers, and technicians with complementary expertise covering a wide range of disciplines, from molecular epidemiology, virology, bacteriology and molecular and cellular parasitology, to the immunological bases of infectious and non-

infectious diseases and the development of clinical applications. Specifically, scientists are looking for treatments for tuberculosis and in particular for multi-resistant and ultra-resistant tuberculosis, hepatitis C, malaria, bilharzia, plague, toxoplasmosis, pertussis, inflammatory diseases, whether intestinal or pulmonary (asthma,

respiratory allergies, chronic bronchitis, chronic obstructive bronchopneumonia). The 14 teams are divided in three major fields: parasitology, molecular and cellular microbiology, immunity and inflammation.

The year 2017 saw the confirmation of the role of Cryptosporidium in the development of digestive cancers and the development of a three-dimensional culture system for the colon to study the mechanism of carcinogenesis by C. parvum.

New methods have been developed for correlating photonic, electron and near-field microscopy.

Innovative approaches have led to the development of new classes of antibiotics against a very large number of bacteria, including those that are multidrug-resistant to conventional antibiotics.

Mechanisms dependent on mediators, epigenetics and cells linking environmental determinants and pathologies have been identified in the field of pulmonary diseases, and clinical studies in cohorts of patients have made it possible to evaluate the efficacy of new curative pulmonary treatments.

To build on the discovery of a new signalling pathway in chronic analgesia, a phenotypic screening of a chemical library on new cell models has identified new hits with analgesic potential.

Bacterial strains capable of limiting weight gain and improving metabolic disturbances related to obesity were selected, showing that the effect is multifactorial associating a restoration of the dysbiosis of the microbiota and an impact at the enteroendocrine and cerebral level.



In 2017, CIIL welcomed a new Chemical Biology of Flatworms (CBF) team led by Oleg Melnyk and focused on schistosomiasis, the second most widespread parasitic disease after malaria. It builds on its past successes in the development of innovative approaches in protein chemistry, in the study of signalling pathways and especially in the development of new therapeutic strategies in order to advance in the fundamental knowledge of Schistosoma mansoni and discover new antiparasitic approaches. The research focuses on the study of the development and fertility of the parasite. As a model, the team uses another flatworm, Macrostomum lignano, for genetic and functional studies that cannot currently be conducted in S. mansoni.

The team led by Dr Mathias Chamaillard highlighted the decisive role of the interaction between the internal clock and the commensal flora. It showed that an accumulation of bacteria whose abundance fluctuates according to the circadian rhythm correlates with alterations of the expression of many key players of the internal clock system. She demonstrated the importance of the composition of the intestinal flora on the anti-inflammatory and anti-proliferative properties of a chemical compound of the family of flavonoids widely present in fruits and vegetables.

A second team was created in 2017 by the merging of two teams working respectively on plasmodium falciparum and toxoplasma gondii. This team, led by Jamal Khalife, is studying the cellular and molecular biology of these two parasites. It aims to decipher the mechanisms implemented for their developments and differentiations. Their life cycle goes through different stages, which requires precise spatio-temporal control ranging from gene expression to the post-translational modifications of proteins and the regulation of vesicular trafficking and organelle biogenesis. The team discovered two ApiAP2 transcription factors, described the interactome of the protein Phosphatase 1 and discovered two new regulators of secretory organelle biogenesis.

The team led by Priscille Brodin identified a new signalling pathway for pulmonary epithelial cells, one of the first types of cells encountered by the tuberculosis bacillus at the time of infection, which allows them to reduce their colonisation by M. tuberculosis. It demonstrated that the activation of the M3R-ARF1-PLD1-ARFGAP1 pathway causes a modification of the actin cytoskeleton of the epithelial cell which restricts its colonisation by the bacillus. The team also discovered how the TB bacillus diverts the innate response of the macrophage to support its intracellular survival: the cellular protein CISH is positioned as a defender of the bacterium at the level of the phagosome by its ability to destroy the proton pump which is normally responsible for eliminating the bacillus.

A new research topic on the hepatitis E virus (HEV) was started in the team led by Jean Dubuisson. Research on this new topic has already led to several major advances in understanding the infectious cycle of the recently published in the Gastroenterology journal. The team demonstrated that during its infectious cycle, the virus produces 3 different forms of its capsid protein ORF2: one form called ORF2i, which is the form associated with infectious particles and two other forms called ORF2g and ORF2c, not associated with infectious materials and which are the major viral antigens present in the serum of patients infected with HEV. This work opens up new possibilities for the diagnosis of hepatitis E.

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The laboratory's mission is to design and synthesise drug prototypes with an innovative mode of action. This interdisciplinary molecular invention work is inspired by the most recent discoveries made on infectious diseases, metabolic diseases and cancer. This work proposes targets to aim in the body with new active compounds.

Drugs and Molecules for living systems

Pr Benoit DeprezPU - Lille University U1177 Inserm, Institut Pasteur de Lille, Lille University (Pharmacy faculty)

The design and optimisation of new drugs requires interdisciplinary expertise covering chemistry, physics, biology and in silico modelling. Indeed, the active ingredient of modern drugs, whether they are synthetic or biological in origin, is always defined at the molecular, or even the atomic, level. This particular

molecular structure - perfected by the researchers of the unit - is the key to all the properties of the drug. It conditions its ability to cross the physical and chemical barriers between the different biophases (intestine, blood tissues, brain, etc.) of the body and reach the intended target. It is also key to its interaction with the intended target and the achievement of the desired effect.

Beyond the therapeutic goal, molecules also serve as valuable tools that help biologists better understand how the cell and living organisms work and verify that the proposed targets for treating diseases are relevant.

Researchers are working on antibiotic resistance, type 2 diabetes, certain forms of cancer, the recognition of intracellular antigens by the immune system and pain.



Discovery of a new molecule to abolish the resistance to antibiotics of Mycobacterium tuberculosis, the infectious agent responsible for tuberculosis, in close collaboration with Alain Baulard's team on the campus and two pharmaceutical companies. This discovery is the culmination of several years of collaborative research, crowned by an article in the prestigious journal Science, and the decision to name the drug candidate for development by industrial partners.

Participation in the clinical study showing the influence of circadian rhythm on the postoperative consequences of cardiac surgery. In collaboration with the cardiologists and researchers from the unit led by Bart Staels, the team helped demonstrate that pharmacological intervention on the biological clock can be used to mitigate the risks associated with open-heart surgery. The ability to correlate the exposure of the heart to the time-adjusted pharmacological agent and gene expression was key in this study. These works were published in the prestigious journal The Lancet.

Published results of the pharmacokinetic study of a large class of molecules targeting many metalloproteins, with implications in infectious diseases, the control of gene expression (epigenetic) cardiovascular diseases and cancer. This study gives researchers the keys to optimise the stability of these molecules in vivo and demonstrates the interest of the pharmacokinetic and bioanalytical platform of the research unit. Results published in the American review, the Journal of Medicinal Chemistry.

The team has shown that it is possible to design a "signal" molecule that will help the body to assimilate the carbohydrates meal and reduce the post-prandial glycemic peak by targeting specific cells of the intestine. These innovative molecules showed activity in animals that had become prediabetic. Their development is funded by SATT Nord and the data was published in the international review, Journal of Medicinal Chemistry. This work was done in collaboration with Bart Staels' team.

In collaboration with Priscille Brodin, the team has developed a method of cell screening that has identified molecules that mimic the pain-relieving activity of mycolactone. These molecules are starting points for designing a new class of painkiller agents that are totally different from the opioid or anti-inflammatory agents currently used in clinical environments.

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The research unit on the genetics of diabetes and obesity was created at Institut Pasteur de Lille in 1995. It is made up of two teams: "human genetics" led by Prof Philippe Froguel and "animal modelling" led by the Dr Jean-Sébastien Annicotte. It includes 50 people – research professors and engineers. The UMR8199 is at the origin of the EGID laboratory of excellence (labex) and genomics equipment of excellence (equipex) LIGAN personalised medicine platform.

Integrated Genomics and metabolic diseases modeling

Pr Philippe Froguel University Professor-Hospital Practitioner (PU-PH in French) - Lille University - Lille University Hospital, LabEx UMR8199EGID, CNRS, Institut Pasteur de Lille, Lille University

2017, key year for the development of diabetes research in Lille: In June 2017, the UMR8199 relocated to its new EGID labex premises at the research centre of the Faculty of Medicine on the campus of the Lille University Hospital. The EGID building is the ideal place for developing the genomics

platform of the LIGAN equipex to serve medical research and patients suffering from genetic diseases or cancers.

The goal of EGID is to create the ideal conditions for "translational" research on diabetes that commands a global reputation and has a real positive impact on the lives of diabetics. The organization in two teams of the UMR8199 allows first the identification of new pathways leading to metabolic diseases, then the establishement of cellular or animal models in order to conduct

in-depth studies leading to the development of new diagnostic and therapeutic strategies. UMR8199 was the first team in the world to demonstrate the existence of monogenic forms of diabetes and obesity, and to explore the genome of diabetics and obese people in search of common genetic variants (genome-wide studies known as GWAS).

In 2017, UMR8199 used its unique DNA sequencing platform in France to find new genes for obesity, but also to better diagnose early-stage type-2 diabetes (T2D) of genetic origin which can ultimately be used in the personalised medicine of certain diabetes. UMR8199 also explored the sometimes mysterious function of genes involved in T2D opening up new ways of treatment. It also began an ambitious study, crowned with the ERC, on the regulatory regions of the genome of pancreatic cells, liver cells, adipose tissue and muscles, which are tissues that are essential in regulating blood sugar levels. Finally, it also conducted studies on the epigenetic effect (modifying gene activity) of the environment on metabolism, and on its consequences on the hepatic complications of T2D.



The diabetes genes discovered by the genome-wide studies (GWAS) decrease the secretion of insulin. The GWAS of the T2D gene identified many gene variants, but their role in pathophysiology was poorly understood. The team analysed the expression of the T2D genes in a panel of human tissues using an innovative technique for counting RNA molecules, and found that the T2D gene expression was enriched in β cells, assuming that it plays a key role in the secretion of insulin. Using cell biology, it has been demonstrated for the 1st time that there are 4 genes involved in the secretion of insulin. Then, the pathways impacted by the decrease in the expression of these genes was decrypted. This study made the cover of the Molecular Metabolism journal.

A new genetic mechanism for severe obesity. The team led the way in the late 90s with the discovery of the first childhood obesity genes, including the mutated MC4R receptor in 5% of obesity cases in France. To find new genes, the researchers assembled a cohort of inbred obese families from Pakistan studied using exome sequencing. Mutations of the ADCY3 enzyme in several Pakistani families have been identified. ADCY3 regulates the appetite but also plays an important role in controlling the activity of brown adipose tissue, which is important in energy expenditure in response to cold. This discovery published in Nature Genetics opens new therapeutic prospects against extreme obesity.

Multicentric Genetic Diagnosis MGSD.Monogenic diabetes (~2% of diabetic patients in northern Europe) is poorly documented in southern countries. In collaboration with the Mediterranean Diabetes Study Group (MGSD), the team performed exome sequencing from salivary samples in 250 diabetic patients before 40 years of age (multicentric study covering 9 countries and 35 centres). The current analysis for 2 centres (Malta and Greece) shows a genetic diagnosis rate of 40% and more than 60%. These genetic results will improve clinical monitoring and therapeutic adaptation according to the genetic cause. Beyond this, the challenges are to assess the geographical distribution of genetic sub-types, their prevalence by country, and the search for other specific etiologies.

The line of research on brown adipose tissue against diabetes. In a study published in the Molecular Metabolism journal, researchers showed, in mice, that the invalidation of the CDKN2A gene, which is a major regulator of the cell cycle, increases the expression of specific markers of brown fat cells from the abdominal adipose tissue. This causes generalised browning and improves adaptation to metabolic stress, with resistance to obesity induced by a fat-rich diet. These effects have been confirmed in human stem cells, whose CDKN2A gene has been invalidated, leading to their differentiation in brown adipose tissue. These results suggest that blocking this gene in humans may be a new opportunity for treating obesity and related diabetes.

ERC Starting Grant Reg-Seq (Amélie Bonnefond, 2017-2022). T2D is a complex disease that depends on the environment (age, sedentary lifestyle, etc.) with an important genetic component that remains today largely unresolved. Using a next generation DNA sequencing that has been implemented and developed since 2009 in the unit, researchers will decrypt the non-coding genome of several thousands of individuals. The team will focus particularly on the key DNA regions that regulate the expression of the active genes in the organs that are highly affected by T2D including the pancreatic islets, skeletal muscle, liver and adipose tissue. The project will try to discover new pathways involved in T2D, or even potential new treatment methods.

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Scientific research on cancer in the campus of the Institut Pasteur de Lille is conducted by six research teams.Since the discovery of the first cancer genes, the oncogenes, researchers have attempted to identify the molecular mechanisms through which a normal cell becomes tumoral and eventually metastatic. For five years, these teams have participated in a larger program at the Lille level, the integrated cancerology site in Lille, ONCOLille. This wall-less structure facilitates intense dialogue between clinical teams and fondamental research teams to identify new targets for cancer treatments. This is the case, for example, of molecular actors involved in tumoral angiogenesis (creation of vessels that irrigate the tumor) or in the bone metastasis of prostate cancer, as well as receptors on the cell surface (tyrosine kinase receptors) involved in lung cancers.

MecHanism of tumorigenesis and targeted therapies

Dr Yvan de Launoit Research director at CNRSUMR 8161, CNRS, Institut Pasteur de Lille, Lille University

The MET tyrosine kinase receptor and its ligand, the hepatocyte growth factor, are essential for embryonic development, while the deregulation of MET signalling is associated with tumorigenesis leading to various cancers, including lung cancer. Mutations in the kinase domain of MET lead to constitutive kinase activity and are associated with tumorigenesis. In lung cancer, however, some mutations are found in the juxtamembrane domain, and their functional consequences are unknown. David Tulasne's team has previously shown that the juxtamembrane domain of MET is targeted by several proteolytic cleavages, involved in its degradation during cell death for example. It is within this context that this team evaluated the influence of these mutations on the proteolytic cleavages of MET. Consequently, the mutation of MET on arginine 970 (R970C), promotes the generation of a fragment of 45 kDa not yet described (p45 MET). This fragment was also found in a lung cancer cell line carrying the R970C mutation. The team then showed that the proteases of the calpain family are responsible for this cleavage. In addition, the p45 MET fragment promotes the invasion of lung cancer cells. The targeting of these mutated forms of MET could be of interest in the current context of the development of targeted therapies in lung cancer.

MicroRNAs are the key regulators of angioge-nesis (vessel formation), as demonstrated by the vascular defects observed in animals with a deficiency in a specific microRNA, i.e. miR-126. Virginie Mattot,

in Fabrice Soncin's team was able to show that miR-126-5p is expressed in the cells of blood vessels, as well as in the neuronal cells of the retina. During the establishment of the retinal vasculature, she demonstrated that miR-126-5p participates in protecting endothelial cells from programmed cell death due to its activity in the neurons. The molecular mechanism associated with this phenotype is based on the miR-126-5p control of the expression of SetD5, a member of the methyltransferase family, which is involved in transcriptional regulation.This discovery could open up new therapeutic pathways in oncology, for example, where the vascular system plays a crucial role. Villain et al. miR-126-5p promotes retinal endothelial cell survival through SetD5 regulation in neurons. Development. 2018 Jan 8;145(1).

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The mRNAs carrying a premature stop codon are exported from the nucleus to the cytoplasm of the cell either to be degraded in the cell by a quality control mechanism called nonsense-mediated mRNA decay (NMD), or to be translated into a truncated or whole protein following the readthrough of the premature stop codon. Fabrice Lejeune's work with David Tulasne's team has shown that the cytoskeleton plays a major role in the fate of these mRNAs carrying premature STOP codons by transporting them either to cytoplasmic foci called P-bodies from where they will be degraded, either to a new type of cytoplasmic foci called Readthrough-bodies allowing the readthrough for the synthesis of a full-length protein. This is the first demonstration that the readthrough is very localised in the cell and distinct from the classical translation of mRNAs into proteins. These results provide a better understanding of the mechanisms targeted in the development of therapeutic methods for tackling rare diseases or forms of cancer caused by nonsense mutations.Jia et al., Premature termination codon readthrough in human cells occurs in novel cytoplasmic foci and requires UPF proteins. J Cell Sci. 2017;130(18): 3009-3022.

Senescence is a cellular state acquired in response to various stresses that occurs when the unfolded protein response (UPR) pathway is activated. However, the UPR targets which might relay the establishment of the senescent phenotype are not known Olivier Pluquet, in the team of Corinne Abbadie, showed that the inducers of the UPR cause premature senescence by an increase in the expression of the enzyme COX2, and an overproduction of prostaglandin E2 (PGE2) in wild-type fibroblasts, but not in those that are inactivated for the transcription factor ATF6α (a branch of the UPR). In replicative senescent fibroblasts, the inactivation of ATF6α prevents the induction of COX2 and PGE2 production. They then observed that the expansion of the endoplasmic reticulum as well as the spreading of the cells, characteristic of senescent fibroblasts, was greatly reduced during the invalidation of COX2 or ATF6α. These results support a critical role for ATF6α in establishing and maintaining cellular senescence in normal human fibroblasts by upregulating a COX2/PGE2 pathway. These results should ultimately lead to the identification of new molecules, targeting the components of the ATF6α branch, with potential anti-ageing and anti-cancer effects (by limiting the production of an inflammatory secretome associated with senescence).Cormenier et al., The ATF6α arm of the Unfolded Protein Response mediates replicative senescence in human fibroblasts through a COX2/prostaglandin E2 intracrine pathway. Mech Ageing Dev. 2017 S0047-6374(17)30077-5.

Bone metastasis is the major deleterious event in prostate cancer. The genomic fusion of TMPRSS2-ERG is one of the most common chromosomal rearrangements in prostate cancer. However, its involvement in the development of bone metastases is not established. Knowing that bone metastases start with the tropism of cancerous cells, towards the bone, by specific migratory and invasive processes involving osteomimetic capabilities, it is crucial to better understand the influence of TMPRSS2-ERG expression in the mechanisms underlying bone tropism of prostate cancer cells. Martine Duterque-Coquillaud's team has developed bioluminescent cell lines expressing the TMPRSS2-ERG fusion in order to evaluate its role in tumour growth and the appearance of bone metastases in a mouse model. It has shown that TMPRSS2-ERG fusion increases cell migration in vitro and the size of the subcutaneous tumour in vivo. But above all, thanks to in vivo experiments, it has shown that the expression of TMPRSS2-ERG fusion increases the number of metastases in the bone. In addition, TMPRSS2-ERG affects the metastatic spread profile by increasing the incidence of tumours in the hind limbs and spine, which are the most common sites of prostate cancer metastasis in humans. Finally, transcriptome analysis identified a series of genes regulated by fusion and involved in the metastatic process. This work indicates that TMPRSS2-ERG increases the bone tropism of tumour cells and the development of the metastases of prostate cancer.Deplus et al., TMPRSS2-ERG fusion promotes prostate cancer metastases in bone. Oncotarget. 2017; 8(7): 11827-11840.



u1011

Research teams on the campus

Director: Bart Staels

nucLeAr receptors, cArdiovAscuLAr diseAses And diABetesInserm - Lille University - Institut Pasteur de Lille

Team 1: Nuclear receptors in the metabolic syndrome / Manager: Bart StaelsTeam 2: Molecular control of monocyte / macrophage functions in the cardiometabolic syndrome Manager Sophie Susen / Eric Van BelleTeam 3: Nuclear receptors, immuno-inflammation and cardiometabolic pathologies Manager: David DombrowiczTeam 4: Molecular analysis of gene regulation in the cardiometabolic syndrome Manager: Philippe Lefebvre

u1167 Director: Philippe Amouyel

risK fActors And moLecuLAr pAthwAys of Aging-reLAted diseAsesInserm - Lille University - Institut Pasteur de Lille

Team 1: Public health and molecular epidemiology of cardiovascular diseases Manager: Philippe AmouyelTeam 2: Molecular determinants of heart failure and ventricular remodelling Manager: Florence PinetTeam 3: Molecular determinants of Alzheimer's disease and cognitive disorders Manager: Jean-Charles Lambert

u1177 Director: Benoît Déprez

m2sv: drugs And moLecuLes for Living systems Inserm - Lille University - Institut Pasteur de Lille

umr8199 Director: Philippe Froguel

integrAted genomics And metABoLic diseAses modeLingCNRS - Lille University - Institut Pasteur de Lille

Team 1: Genomics and epigenomics of metabolic diseases / Manager: Philippe FroguelTeam 2: Molecular bases and modelling of diabetes and obesity / Manager: Jean-Sébastien AnnicotteSC: Joint Research Department / Manager: Jérôme Delplanque



u1019 - umr8204 Director: Camille Locht

center of infection And immunity of LiLLeInserm - CNRS - Lille University - Institut Pasteur de Lille

Team 1: Biology and Chemistry of Platyhelminths / Manager: Oleg MelnykTeam 2: Biology of Apicomlexa parasites: factors regulating growth, differentiation and virulence Manager: Jamal KhalifeTeam 3: Biology and Diversity of Emerging Eukaryotic Pathogens (BDPEE) / Manager: Eric ViscogliosiTeam 4: Basic and clinical immunology of parasitic diseases / Manager: Sylviane PiedTeam 5: Molecular and cellular virology / Manager: Jean DubuissonTeam 6: Plague and Yersinia pestis / Manager: Florent SebbaneTeam 7: Chemogenomics of Intracellular Mycobacteria / Manager: Priscille BrodinTeam 8: Bacterial respiratory infections: Pertussis and Tuberculosis / Manager: Camille LochtTeam 9: Microbiology and cellular physics of infection / Manager: Frank LafontTeam 10: Lactic bacteria and mucosal immunity / Manager: Corinne GrangetteTeam 11: NODS-like receptors in infection and immunity / Manager: Mathias ChamaillardTeam 12: Pulmonary Infection and Innate Immunity / Manager: François TrotteinTeam 13: Pulmonary immunity / Manager: Anne TsicopoulosEEH: Chemical Biology of Antibiotics / Manager: Ruben HartkoornSC: Common service and scientific management / Manager: Zarifé Hanna-AbboudPlatform: Laboratory of applied transcriptomics and genomics studies / Manager: David HotPlateform: BICeL / Manager: Frank LafontPlateform: P3M / Manager: Jean-Michel SaliouPlateform: ARIADNE / Manager: Priscille BrodinPlateform: EPLS / Manager: Gilles Riveau

umr8161 Director: Yvan de Launoit

MechanisMs of tuMoRigenesis and taRgeted theRaPiesCNRS - Lille University - Institut Pasteur de Lille

Team 1: Initiation of epithelial cancers (ICE) / Manager: Corinne AbbadieTeam 2: Functional studies of the H1C1 tumour suppressor gene (H1C1) / Manager: Dominique LeprinceTeam 3: Activation of angiogenesis endothelium and cancer / Manager: Fabrice SoncinTeam 4: Signalling, apoptosis and cancer (SIGNAL) / Manager: David TulasneTeam 5: Immunoregulation of virus-induced cancers / Manager: Nadira DelhemTeam 6: Protein and related diseases / Manager: Martine DuterqueUMS 3702: Joint service unit Lille Institute of Biology (general secretariat of the IBL and of the IBL) Director: Philippe Boutin



Technology platformsimAging - tissue And ceLL-cytometry

U1177, Inserm U1019, UMR 8204, Inserm, CNRS, Institut Pasteur de Lille, Lille University

Manager: Frank LafontThe BioImaging Center Lille-Nord de France (BICeL), represents the most

important part of EquipEx ImaginEx BioMed.Website: www.bicel.org

trAnscriptomics And AppLied genomics

trAnscriptomics And AppLied genomics group (tAg) U1019, UMR8204, Inserm, CNRS, Institut Pasteur de LilleManager: David HotHigh-throughput genomics platform specialized in microbial genomics. Since 2012, TAG has been a member of the Genes Diffusion Genomic Platform for the implementation of a common structure called PEGASE, in order to offer cooperation and services pooling the skills of each of the entities.

peptide chemistry

peptide chemistry, systems, BioLogy UMR 8161, CNRS, Institut Pasteur de Lille, Lille University

Manager: Oleg MelnykPeptide chemistry and protein chemical synthesis

Website: www.csb.cnrs.fr

high-throughput screening (hts) And high content screening (hcs)U1177, Inserm, Institut Pasteur de Lille, Lille UniversityManager: Benoit DeprezPlatform that combines a chemical library and all the high-throughput screening tools (except for the techniques based on high-throughput confocal imaging which are available on the microscopic imaging platform).Website: www.deprezlab.fr

hts & phArmAcocinetics Adme-pK screening LAB

U1177, Inserm, Institut Pasteur de Lille, Lille UniversityManager: Benoit Deprez

Platform allowing for the qualitative and quantitative characterization of the prospects of experimental active ingredients when tested on animals.

Website: www.deprezlab.fr



nucLeAr mAgnetic resonAnce

nucLeAr mAgnetic resonAnce UMR8576, CNRS, Institut Pasteur de Lille, Lille UniversityManager: Guy LippensNuclear magnetic resonance (NMR) spectroscopy helps probe the molecular structure by making the natural magnetization of nuclei interact with a magnetic field.

pLehtA pLAtform

Institut Pasteur de LilleManagers: Jean-Pierre De Cavel and Fabrice Infanti

Laboratory for research and experimentationNSB3 high biological security laboratory for the secure handling of

infectious biological agents (viruses, bacteria, etc.) or others (toxins, etc.).

genome study LABorAtory

genomic AnALysis LABorAtory U1167, Inserm, Institut Pasteur de lille, Lille UniversityManagers: Philippe Amouyel and Nathalie Fievet-VerrecasLogistics and oversight of large collections of human biological samples with patients recruited mainly from epidemiological studies based on the cardiovascular, metabolic and neurodegenerative disease themes.

genomics And metABoLic diseAses

EquipEx LIGAND-PM (Lille Integrated Genomics Advanced Network for Personnalized Medicine)

Manager: Philippe FroguelThe Lille Ligan-PM platform for genome sequencing can establish the list of mutations likely to explain the clinical signs of each patient, predict the

possible evolution of his/her disease, and predict the efficacy or side-effects of existing drugs.

Website: http://ligan.good.cnrs.fr

proteomics And modified peptides pLAtform (p3m)LabEx ParaFrap, Institut Pasteur de Lille, CNRS, Lille UniversityManager: Jean-Michel SaliouPlatform dedicated to proteomic analysis and the characterisation of proteins and peptides.


All working together to drive progress in researchLeaving Healthier for longer time

For the last 120 years

All working together to drive progress in researchLeaving Healthier for longer time

For the last 120 years


BiotechsAt the heart of the campus, the Institut Pasteur de Lille supports the development of projects, start-ups and biotechnology and health innovation companies. The aim is to bring new services and analysis or diagnosis products which stem directly from the fundamental research carried out in Lille. The Institut Pasteur de Lille relies particularly on the proximity of its research teams and their equipment (laboratories and technological platforms) to facilitate collaboration with the entrepreneurs and start-ups of the sector, whether they be in the experimental or developmental phase. The Institute is also committed to fostering synergies and expertise in order to allow biotechs to move more easily into the maturation phase of their projects.These biotechs, located on the Pasteur Lille Campus, benefit from the available premises, equipment and skills.

Created on the campus of Pasteur Lille in January of 2001, Genoscreen offers analytical services in genomics on all types of genomes (human, animal, vegetable, microbial) and bio-computing analyses and training, both for "academic" research teams and for hospital or industrial research. This 100% French biotechnology company now has about thirty employees. 80% of its turnover is generated outside of Metropolitan Lille, of which 30% is exported. Over the past few years, research programs in themselves, conducted in partnership with research units from the Institut Pasteur de Lille, INSERM and the INRA have contributed to the development of some very competitive applications in areas such as the genetics of Alzheimer's disease, microbial molecular typing and monitoring of biodiversity.

www.genoscreen.fr

Set up on the Lille Pasteur campus, the company X'ProChem markets proteins synthesized using a chemical method, an innovative technology stemming directly from the academic research of the laboratory of Oleg Melnyck. These 100%

chemical proteins are custom-made to meet requirements that classic methods of recombinant biology are unable to synthesize, such as toxic, membrane proteins or proteins equipped with a probe so they may be traced in cellular imaging. The first papers published on protein chemical synthesis date back to the '30s, but we had to wait for the end of the first decade of this century before a cost-effective, easily replicable method was developed at the Institut Pasteur de Lille.

www.xprochem.com/fr

Strengthened by its collaborations with the Pasteur Lille campus, 4 P-Pharma develops innovative molecules at an early stage of pre-clinical development and brings them to the preliminary phases of clinical trials. The company is positioned

as an intermediary between entities that have developed high-potential early biomedical projects and the pharmaceutical companies. Since September of 2016, 4P-Pharma has also been financially supported by the mutual company "M comme Mutuelle" to conduct the first phase I clinical trial on one of its products possessing properties that constitute a deterrent to psycho-stimulant abuse.R&D's activities focus on inflammatory diseases, oncology and the central nervous system. Around ten drug candidates are currently being developed in the molecule portfolio. The ongoing projects of 4 P-Pharma have benefited from several collaborations with the teams of the Institut Pasteur de Lille, especially with the Pharmaco-kinetics/ADME platform directed by Prof. Benoit Deprez, the Transcriptomics and Applied Genomics platform directed by Dr. David Hot, and the Genetic Toxicology Laboratory directed by Dr. Fabrice Nesslany.

www.4p-pharma.com



In close collaboration with the research teams of the Pasteur Lille campus, Lunginnov develops and markets innovative solutions targeting respiratory diseases that facilitate earlier therapeutic decision-

making in the interest of the patient. Lunginnov is a platform for developing new theranostic concepts for respiratory diseases. The first biomarker has just received the approval of the Ministry of Health making it reimbursable (RIHNv2016). This biomarker was discovered at the Institut Pasteur de Lille in 1996 within the Lille-based academic respiratory research unit. It allows early diagnosis of the risk of respiratory complications before they occur, from the moment the patient is admitted to intensive care. The benefits of this biomarker stemming from modification of the intensive care patient's treatment include a positive impact on the incidence of ARDS and on overall mortality, as well as on the duration of ventilation or the length of time spent in resuscitation.Lunginnov offers a complete diagnostic solution with the provision of a dosing robot, maintenance, and manufacture of the fully internalized assay reagents validated by the ANSM (the national agency for drug and health product safety).Respiratory failure today costs society close to €370 million per year. The introduction of biomarkers developed by Lunginnov could lead to a 15% saving in health costs.In addition, a close collaboration between Inserm, Institut Pasteur de Lille and the CHU de Lille has been established in order to develop new diagnostic concepts and new pulmonary tropism biomolecules, two of which are already at the clinical stage. Lunginnov is a diagnostic company that incorporates a complete value chain from R&D to controlled manufacturing, and from the clinic to the sale.

www.lunginnov.com/fr

Created in 2013 by Terence Beghyn, pharmacist and researcher, along with Prof. Benoit Deprez, Director of the Drug Discovery Center of the Institut Pasteur de Lille, Apteeus is an innovative company in the field of individualized medicine for patients with rare and orphan diseases. Thanks to their expertise acquired in the U1177 Research Unit (Inserm - Institut Pasteur de Lille - Lille University), their mission is to bring the miniaturized techniques of drug discovery to the bedside of patients suffering from orphan diseases.

The APTEEUS approach combines in vitro cell screening with drug repositioning. The team's savoir-faire, with the assistance of doctors and scientific experts in disease, have made it possible to develop a screening test for any new disease sufficiently characterized from a functional point of view. The test systematically uses cells taken from the patient to guarantee the link between the molecular cause of the disease that is specific to the patient with its symptomatic manifestations. Thus the idea is to measure the effect of each of the active ingredients of the medications from the global materia medica on the altered function at the root of the symptoms. It is the exhaustiveness of the collection of active ingredients, the relevance of the tests developed, and the environment of scientific excellence that constitute the strengths of APTEEUS today.The company is currently evaluating the clinical benefit of two drug candidates in several rare and orphan pathologies. Drug repositioning is a means of quickly responding to the medical need of small populations of patients by mastering both the risks and costs of development.The patient's involvement in the discovery process earned APTEEUS the prize in the category of Individualized Medicine of the Concours Mondial d'Innovation. Today, several partnerships with teams from the Institut Pasteur de Lille, various hospitals and pharmacy actors, are making it possible to broaden the scope of the technology.

http://apteeus.fr

Led by the doctors Nadira Delhem and Olivier Moralès and directed by Hamza Aboussemdai, this biotech officially commenced in July of 2016 on the premises of the Lille Institut de Biologie (CNRS) on the campus of the Institut Pasteur de Lille. Immune InsighT offers an unprecedented and effective method of validating the safety of new drug candidates prior to the launch of clinical trials. A method directly stemming from Pasteurian research. It offers unique services internationally making it possible to validate, in a preclinical phase, the safety of a drug candidate with regard to immune cells, and T regulatory lymphocytes in particular. Balance of the immune system Regulatory T lymphocytes (Tregs) are a particular population of white blood cells that maintain the proper balance of the immune system so that it can protect the organism from aggression. Some diseases deregulate the function of the Tregs. Thus, in cancers, Tregs are abnormally activated, which weakens the immune response directed against the tumor and facilitates its progression. Conversely, in the case of allergies, chronic inflammatory diseases or organ transplants, the Tregs underfunction and the immune response is excessive.

www.immune-insight.com



LIVE BETTER TODAY IN ORDER TO AGE WELL TOMORROW



Prevention services - Health - Longevity

The disease prevention centre is built on the foundations and expertise of major services provided in the past by Institut Pasteur de Lille:

This development makes it possible to work with greater synergy, while reacting more quickly and making use of the pooled resources of the different trades, doctors, nurses, dieticians, administrative staff as well as the cross-departmental services.

In addition to the CPAM (Franch Health Insurance system) health checks and those for expatriates, the vaccination service for travellers, health education, clinical studies and training, the institute is strengthening its strategic positioning on Longevity throughout the new organisation.

In partnership with the Lille University Hospital and the Lille University, actions conducted by the Centre for Health and Longevity are conducted on the basis of the following 3 major objectives:

Institut Pasteur de Lille finances the management structure, the teams, the work and the equipment required for the Longevity assessments.

The Lille University Hospital and the Lille University contribute their expertise through a medical director (University professor and hospital practitioner), geriatrician and biologist specialising in ageing, a hospital practitioner in public health in charge of epidemiological research, a geriatrician-hospital practitioner in charge of the Longevity course, as well as junior doctors (residential and non-residential).

Partners such as the Regional Health Agency (ARS), AG2R La Mondiale or even Carsat Nord-Picardie, support this innovative project for its development at the national level. In fact, complementary to the CPAM review, the Longevity Course was designed to be expanded across the country to offer a global health offer for the entire population, based on existing health networks.

The former Centre for Prevention and Health Education (Health Checks of the CPAM and the WHO Vaccination Centre)

The nutrition Department

The Education Department

15 132heaLth check-uPs

cPaMincluding 8,575 people in vulnerable situations

26,000 vaccines (including 6,000 anti-influenzavaccines) for 17,000 consuLtations

6,000caLLs Receivedby the vaccination dePaRtMent

LONGEVITY COURSE: longevity review,

personalised coaching and evaluation

TRAINING AND EDUCATIONIN HEALTH

PUBLIC HEALTH EPIDEMIOLOGICAL RESEARCH



Health check-ups and health workshopsIn 2017, 15,132 targeted health reviews were conducted in the health examination centres of Lille and Tourcoing as well as at sites outside the region in Lens, Arras and Boulogne. Their implementation was completed as part of the agreements with the CPAMs of Lille-Douai, Artois, Flanders, Roubaix Tourcoing and the Opal Coast. The health insurance system assigns these medical checkups more specifically to the more vulnerable people (people who are socially vulnerable, living alone, people who benefit little or not at all from the preventive measures offered by GPs, people who do not benefit from organised monitoring systems, screening and vaccination, etc…). In 2017, these so-called vulnerable populations represented more than 56% (50% in 2016) of the centres' patients. This figure that is on the rise is an indicator of the objective (50%), which has largely been met. In half a day, a series of medical tests is carried out (blood, auditory, cardiological, dietary, etc.) by the doctors and nurses of the health examination centre. Risk factors and healthy behavior are also addressed with dieticians and medical-sports educators.

Various directions are subsequently proposed:

4 Therapeutic education course for people with type II diabetes.

4 Workshops on the themes of food, physical activity and oral-dental issues.

The results of the check-up are then sent to the GP.

either towards workshops

or towards the structures of external partners.

1

2

The Disease Prevention Centre aims to develop a range of check-ups, especially for large companies. The bespoke assessment can therefore, by definition, be modulated according to requirements. Check-ups assessments in the frame of expatriation performed may be offered in connection with the International Vaccination Service.

The Longevity Course is the result of a reflection initiated in 2017 to propose an active approach to disease prevention in healthcare, that complements the CPAM assessments and which acts as an incentive to take real action in favour of one's health. This original and innovative course can be broken down into a number of steps:

4 a comprehensive self-administered questionnaire that can be completed at home (more than 350 questions)

4 a health check-up which looks back over the life time of the patient and defines their health profile 4 personalised coaching focused on education in ageing well, addictology, nutrition, physical,

cognitive and social activity, stress, memory, sleep, etc. 4 an assessment shared with the coach to measure the impact of this course on one's health

This longevity journey will focus on the keys to disease prevention in order to age healthily. It is based on the two major handicaps of ageing, i.e. cognitive and motor disorders. The high-risk factors, situations and behaviour of poor ageing and the occurrence of chronic diseases made it possible to define all the specific stages of the assessment. This Longevity course will be rolled out across the nation through partnerships and through the existing health networks. The 1st assessments will be conducted at Institut Pasteur de Lille in the 2nd quarter of 2018.

Check-ups assessments

The longevity course



4 18 regions in the 5 départements of the Hauts-de-France benefited from the initiative4 161 professionals from 82 social-care centres benefited from bespoke educational support4 468 users benefited from "self assessment educational course in global health and nutritional

behaviour workshops" type initiatives

4 4 agglomerations participated in the project in 6 regions for 40 local structures4 60 local players benefited from the initiative

As part of the city contracts of the Métropole Européenne de Lille, Institut Pasteur de Lille has forged a partnership with the City of Lille with the objective of running initiatives to improve well-being through adapted physical activity in order to reduce mental suffering in high-priority neighbourhoods.

4 2 neighbourhoods participated in the programme (Wazemmes and Moulins)

4 28 professionals were mobilised4 47 inhabitants benefited from the support

Guidance and skills development of support operatorson the theme of "nutrition-combating a sedentary lifestyle" for 8 days with the following results:

Awareness building session on nutrition and combatingsedentary lifestyles of local players in 4 agglomerationcommunities:

Health and well-being educationIn 2017, the Well-Being Health Department actively participated in the overall health policy of the institute. The training and bespoke support in health education is one of the department's dominant activities. It works on the SOPHIA programme training courses for nurses responsible for monitoring diabetic policyholders.

Its nutrition expertise is recognised by the Technical Centre for Support and Training of the Health Examination Centres (CETAF in French). In this regard, the sports medicine educators and dieticians train the professionals of these health examination centres on national programmes aimed at the consultants targeted during the Health Check-Up (EPS in French) on issues dealing with diet and the lack of physical activity.

Two major regional initiatives were conducted in 2017 in collaboration with the Nutrition Department:

1

2

It is also recognised as a support operator by the Regional Agency of Hauts-de-France specifically in its area of expertise of "Nutrition, combining diet and physical activity", the fight against a sedentary lifestyle and vaccination. Its objective at a regional level: helping to increase the skills of those involved in disease prevention so that they can work independently to run projects addressing nutrition and vaccination.


Research and trainingInstitut Pasteur de Lille aims to share knowledge and train the specialists of tomorrow. This is why one of the major responsibilities is the support given to students, scientists and engineers, during long university courses (Master's research and PhD degrees) or short university courses (University degree (DU) and vocational degree). Each year, Institut Pasteur de Lille also develops more than 600 people – researchers and health professionals – in various fields of activity.

The Institute also trains specialists in:

4 Research activities in epidemiology/public health are under construction. The Longevity Course must be associated with a strong research activity related to preventive medicine. The research activity will be carried out using data collected in the Centre for Health and Longevity (in accordance with applicable legislation) but also in collaboration with the other research units of Institut Pasteur de Lille, the region, France and abroad.

4 The courses offered by Institut Pasteur de Lille have been enhanced with the launch of the "Longevity" University Diploma (Faculty of Medicine of Lille-IPL) in October 2017, run by Prof Patrick Berche and Prof Eric Boulanger. The "Biology of Ageing Process" Master's research degree (Paris 5-7, Tours, Versailles, Toulouse and Lille) opened a new module during the current year (2017-2018): "Extracellular Matrices, Cancer, Prevention, Longevity". The lessons were taught at the institute in November 2017. This year group chose the name of "Promotion Calmette" in honour of the man and in thanks to Institut Pasteur de Lille.

4 Finally, every year, the Nutrition Department also offers training which deal with the following themes: health and nutrition, education and a balanced diet, and nutrition for children, seniors and people with disabilities. In particular, this year, it ran training courses on the nutrition of disabled people in vocational rehabilitation centres (ESAT in French) and residential care homes, as well as training courses on food for children in inter-hospital childcare centres.

Good laboratory practices

Nutrition - diet Biological safety Addictive behaviour

Mutagenesis-genotoxicity Scientific tools

For several years now, the national plan has been to modulate the examinations offered to the consultants according to their gender, age, history, etc. These Disease Preventive Check-Ups (so-called CPAM assessments) are being put in place at the same time as the deployment of the renovated SAGE.2 software. All the teams are being trained to implement this important move forward.

The renovated check-ups assessments



The Nutrition Department conducts food education actions in public health. It acts on behalf of private and public actors and participates fully in the regional implementation of public policies in the field of food and health.

Public Health division This year, the Public Health Division of the Nutrition Service has conducted:

4 The PREV'HODE programme (Nutritional support for employees working shifts) aims to evaluate the impact of shift work conditions of these employees on dietary habits on the one hand and to improve their eating habits on the other hand.

How? By emphasising the pleasure of eating with a large number and a wide range of initiatives (food workshops, physical activity workshops, free fruit baskets, PR events, etc.)

4 AG2R La Mondiale: organisation of cookery course workshops for different groups of people (seniors, people suffering from Alzheimer's disease, people with cancer) to help them discover recipes and provide them with practical and bespoke nutritional advice.

4 other foundations:

• the 4th nutritional education programme based on the "Nutrissimo Junior" game introduced in schools for school staff and children thanks to the support of the following 5 foundations: The Fondation PiLeje, the Fondation Bel, the Fondation Auchan pour la Jeunesse, the Fondation Goût du Partage and Institut Pasteur de Lille.

• The organisation of the 6th conference on disease prevention "For a disease prevention policy for the youth" with the PiLeje Foundation at the National Assembly in November 2017.

4 the Thermal Baths de Brides-les-Bains:

• The Nutrition Department also organised the 9th nutrition and hydrotherapy workshops on fibromyalgia in Allevard les Bains.

Nutrition

a research-action project in partnership with Citéoand the Occupational Health Centre and with the support of the FFAS (French Food and Health Fund):

field-based projects in partnership with:

Auchan Retail France has made a commitment to work alongside Institut Pasteur de Lille to live better, in better health.

Indeed, the Nutrition Department has been providing its expertise to Auchan Retail France since the beginning of 2016, particularly as part of the Good Food programme, which aims to guide consumers towards better food choices with a tailored offer and support for improving dietary habits.As a result, the institute's nutrition department has developed simple and practical nutritional information packages, which are available to customers in the stores. Auchan employees have also been trained to lead educational workshops on the subject of Good Food.Auchan Retail France has ramped up its commitment through corporate sponsorship.

Partnership with Auchan

The expertiseThe Nutrition Department continues its specialist consulting and assistance activities for Primevère, Lesaffre, Leroux, Alliance 7, Thermes de Brides-les-Bains, Auchan, etc.



New version of Nutrissimo Junior®

The Nutrissimo Junior® game, a tool for building awareness among the youth about good nutrition, created by the Nutrition Department of Institut Pasteur de Lille, has been completely revised. This brand new version of this informative game is marketed in Auchan stores and available from Institut Pasteur de Lille.

Clinical studies

For 15 years, the Nutrition Department has been assisting numerous food sector industrialists (ingredients, food, food supplements) in evaluating the health benefits of their products. It has thus gained strong expertise in the management of clinical nutrition studies.

So, the Nutrition Department, and its NutrInvest clinical Investigation center, managed five clinical nutrition studies in 2017:

which evaluates the effect of a dietary supplement consisting of a probiotic yeast on LDL cholesterol levels in volunteers with moderate hypercholesterolemia.

THE HONEY STUDY

, which focuses on the effect of a new nutritional solution (containing a symbiotic) on intestinal permeability, and the comfort and quality of life of volunteers with celiac disease.

THE PROTALSAFE STUDY

, which aims to analyse the effect of the consumption of a first-age infant formula on infant growth from 0 to 6 months.

THE BABY MILK STUDY

that studies the effect of a probiotic yeast on improvements in gastrointestinal disorders associated with irritable bowel syndrome with predominant constipation.

THE IBS-GO STUDY

that determines the effect of a food supplement based on a mixture of plant extracts on carbohydrate and lipid homeostasis in people with Type 2 diabetes or a glucose intolerance associated with hypertriglyceridemia.

THE TOTUM-63 STUDY

The Nutrition Department also completed the Educatherm study started in 2013 on the evaluation of a therapeutic education course, in addition to a spa treatment, for overweight patients at the Thermal Baths of Brides-les-Bains.

THE EDUCATHERM STUDY



Several studies have been published in scientific journals, including a study on the under-nutrition of the elderly.In addition, thanks to the partnership between Institut Pasteur de Lille and the Eurabio laboratories, the Nutrition Department has put in place an active process for recruiting the volunteers participating in Nutrition clinical trials.On the institute's website, a page is devoted to the enrolment of volunteers in clinical studies: nutrition.pasteur-lille.fr

10 March 2017: renewal of the ISO 9001 certification

of the Clinical Studies centre

Event days on targeted topics (obesity, disability, Alzheimer's, etc.) and symposiums (nutrition talks, nutrition workshops) are also organized every year on the campus of the Institut Pasteur de Lille:

THE 19TH NUTRITION MEETINGS

- 15 AND 16 JUNE 2017 -• Dietary excesses on the programme• Animal/plant-life:

the keys to the debate

THE 16TH NUTRITION WORKSHOPS

- 7 DECEMBER 2017 -• Vulnerability, under-nutrition

and sarcopenia in the elderly

other highLights



UNDERSTANDING THE IMPACT OF POLLUTION ON HEALTH AND QUALITY OF LIFE



In Europe, it is estimated that atmospheric pollution causes 600,000 deaths a year (482,000 for outdoor air and 117,200 for indoor air). In France, the fine particle pollution from human activities would be the cause of at least 48,000 premature deaths each year, which is equivalent to 9% of mortality in France and a decrease in life expectancy at 30 years, which can exceed 2 years. The Hauts-de-France region bemoans the

worst health indicators in our country, with the highest mortality before the age of 60 and the highest rates of cancer, Alzheimer's disease, cardiovascular accidents, asthma, chronic bronchitis, diabetes and obesity, chronic inflammatory diseases of the digestive tract, etc. The Hauts-de-France is particularly exposed to atmospheric pollution because of the density of the population, increasing urbanisation, road traffic, industrial activity and agriculture. According to a 2015 regional review published by the Métropole Européenne de Lille, on the 4 Lens-Douai, Lille, Maubeuge and Valenciennes agglomerations, each year, air pollution would cause about 750 non-accidental deaths and 320 hospitalisations for respiratory and cardiac reasons. Recent works directly point to chronic exposure to air pollution as the cause of certain pathologies (diabetes, Alzheimer's disease, cancer, etc.)

For years, Institut Pasteur de Lille has been engaged in studies on this issue, particularly through certain research teams from the Lille Infection and Immunity Centre, the genotoxicity laboratory and the microbiological safety laboratory. In the Hauts-de-France region, many teams from very different backgrounds have long been involved in studies on environmental pollution. This work involves epidemiologists, doctors, researchers, immunologists, chemists, physicists, engineers, climatologists, etc.

Institut Pasteur de Lille decided to bring together all the regional teams working on pollution during a foundational conference on 6 November 2017 at the Pasteur-Lille campus. Each team presented its areas of interest and know-how in the field of environmental pollution. At the end of the conference, the decision was taken to create a Regional Pollution Health Longevity Centre coordinated by Institut Pasteur de Lille, with a joint management organisation (Dr Fabrice Nesslany - Institut Pasteur de Lille, Prof Damien Cuny - Lille University). The aim is to get the research teams of the region to interact by initiating multi-disciplinary cooperation on the impact of pollution on health and ageing.

This centre will bring together teams from the Universities of Lille, Picardie and Littoral Côte d'Opale (ULCO), the Lille University Hospital and the Ecole Nationale Superieure Mines-Télécom Lille-Douai (IMT Lille Douai). This centre is combined with an association committed to the prevention of air pollution (APPA).

The objective is twofold:

• mobilise resources and coordinate multi-disciplinary research with funding organisations (ANR, ARS, Region, I-site, EEC, etc.) It was decided to focus first and foremost on air pollution. Afterwards, other major issues will be addressed, such as the effect of endocrine disruptors and nanoparticles. Conferences will be organised with the consortium's teams.

• provide information and alert the general public to the issues of pollution and the diseases that they cancause, build awareness among decision-makers in order to combat pollution effectively.

Pollution Health Longevity Centre



The Laboratory of Genetic Toxicology carries out mutagenesis studies to highlight different types of genetic events leading to genotoxicity (genetic mutations, chromosomal aberrations and primary DNA lesions), toxicity studies in vitro (phototoxicity, corrosion, irritation on reconstructed human skin models), and assays for endocrine disruption activities through interaction mechanisms with estrogen and androgen receptors or steroidogenesis disruption.

Genetic toxicologyDr Fabrice Nesslany Research director of Institut Pasteur de Lille

The Laboratory of Genetic Toxicology is part of the university welcoming team EA 4483 (IMPECS – Impact of the Chemical Environment on Health) which aims to develop strategies

for assessing the exposure, impregnation and health effects of xenobiotics in humans, and to identify the molecular and cellular mechanisms involved in their pathogenicity

The Laboratory of Genetic Toxicology participates in many research programmes aimed at evaluating the genotoxic potential of nanoparticles, heavy metals, mycotoxins, e-cigarette liquids, etc.

The project for the years can be broken down into the following 3 objectives:

• "Health and environmental risks of nanoparticles and nanotechnologies"

• "Food safety"

• "Atmospheric pollution" with the development of the Regional Centre for "Pollution, Health, Longevity". The main objective of the centre is to gain an understanding of this topic and bring together all the research teams working on the topic.

In 2017, publication of 7 scientific articles in international peer-reviewed journals including the one published in Plos One corresponding to a study that demonstrated that nanoparticle vectorisation (PLGA) reduces the toxicity of domestic pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) after adsorption and does not potentiate the genotoxic effects. Carpentier R, Platel A, Maiz-Gregores H, Nesslany F and Betbeder D. Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants. PLoS One. 2017 Aug 15;12(8):e0183243.

Development of a high-throughput screening method to simultaneously evaluate markers of genotoxicity, aneuploidy, mutagenesis and cytotoxicity on cell cultures.

Development of an experimental model based on in vitro Bhas 42 Cell Transformation, to predict in vitro carcinogenic potential.

HIGHLIGHTS


The Microbiological Safety Unit (MSU) examines the behavior of pathogenic micro-organisms in the environment, and in particular, the response of micro-organisms to the means of control used to combat them. The Unit gathers together a set of skills and organisations specialised in managing infectious risks in the following fields: water, air, surfaces, cosmetics, health products, hospital environments.

Microbiological safety unit

Dr Michèle VialetteHead of unit Institut Pasteur de Lille

The axis of research revolve around the study of the response of different microbial species (Bacteria

or viruses) to the conditions or their environment whether natural or connected to human activities. The contribution of knowledge on the impact of a type of environment on the spread or destruction of micro-organisms has proven to be a major asset in the management of microbiological risks. The objective consists in evaluating and controlling the risks associated with the milieux, such as indoor air or hospital environments (combating hospital-acquired infections).

The team's expertise is nationally renowned for the study of bacteria and viruses that are highly pathogenic to human beings. Dr. Michèle Vialette is a microbiology expert for Anses (the national agency for food, environmental and occupational health & safety), serving on the committee of experts specialized in water.

The MSU also conducts specific studies for several industries in which there is some awareness of the management of contamination, such as the hospital sector or the cosmetics industry. Very involved with health actors, whether they be industrial, or hospital in nature or public authorities, the MSU contributes to the creation of tools for the control of environmental contamination.

HIGHLIGHTSThe treatment of infectious diseases of bacterial origin generally involves the use of antibiotics. In response to antibiotic selection pressure, bacteria have developed many mechanisms that make them more resistant, as well as the ability for genetic exchange with other bacteria. The MSU has therefore undertaken to develop a technological unit bringing together various multi-resistant micro-organisms (bacteria or fungi). In addition to the creation of a bank of resistant strains, that can be used to propose an offer of innovative expertise on field strains, the Unit's project is to implement studies comparing the behaviour of these strains to that of strains that are non-resistant to antibiotics with respect to environmental disinfection processes.

In 2017, MSU launched a partnership with Dyson France. A study on a humidifier developed by Dyson was used by MSU to demonstrate that this device eliminated 99.9% of the Legionella bacteria likely to be present in the water used to humidify the air. Consequently, these results are included in Dyson France's claims with the words "Tested by Institut Pasteur de Lille". This partnership will continue on new products.

MSU is a partner in a Franco-Belgian project that aims to finalise and market textiles with antiviral activity by contact. Such products are designed to reduce the transmission of pathogenic viruses by textiles, particularly in hospitals, in order to help combat hospital-acquired infections. Previous work has made it possible to identify a combination of molecules with anti-viral properties in the laboratory after grafting on various textile materials. In order to obtain a mature product that is adapted to the market, the work focuses on optimising the virucidal formulation and functional features on textiles, before validating the activity of the functionalised textiles used in hospitals.

In 2017, the USM signed a review article on the survival of viruses in water, published in the Intervirology journal. Pinon A., and Vialette M. 2018. Survival of viruses in water. Intervirology. DOI: 10.1159/000484899.

In 2017, the MSU signed a collaboration agreement with 4P Pharma. This R&D company aims to help develop innovative therapeutic solutions coming from breakthroughs in research. The agreement covers the studies and projects conducted in the laboratory testing sector on new antimicrobial products.



SUPPORT A MAJOR PROJECT ON LONGEVITY



Fund raisingContribute to major breakthroughs in diseases that prevent people from ageing wellThe Institut Pasteur de Lille is an independent private state-recognised public-interest foundation. Its ongoing existence for more than a century is therefore due to it generous donors and even today, it must raise three-quarters of its funding. Each contribution allows the institute to constantly reinvent itself in order to address health issues in greater detail and preserve its independence, freedom in research matters and ability to react quickly to change.In 2017, the funding operations (donations and bequests) raised € 3.3 million to speed up discoveries that will save millions of lives.

HOW TO LIVE BETTER FOR LONGER

Publication of 3 issues in February, April and October 2017.

19 FUNDRAISING CAMPAIGNS

To support work on cancer, Alzheimer's disease, diabetes and the discovery of new drugs.

113TH CONGRESS OF NOTARIES IN LILLE

Institut Pasteur de Lille participated in the French Congress of Notaries in Lille, in order to publicise the research objectives of the foundation.

A BROCHURE TO GUIDE THE THOUGHT PROCESS ON LEGACIES

THE FUNDRAISING PROCESS IS GOING DIGITAL!

With the creation of 3 digital events: ISF, Diabetes, Alzheimer's disease, an increase in the institute's presence on social networks and the end-of-year digital campaign: #tousunpeuchercheur ("everyone is a researcher")

ALL TOGETHER: FROM THE YOUNGEST TO THE MOST ATHLETIC

• SOLID’AIR with Weembi: two-day event in a free-fall simulator in favour of Institut Pasteur de Lille

• 3 open-day operations " At the heart of the labs "

• "Wednesdays at the museum"• Solidarity events• Online fundraising of committed

private individuals• Kid Campus: 15 classes of year-6 pupils

received by the researchers for one day

Contacts – donations and bequests: Sylvie Frémaux and Eugénie Devendeville+33 (0)3 20 87 72 06 - [email protected]



Business patronage

Auchan Retail France is committed

to living more healthily

by supporting the "Live

Better Longer" project.

An active collaboration

with the institute's

teams for good nutrition.

To ensure that Institut Pasteur de Lille can continue to be an evermore innovative centre for research and innovation, private funds must be raised. In 2017, the patronage provided by businesses contributed € 1.4m.

Verspieren provided financial support for the "Live better today to age well tomorrow" research programme of Institut Pasteur de Lille. The partnership signed in early December between Didier Bonneau, deputy managing director of Institut Pasteur de Lille, and Johan Cailliez, administrative and financial director of Verspieren, is binding until 2021.

Two personalities, Franck Thilliez, writer

and Jean-Claude Casadesus, conductor,

as sponsors, are raising appeals on behalf of

Institut Pasteur de Lille.

The campaign committee crea-ted a circle called the "Friends of the Foundation". They promote projects, participate in the life of the institute, and have an elected member and permanent guests on the Board of Directors.

the friends of the foundAtion

the memBers of the cAmpAign committeeVincent Behague (Adix)Patrick Lequint (KPMG)Thierry Letartre (ANIOS)Thierry Mathieu (Eurabio)Laurent Roquette (Floriscope)André Tordeux (Genoscreen)Patrick Vacossin Brigitte Villette (AG2R La Mondiale)Francis Wallart

THE SPONSORS

the sponsors in 2017ADIX AG2R LA MONDIALE ANIOS AUCHAN RETAIL FRANCE BASF BRUNEAU EURABIO FONDATION BEL LACTALIS M COMME MUTUELLE VERSPIEREN

Sponsorship contacts: Cédric Bouquet - +33 (0)3 20 87 72 67 - [email protected]édric Caravetta - +33 (0)3 20 87 71 20 - [email protected]

"Institut Pasteur de Lille is a leading organisation in the scientific sector. Eurabio is proud to share certain common values through collaborations and sponsorship. »

Thierry Mathieu, Scientific Director for

France of the Synlab group and chairman of Eurabio



FINANCING OF THE NEW MUSEUM

"We chose to support the renovation of the museum of Institut Pasteur de Lille because we knew that it was possible to do something exceptional. It's important that it should be open to the general public and our customers from throughout the world in order to showcase the scientific excellence of this campus."

Thierry Letartre, managing director of Anios Laboratories

The patronage of Anios laboratories was used to fund the creation of the new museum, which was opened in September 2017. This new contemporary museum traces the history of the foundation and its great discoveries.

The year 2017 was punctuated by many events and achievements. Each partnership led by Institut Pasteur de Lille seeks to be unique.

Through corporate patronage, Institut Pasteur de Lille has been able to benefit from the expertise of the consulting firm Adix on best practices in patronage activities. A jointly organised event on the theme of occupational health raised awareness among the businesses of the region.

shAring of sKiLLs

with Adix

Institut Pasteur de Lille hosted the Lille stage of the sponsors' Tour de France. According to François Debiesse, chairman of ADMICAL, "the Hauts-de-France region has always had a tradition of solidarity and mutual aid. Patronage helps to find solutions to create connections in our society."

Solidarity fundraisers

KIABI 335 employees of KIABI and Institut Pasteur de Lille took part in the "Smart Mobility, let's do it!" challenge. What's the objective? To promote the importance of regular physical activity and raise funds to fund research projects on longevity at Institut Pasteur de Lille. In total, 75 teams completed nearly 30 million steps, i.e. ½ the way around the earth and collected € 6,000!

WEEMBI SOLID'AIR is a unique collective action that revolves around a new challenge involving the world of wind tunnels: 24 consecutive hours in a free fall simulator, for the benefit of scientific research. With each booked initiation flight, Weembi donated € 15 to the foundation.

DALKIA 25 Dalkia employees ran the half-marathon under the banner of the institute during the 2017 event held in Lille. The idea: for every kilometre covered, €2 is donated to research.

touR de fRance sPonsoRs of the adMicaL,the fRench association foR the PRoMotion of PatRonage

A historic partnership on the Route du Louvre, which raised € 15,000 in 2017. The presence of Institut Pasteur de Lille on this type of fundraising event is essential and gets people involved in the research theme of the foundation.

pArticipAtion in the 2017 route du

Louvre thAnKs to the pArtnership with Ag2r

LA mondiALe

Diversity of achievements

"By choosing to support the scientific work and activities

of Institut Pasteur de Lille, we are lending our support to the

progress of medicine. We are happy to be able to share some

of the great compassionate core values this foundation. »

Laurent Perraguin, Bruneau Customer Relations Manager


"This new museum reflects the history of Institut Pasteur de Lille and its founders but also the impetus that drives the institute today: many future projects on the topic of longevity as well as new collaborations with the business world, as demonstrated by the patronage of Laboratoires Anios"

Pr Patrick Berche, General Director of Institut Pasteur de Lille

The mission assigned by Louis Pasteur to the institute was to arouse interest in science and pass on know-how. It was to provide the best possible response to these great values that Institut Pasteur de Lille decided to create a new museum. Entirely financed thanks to the patronage of Laboratoires Anios, a business involved in hygiene and disinfection, the museum of Institut Pasteur de Lille was opened on 22 September 2017. The layout of the museum was imagined and designed by Les Yeux d'Argos, a collective of artists dedicated to contemporary art and the digital world. The project management was entrusted to the firm of architects, M.P. Bouchez.

New Museumof Institut Pasteur de Lille



The museum is a mix between a cabinet of curiosities, a period laboratory and digital installations, revealing the mysteries of Institut Pasteur de Lille and its founders. This contemporary layout provides a tool that is undeniably suited to communicating science to all audiences. Arousing interest in science, research and health is a major concern for Institut Pasteur de Lille.

PAST, PRESENT, FUTURE

Founded in 1894 to tackle an epidemic of diphtheria, the Institut Pasteur de Lille quickly established itself as one of the leading research facilities in the fight against infectious diseases and a key player in public healthcare at the begin-ning of the 20th century.It is on this site that Calmette and Guérin dicovered the BCG vaccine against tuberculosis, the original strains of which are on show in the museum. Louis Pasteur and Lille are also linked with the history of alcoholic fermentation, which the scientist discovered at the Faculty of Sciences of Lille when he is the Dean in 1854. Since its creation, the Institut Pasteur de Lille, a private state-recognised public-interest foundation, has sought to help local populations by putting science at the service of health. At the time, certain private individuals, local communi-ties and industrialists came together to create the institute which, in addition to creating serums, educated the popula-tion about the rules of hygiene. Even today, the institute's campus is used by both researchers and health pro-fessionals who work on a daily basis to improve international scientific knowledge, discover the treatments of tomorrow and guide the population of the Hauts de France region and the businesses involved in health education and risk manage-ment. Although the health research and risk management objec-tives have shifted towards the diseases associated with ageing (cancer, cardiovascu-lar diseases, infectious and parasitic diseases, Alzheimer's disease, diabetes, etc...), the Institut Pasteur de Lille remains very attached to its roots and history.

Visitors immerse themselves in a fantasy world where the scientific research is poetically showcased in every corner of the museum. Installed on everyday furniture, they discover vials brought to life with video, a letter that writes itself by magic, a little mouse that crisscrosses the room, scales that wobble from left to right, etc. This contemporary exhibition has a very particular resonance in this location steeped in history...

Open to the public: Friday and Saturday 10 am - 12 noon / 2 pm - 5pm. The museum may be booked for private events.Contact: +33 (0)3 20 87 72 42 - [email protected]



A FOUNDATION ON THE MOVE


A FOUNDATION THAT IS ON THE MOVE

In 2017, the Foundation's project on the theme of longevity, in partnership with the Centre for Research on Longevity, took a step forward with the development of the health examinations centre in the Centre for Health and Longevity and the development of the Health Pollution Longevity Centre on the issues relating to pollution and the environment. These 3 strategic objectives (Research, Disease Prevention, Pollution) fit together perfectly thanks to knowledge that is shared and the interactions that are made possible between all the teams of the campus. Institut Pasteur de Lille has consolidated its strategic positioning as a leading centre addressing the issue of longevity and age-related diseases. Naturally, this development of the Foundation's missions to respond to the challenges of society involves changes to its organisation and governance and the optimisation of resources (financial, material and human).

the deveLopment of coLLABorAtions with the Business And industriAL worLdInstitut Pasteur de Lille develops its relations with the business and industrial worlds through scientific collaborations, specialist services, general-interest activities and corporate sponsorship. This openness, which is faithful to the origins of the institute, is necessary for the Foundation to fulfil its missions of research, specialist services and disease prevention in healthcare. Consequently, several collaborations were developed in 2017, first and foremost, with Auchan Retail France (specialist service for the Good Food programme, followed by sponsorship) or Dyson (specialist services in microbiological safety). Thanks to the permanent guest seats on the Board of Directors, business and industrial players can find out about and be in-volved in the management of the Foundation.

In addition, in order to be fully involved as a scientific and business operator in the Hauts-de-France, Institut Pasteur de Lille joined certain corporate networks in 2017, including the Club Gagnants and the Club des Entreprises Centenaires. Within this context, Institut Pasteur de Lille supported and participated in LinkLille in London in October 2017, a project promoting the Hauts-de-France and scientific excellence to British entrepreneurs.

A revised Board of Directors

To accompany this development, in order to be more open to the academic and business world, Institut Pasteur de Lille has changed its statutes and its Board of Directors. The main changes that have been made:

4Chairman of the Board elected from among the non-executive directors

4A seat for the Friends of the Foundation

4Creation of a committee4Non-executive director's

charter and operational control by an independent specialist

4Creation of permanent guest seats

THE BOARD MEETING OF 15 MARCH 2018 College of founders:Jacques Richir, Deputy mayor of Lille. Chairman of the Board of Directors (*)Marc Bodiot, Deputy mayor of LilleDominique Picault, Deputy mayor of LilleJérémie Crepel, Deputy mayor of LilleIsabelle Mahieu, Advisor City Council of Lille

College of institutional partners:François Kinget, City Councillor, representative of Métropole Européenne de Lille (MEL) Secretary (*)Nicolas Lebas, Vice-Chairman of Higher Education, research and universities, representative of the Hauts de France region. Vice-Chairman (*)

Nicolas Siegler, Departmental Advisor, representative of the County Council of the NordStewart Cole, General Manager of Institut PasteurYves Lévy, Chairman and Managing Director of the National Institute of Health and Medical Research (Inserm)Françoise Paillous, Regional Delegate for the Nord-Pas-de-Calais, representing the Chairman of the National Centre for Scientific Research (CNRS)Jean-Christophe Camart, Chairman of the Lille University

College of qualified personalities Prof François-René Pruvot, Chairman of the Medical Commission Establishment of Lille University HospitalPatrick Vacossin, Chamber of Notaries of the Nord. Treasurer (*)

College of Friends of the FoundationThierry Letartre, managing director of ANIOS. member of the office (*)

(*) members of the board



The organisation charts

scientific

Centre for research on longevity

Health Longevity Center

Pollution Health Longevity Centre Platforms

Infection and Immunity Center of Lille

Dr Camille Locht

Risk Factors and Molecular Pathways of Aging-Related Diseases

Pr Philippe Amouyel

Nuclear receptors, cardiovascular diseases

and diabetes Pr Bart Staels

M2SV : Drugs and Molecules for living

systemsPr Benoît Déprez

Integrative genomics and modeling of

metabolic diseases Pr Philippe Froguel

Mechanisms of tumorigenesis and targeted therapiesPr Yvan de Launoit

Health Longevity Centre medical management

Pr Eric Boulanger

Disease prevention centre and health

examinationsDr Gwenaëlle Floch

Health education Eric Guiot

Vaccination Dr Emmanuel Dutoit

Nutrition Dr Jean-Michel Lecerf

Microbiological safety unit

Dr Michèle Vialette

High Security Laboratory

Damien Legrand

Genetic toxicology laboratory Dr Fabrice Nesslany

PLEHTA platform Fabrice Infanti

Genomic analysis Nathalie Fiévet

Cellular imagingBiCel EquipEx ImaginEx

BioMed Frank Lafont

LIGAN Genomics EquipEx

Pr Philippe Froguel

Screening HTS ADME PK Pr Benoît Déprez

Nuclear magnetic resonance

Isabelle Landrieu

Transcriptomics and Applied Genomics

David Hot

Chemistry Systems Biology

Oleg Melnyk

Proteomics and analysis of modified peptides

Dr Camille Locht

General DirectorPr Patrick Berche


AdministrAtive

Deputy general directorDidier Bonneau

Assistant manager

Sylvie Amoravain

Administrative and financial management

Didier Bonneau

Administrative department of the Health Longevity

CentreCathy Brassart

Research administration

departmentFabienne Jean

FINANCES

Accounting Laurence Serras

Management control Sabine Roche

Cash accounting Alain Rosselle

Human resources Claire Bresler

Information technology

Bertrand Poulet

Infrastructure and general resources

Yves Dailly

Health and safety Charles Quentin

Legal and research promotion

Maxime Diot

Real estate Virginie Drelon

Quality Anne-Laure Charlent

98MEN

232WOMEN

509EMPLOYEES AND

TRAINEESOTHER

INSTITUTIONS *

* INSERM, CNRS, UNIVERSITIES, STARTUPS ...

30NATIONALITIES

330EMPLOYEES

INSTITUT PASTEURDE LILLE

839 empLoyees on cAmpus

Purchasing Reception Mehdi Zaam


Communications and sponsorship

departmentCédric Bouquet


An organisation undergoing transformation

At the forefront of this chAnge, there hAve Been the foLLowing importAnt frAmeworK projects for the foundAtion: 4 new statutes of the Foundation 4 two CPER-CTRL calls for projects on

Longevity4 the development of its disease prevention

centre4 creation of Pollution Health Longevity Centre4 installation of the Eurabio medical analysis

laboratory at the Pasteur Lille Campus4 the museum renovation thanks to the

patronage ofAnios

But ALso, the orgAnisAtionAL And operAtionAL projects, nAmeLy:

4 voluntary commitment to the regulations applicable to public contracts

4 enhancement of the management control4 creation of an IT continuity plan (backup,

archiving and redundancy)4 the CNIL audit4 review of projects in relation to the audit on

governance and conflicts of interest

to AccompAny these chAnges, the mAnAgement, in AssociAtion with the BoArd And the Authorities, hAs set up A numBer of tooLs:

4 a training policy that includes sessions on management and support for change

4 an improvement of internal communication with new tools (new intranet, internal newsletters, special newsletter, property projects, dynamic screens)

4 internal events for employees and internal visits of departments

4 semi-annual staff meetings and an annual event for staff every year in June

4 welcome sessions every month and a booklet for new recruits

4 staff reviews 4 restoration of the annual meetings and their

follow-up4 an Ecocampus approach with workshops for

staff4 a CSR process

in Addition, worKing conditions Are tAKen into considerAtion with the foLLowing:

4 modernisation of technical resources 4 a new company restaurant 4 a renovated sports hall4 renovated premises and in the process of

being renovated4 deployment of Wi-Fi on the campus4 right to disconnection

TECHNOLOGY PLATFORMS

OF LABORATORIES HEALTH CHECK-UPS SCIENTIFIC PAPERS

VACCINATIONSCONDUCTED

Like many organisations, Institut Pasteur de Lille is developing within a changing environment and must adjust its positioning, strategy and organisation to optimise its activities, ensure the long-term viability of its resources and meet the challenges of tomorrow in terms of health. For this reason, the Foundation strives to support these changes internally as much as possible.Since 2016, the management of Institut Pasteur de Lille has also been developing its management tools. This includes a multi-year plan composed of objectives, new tools for managing activities or even the optimisation of the available space in order to group together activities in order to make work easier for everyone.

10 50 000M2 15 132 377 26 000

Key figures



CSR commitment

ORGANIZATION

Governance and conflict of interest audit

Mixed composition of the board of directors: representatives of local communities, scientific world, etc.

LOCAL PLAYER

Responsible collective catering with our contractor, Envies de Saison

Individualised medical check-ups and recommendations (60% vulnerable people)

Research Education with Kid Campus

Withdrawal of vegetable baskets every week with Destinations Légumes

Participation in the cultural and tourist heritage of the city of Lille thanks to the Museum of Institut Pasteur de Lille

Job creation: welcoming foreign researchers, emerging teams, sandwich course students

WELL BEING AT WORK

Training: a budget that is twice that of the legal requirement

Social dialogue that is regular and transparent at the bi-annual staff meetings

Protection of pregnant women for positions exposed to chemical risks

Housing assistance for employees with Action Logement

Flexible hours

Subsidy for collective catering

ENVIRONMENT

Energy audit of the Campus

Management of hazardous waste

Sorting and recycling of ordinary waste

"Eco-Campus" participatory approach

Winner of the 2017 Mobility Challenge – Best active mode rate category (establishment of more than 500 employees)

EQUAL OPPORTUNITIES

6% of employees who have a disability



Uses/Resources€14.8 MILLION SPENT ON RESEARCH IN 2017Financing for the Institut Pasteur de Lille's missions comes from a variety of private and public sources.

In 2017, the Institut Pasteur de Lille spent €26.5 million on its principal missions of research (€14.8 million), prevention and public information (€9.1 million).

The €14.8 million for research breaks down into:

€ 5.1 M

€ 2.8 M

€ 0.9 M

€ 1.0 M

€ 1.6 M

€ 2.7 M

€ 0.7 M

foR infectious and infLaMMatoRy diseases

foR the Running of technoLogicaL PLatfoRMs

foR canceR ReseaRch

foR the discoveRy of Medicines

foR ReseaRch on caRdiovascuLaR and MetaboLic diseases

foR caRdiovascuLaR and neuRodegeneRative diseases

foR genetic and MetaboLic diseases



61%

SOCIAL MISSIONSNOT MUTUALIZED COSTS

COSTS TO CALLFOR PUBLIC GENEROSITY

LOADS RELATED TO RESEARCHGRANTS

CENTRALOPERATING COSTS

MUTUALIZEDOPERATING COSTS

USES2017

%

28%

7%

1%

3%

OTHER PRIVATE FUNDS INCLUDINGBUSINESS PATRONAGE (2/3)

PUBLIC GENEROSITY(DONATIONS AND LEGS)

RESOURCESAFFECTED TO

SOCIALMISSIONS 2017

%

GRANTS AND OTHERPUBLIC COMPETITIONS

OTHER PRODUCTSNOT ASSIGNED

41%

9%

37%13%

resources

uses

€ 30 m

€ 24.8 m



SCIENTIFIC PUBLICATIONS

Evolution in scientific productions 2013 2014 2015 2016 2017Number of publications (with epub) 313 327 346 337 339Number of publications with IF ≥ 20 14 6 14 17 7Number of publications with 10 > IF ≥ 20 31 38 35 29 38Number of publications, led by Pasteur Lille (1st, 2nd or last writer)

157(50%)

181(55%)

189(52%)

162(48%)

178(52%)

2017 Distributionby research group

2017 English-language scientific publications by research group

CIIL

Santépublique(U1167)

Maladiescardiovasculairesetdiabète(U1011)

Cancer(UMR8161)

ServicedenutriBon

Maladiesmétaboliques(UMR8199)

Plateformestechnologiques

Découvertedemédicaments

ToxicologiegénéBque

PrévenBonsanté

with epub

without epub

CIIL

Santépublique(U1167)

Maladiescardiovasculairesetdiabète(U1011)

Cancer(UMR8161)

ServicedenutriBon

Maladiesmétaboliques(UMR8199)

Plateformestechnologiques

Découvertedemédicaments

ToxicologiegénéBque

PrévenBonsanté


List of scientific publications whose impact factor (IF)* is greater than 10. All publications are available on our website.


Gross B, Pawlak M, Lefebvre P, Staels B. PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Nat Rev Endocrinol. 2017 Jan;13(1):36-49. doi: 10.1038/nrendo.2016.135. Epub 2016 Sep 16.

Guinet-Charpentier C, Lepage P, Morali A, Chamaillard M, Peyrin-Biroulet L. PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Gut. 2017 Jan;66(1):194-195. doi: 10.1136/gutjnl-2015-311058. Epub 2016 Jan 27.

Hibar DP, Adams HH, Jahanshad N, Chauhan G, Stein JL, , Chouraki V, …, , Amouyel P, …, Seshadri S, Thompson PM, Ikram MA. Novel genetic loci associated with hippocampal volume. Nat Commun. 2017 Jan 18;8:13624. doi: 10.1038/ncomms13624.

Webb TR, Erdmann J, Stirrups KE, Stitziel NO, …, Amouyel P, …, Schunkert H, Deloukas P, Kathiresan S, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease. J Am Coll of Cardiol, Vol 69, Issue 7, February 2017, DOI: 10.1016/j.jacc.2016.11.056.

Schmidt AF, Swerdlow DI, Holmes MV, Patel RS, Fairhurst-Hunter Z, …, Froguel P, Thuillier D, …, Bonnefond A, …, Hingorani AD; UCLEB consortium, Sattar N. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2017 Feb;5(2):97-105. doi: 10.1016/S2213-8587(16)30396-5. Epub 2016 Nov 29.

Carrat GR, Hu M, Nguyen-Tu MS, Chabosseau P, Gaulton KJ, …, Froguel P, Solimena M, McCarthy MI, Rutter GA. Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice. Am J Hum Genet. 2017 Feb 2;100(2):238-256. doi: 10.1016/j.ajhg.2017.01.011. Epub 2017 Jan 26.

Dubois V, Eeckhoute J, Lefebvre P, Staels B. Distinct but complementary contributions

of PPAR isotypes to energy homeostasis. J Clin Invest. 2017 Apr 3;127(4):1202-1214. doi: 10.1172/JCI88894. Epub 2017 Apr 3.

Justice AE, Winkler TW, Feitosa MF, Graff M, Fisher VA, …, Bonnefond A, …, Yengo L, …, Lobbens S, …, Froguel P, …, Tiemeier H, …, Borecki IB, North KE, Cupples LA. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun. 2017 Apr 26;8:14977. doi: 10.1038/ncomms14977.

Cortot AB, Kherrouche Z, Descarpentries C, Wislez M, Baldacci S, Furlan A, Tulasne D. Exon 14 Deleted MET Receptor as a New Biomarker and Target in Cancers. J Natl Cancer Inst. 2017 May 1;109(5). doi: 10.1093/jnci/djw262.

Chávez-Talavera O, Tailleux A, Lefebvre P, Staels B. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia and NAFLD. Gastroenterology. 2017 May;152(7):1679-1694.e3. doi: 10.1053/ j.gastro.2017.01.055. Epub 2017 Feb 15.

Sayed IM, Verhoye L, Cocquerel L, …, Montpellier C, …, Wychowski C, Dubuisson J, …, Izopet J, Michiels T, Meuleman P. Study of hepatitis E virus infection of genotype 1 and 3 in mice with humanised liver. Gut. 2017 May;66(5):920-929. doi: 10.1136/gutjnl-2015-311109. Epub 2016 Mar 22.

Lemesle G, Tricot O, Meurice T, Lallemant R, Delomez M, …, Lamblin N, Bauters C. Incident Myocardial Infarction and Very Late Stent Thrombosis in Outpatients With&Stable Coronary Artery Disease. J Am Coll Cardiol. 2017 May 2;69(17):2149-2156. doi: 10.1016/j.jacc.2017.02.050.

Juge PA, Borie R, Kannengiesser C, Gazal S, Revy P, Wemeau-Stervinou L, …, Bonnefond A, …, Froguel P, …, Wallaert B, …, FREX consortium, Boileau C, Crestani B, Dieudé P. Shared genetic predisposition in rheumatoid arthritis-interstitial lung disease and familial pulmonary fibrosis. Eur Respir J. 2017 May 11;49(5). pii: 1602314. doi: 10.1183/13993003.02314-2016. Print 2017 May.

Sanges S, Prévotat A, …, Hachulla É, Copin MC, Launay D. Haemodynamically proven pulmonary hypertension in a patient with GATA2 deficiency-associated pulmonary alveolar proteinosis and fibrosis. Eur Respir J. 2017 May 11;49(5). pii: 1700178. doi: 10.1183/13993003.00178-2017. Print 2017 May.

Maïssa N, Covarelli V, Janel S, Durel B, Simpson N, …, Lafont F, Nassif X, Marullo S, Bourdoulous S. Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4. Nat Commun. 2017 Jun 1;8:15764. doi: 10.1038/ncomms15764.

Dubois-Chevalier J, Dubois V, Dehondt H, Mazrooei P, Mazuy C, …, Gheeraert C, Penderia G, Baugé E, Derudas B, Hennuyer N, Paumelle R, Marot G, …, Staels B, Lefebvre P, Eeckhoute J. The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions. Genome Res. 2017 Jun;27(6):985-996. doi: 10.1101/gr.217075.116. Epub 2017 Apr 11.

Dourlen P, Fernandez-Gomez FJ, Dupont C, Grenier-Boley B, Bellenguez C, Obriot H, …, Sottejeau Y, Chapuis J, Bretteville A, Abdelfettah F, Delay C, Malmanche N, …, Amouyel P, …, Buée L, Lambert JC, Dermaut B. Functional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology. Mol Psychiatry. 2017 Jun;22(6):874-883. doi: 10.1038/mp.2016.59. Epub 2016 Apr 26.

Chapuis J, Flaig A, Grenier-Boley B, Eysert F, Pottiez V, Deloison G, Vandeputte A, Ayral AM, Mendes T, Desai S, …, Leroux F, Herledan A, Demiautte F, …, Malmanche N, …, Dourlen P, Song OR, …, Amouyel P, Deprez B, Brodin P, Lambert JC, ADGC, Alzheimer’s Disease Neuroimaging Initiative. Genome-wide, high-content siRNA screening identifies the Alzheimer’s genetic risk factor FERMT2 as a major modulator of APP metabolism. Acta Neuropathol. 2017 Jun;133(6):955-966. doi: 10.1007/s00401-016-1652-z. Epub 2016 Dec 8.

IF between 10 and 20



Stefani C, Gonzalez-Rodriguez D, Senju Y, Doye A, Efimova N, Janel S, …, Lafont F, Svitkina T, Lappalainen P, Bassereau P, Lemichez E. Ezrin enhances line tension along transcellular tunnel edges via NMIIa driven actomyosin cable formation. Nat Commun. 2017 Jun 23;8:15839. doi: 10.1038/ncomms15839.

Chinetti-Gbaguidi G, Daoudi M, Rosa M, Vinod M, Louvet L, Copin C, Fanchon M, Vanhoutte J, Derudas B, Belloy L, …, Susen S, Massy ZA, Eeckhoute J, Staels B. Human Alternative Macrophages Populate Calcified Areas of Atherosclerotic Lesions and Display Impaired RANKL-Induced Osteoclastic Bone Resorption Activity. Circ Res. 2017 Jun 23;121(1):19-30. doi: 10.1161/CIRCRESAHA.116.310262. Epub 2017 Apr 24.

Le Guennec K, Quenez O, Nicolas G, Wallon D, Rousseau S, …, Bellenguez C, Grenier-Boley B, …, Amouyel P, …, Lambert JC, Hannequin D, Campion D, Rovelet-Lecrux A. 17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression. Mol Psychiatry. 2017 Aug;22(8):1119-1125. doi: 10.1038/mp.2016.226. Epub 2016 Dec 13.

Yadav P, Ellinghaus D, Rémy G, Freitag-Wolf S, Cesaro A, …, Delacre M, …, Pichavant M, …, Gosset P, …, Chamaillard M, Dempfle A, Andersen V. Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice. Gastroenterology. 2017 Aug;153(2):550-565. doi: 10.1053/j.gastro.2017.05.010. Epub 2017 May 12.

Boucly A, Weatherald J, Savale L, Jaïs X, Cottin V, …, de Groote P, …, Simonneau G, Humbert M, Sitbon O. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J. 2017 Aug 3;50(2). pii: 1700889. doi: 10.1183/13993003.00889-2017. Print 2017 Aug.

Marciniak E, Leboucher A, Caron E, Ahmed T, Tailleux A, Dumont J, …, Bantubungi K, Lancel S, …, Vallez E, …, Grenier-Boley B, …, Staels B, Amouyel P, Balschun D, Buee L, Blum D. Tau deletion promotes brain insulin resistance. J Exp Med. 2017 Aug 7;214(8):2257-2269. doi: 10.1084/jem.20161731. Epub 2017 Jun 26 .

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IF greater than 20

* The impact factor of a journal is the average number of citations of articles in the journal compared to the number of articles published by the journal. By default, it is calculated for a two-year publication period.



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