DEFEATING EBOLA

We The Microbiologist

From The Editors Desk

It seems to be long time We Thefuture microbiologists. From the time of WTM’s initial magazines to article magazine, then to Microbiology Today magazine and finally launched Micrographia Today. It’s not even year for the new nareaders of the magazine made us highlight important stories of Microbiology to reach authors at different levels.

This time the cover story brings on the recent spread of Ebola virusincubation period of the virus is so low that it is difficult to treat. Till now we don’t have any vaccine to stop this virus or may not even think of the extinction of the virus. The cover story highlights the recalled ZMapp. The vaccine has proved to be positive in animal model such as monkey but will it stop spreading in humans? Will ZMapp able to defeat Ebola?

“Dream high, drive carefully, unite together;

Thank you,Swapnil Vichare

[email protected]

Editor - in - ChiefMr. Swapnil Vichare

Co-Editor in ChiefMr. Saumyadip Sarkar

EditorMr. Golam Moktadir Khan

ReviewersBapi JhaBamgboseShrikant SonawaneNehaKunlere 'HiMd. Mehedi Hasan MagnetDr.


2

From The Editors Desk

It seems to be long time We The Microbiologist is lengthening the knowledge among bright future microbiologists. From the time of WTM’s initial magazines to article magazine, then to Microbiology Today magazine and finally launched Micrographia Today. It’s not even year for the new name of the magazine but the wide response for the interest provided by the readers of the magazine made us highlight important stories of Microbiology to reach authors at different levels.

This time the cover story brings on the recent spread of Ebola virus. The extent of the spread is high and the incubation period of the virus is so low that it is difficult to treat. Till now we don’t have any vaccine to stop this virus or may not even think of the extinction of the virus. The cover story highlights the recent vaccine development called ZMapp. The vaccine has proved to be positive in animal model such as monkey but will it stop spreading in humans? Will ZMapp able to defeat Ebola? Read more in the cover story.

“Dream high, drive carefully, unite together; we will take this mission to newer heights”

Swapnil [email protected]

ReviewersBapi JhaBamgbose Princeteejay TimothyShrikant SonawaneNeha AilaniKunlere 'Hi-Dee' IdowuMd. Mehedi Hasan MagnetDr. Azhar Bhatt

Disclaimer: Views and opinion expressed in this magazine are not those of We The Microbiologist, it’s of the authors and writers. We, at We The Microbiologist Micrographia Today do our best to verify the information published but do not take any responsibility of absolute accuracy of the information. We The Microbiologist does not accept any responsibility for any decision taken by readers based on the information provided in the magazine. No part of this magazine can be reproduced without prior written permission.

[Note: Images for the cover page is derived from google images]

2014

Microbiologist is lengthening the knowledge among bright future microbiologists. From the time of WTM’s initial magazines to article magazine, then to Microbiology Today magazine and finally launched Micrographia Today. It’s not even a

me of the magazine but the wide response for the interest provided by the readers of the magazine made us highlight important stories of Microbiology to reach authors

. The extent of the spread is high and the incubation period of the virus is so low that it is difficult to treat. Till now we don’t have any vaccine to stop this

cent vaccine development called ZMapp. The vaccine has proved to be positive in animal model such as monkey but will it stop spreading in

we will take this mission to newer heights”

Disclaimer: Views and opinion expressed in this magazine are not those of We The Microbiologist, it’s of the authors and writers. We, at We The Microbiologist Micrographia Today

best to verify the information published but do not take any responsibility of absolute accuracy of the information. We The Microbiologist does not accept any responsibility for any decision taken by readers based on the information provided

ne. No part of this magazine can be reproduced without prior written permission.

Note: Images for the cover page is derived from google


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2014

Leadership Board

PresidentMs. Harshada Kasar

[email protected]

Principal SecretaryMr. Bapi Jha

[email protected]

Managing DirectorMr. Saumyadip Sarkar

[email protected]

Organizing SecretaryMr. Trinankur Bhattacharya

[email protected]

Editor - in – ChiefMr. Swapnil Vichare

[email protected]

EditorMr. Golam Moktadir Khan

International Outreach CoordinatorsMr. Golam Moktadir Khan

Bangladesh (bd.wethemicrobiologist.in)

Mr. Bamgbose Princeteejay TimothyNigeria

Mr. Sajjad AhmadPakistan (pk.wethemicrobiologist.in)

www.wethemicrobiologist.in/magazine.html


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Table of Contents

S.No TITLE AUTHOR PAGE NO.

1. NEWS Correspondents 05

2. Unleashing the secret of“Bacterial Genetics”

Correspondents 16

3.Cover Story

Defeating EBOLACorrespondents 18

4.Structure Based Viral Vaccine Design: A

Changing Face of VaccinologyR. Santhamani, and I. Sophia

21

5.Novel Virus: crAssphage discovered in half

the world’s populationSaumyadip Sarkar

32

6. A talk with Balaram Mahapatra Correspondents 34

7. Opportunities Correspondents 41

*NOTE: - The Image on the Cover Page is taken from Google Images and is edited.


NEWS

Flipper Mystery of t

Researchers finally believe they have identified the hidden identity of the bacteria after this

wonderful research published in

Medical School and Ohio State University. The research finally revealed how

enzyme can flip the cargo from inside to outside of the cell.

passageways that export these contents for the wall forma

they carried out multiple experiments.

Antibiotics like penicillin and bacitracin has been their important target on the cell wall.

When these antibiotics interact with the bacteria, they lyse and die. With the development

of new strains of drug resistant bacteria researchers carried forward for the development of

new antibiotics. The reason was the prior success which made them the target, although

least been tried to discover the new ways of blocking the cell wall develop

Earlier, Scientists have shown that how the building blocks of the cell wall are assembled

inside the cell and then how these blocks are brought together for the formation of cell wall.


5

Mystery of the Bacterial Cell Wall Revealed


wonderful research published in Science by the team of microbiologists from Harvard

Medical School and Ohio State University. The research finally revealed how

enzyme can flip the cargo from inside to outside of the cell.

The cell wall surrounds the bacterial membrane which is

like a balloon inflated and may burst without it. Cell wall

provides membrane integrity from the external or

surrounding pressures involved like osmotic pressure.

The content of the cell wall are made inside the cell and

has to be carried outside the membrane of the bacterial

cell for the complete formation of the cell wall. The

passageways that export these contents for the wall formation remained mysteries although

they carried out multiple experiments.





least been tried to discover the new ways of blocking the cell wall develop



2014

he Bacterial Cell Wall Revealed


by the team of microbiologists from Harvard

Medical School and Ohio State University. The research finally revealed how a new

The cell wall surrounds the bacterial membrane which is

like a balloon inflated and may burst without it. Cell wall

provides membrane integrity from the external or

nvolved like osmotic pressure.

The content of the cell wall are made inside the cell and

has to be carried outside the membrane of the bacterial

cell for the complete formation of the cell wall. The

tion remained mysteries although





least been tried to discover the new ways of blocking the cell wall development.




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But the point that is missed out is how these blocks are transported outside the membrane

for making complete cell wall.

Building blocks of the cell wall are made up of sugar molecules linked to a lipid carrier that

can anchor to the cell membrane. The hypothesis was the bacterial cells might possess a

transport protein which can able to undergo flip-flop reaction to make the lipid linked

building blocks to move from one side of the membrane to another. Although this finding of

the flip-flop protein, called flippase remained a mystery. The scientists from HMS and OSU

have finally made the biggest contribution towards microbiological science by finding the

evidence of the flippase, MurJ. The researchers now looking forward to believe that they

can come out with some successful antibiotics that can stop this flip-flop reaction.

The research that has been carried out is much more interesting. The team developed a

wonderful method where colicins or the protein toxins that like the molecular razor can

slice the sugar blocks from the lipid anchors. Thus releasing free sugar blocks, which are

not produced by the bacterial cells around the medium they are growing into. Because

toxins cannot penetrate membrane, instead they blob the sugar molecule outside. If the

sugar molecules are found to be outside then flipping reaction is underway.

The next step was the challenge, where they used the combination of both genetic and

chemical techniques to know what happens when flippases are switched off. Mutated

versions of MurJ bacteria, which are chemically susceptible to some, were developed.

When the chemicals are introduced to the mutated forms of the bacteria, none of the colicin

generated sugar molecules were found in the medium. Thus the result proved that flippase

has been stopped and provides a novel identification.

The experiments were performed on E.coli but researchers are looking ahead believing that

this might be the common phenomenon in all the bacteria possessing cell wall. The

researchers are now working on the structure of the newly identified new MurJ and its flip-


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flopping mechanism. Thus it may provide the plug to introduce new antibiotics that can

block this mechanism. The research was funded by the National Institute of Health.

News Source: Harvard Medical School.

New Mechanism in Gene Regulation Revealed

The information encoded in our genes is translated into proteins, which ultimately mediate

biological functions in an organism. Messenger RNA (mRNA) plays an important role, as it

is the molecular template used for translation. Scientist from the Helmholtz Zentrum

München and the Technische Universität München, in collaboration with the Centre for

Genomic Regulation (Barcelona, Spain) and colleagues in Grenoble, France, have now

unraveled a molecular mechanism of mRNA recognition, which is essential for

understanding differential gene regulation in male and female organisms. The results are

published in the scientific journal Nature.

The number of genes in humans, mice and fruit flies is almost identical, around 20,000, and

thus cannot explain the phenotypic differences between these organisms. Thus, for the

evolution of life not only the number of genes but also the regulation of these genes plays a

critical role. Upon transcription of the DNA, mRNA is produced as an initial step, which

subsequently functions as template for the synthesis of proteins. Protein synthesis is

regulated by the binding of regulatory proteins to the mRNA. How these proteins

specifically recognize the RNA has been poorly understood to date.

An international team, led by Helmholtz Zentrum München (HMGU) and Technische

Universität München (TUM), has now determined the three-dimensional structure of such a

regulatory protein-RNA-complex. Crystallography and NMR spectroscopy analysis

performed by the Munich team was complemented with small angle scattering data

performed at the Institut Laue Langevin in Grenoble. The scientists studied the specific


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complex formed between the regulatory proteins Sxl (Sex-lethal) and Unr (Upstream-of-N-

Ras) with mRNA in the fruit fly model. This protein complex is essential to ensure that the

expression of genes located on the two female (XX) X-chromosomes equals that of genes

located on the single male (XY) X-chromosome. This guarantees that comparable protein

concentrations are achieved in both sexes, which is essential for viability of fruit flies.

A paradigm for gene regulation

The three-dimensional structure now reveals how multiple proteins collaborate for highly

specific recognition of the mRNA. "Our results represent a paradigm for the regulation of

various essential cellular processes at the level of mRNA," explains Sattler, director of the

Institute of Structural Biology at HMGU. The specific recognition of mRNA is achieved by

cooperation of several RNA-binding proteins, even though these proteins individually

exhibit poor binding affinity and are involved in distinct processes in the cell. By

combining multiple proteins, the number and variety of biological processes that can be

regulated by a relatively small number of regulatory RNA binding proteins, is greatly

expanded.

The authors expect that this principle represents an essential and widespread mechanism of gene regulation in higher organisms, where mutation or misregulation of homologous proteins has been implicated in disease.

News Source: Science Daily.

Sequencing of Five African Fishes Reveals Diverse Molecular

Mechanisms Underlying Evolution

In an effort to understand the molecular basis of adaptation in vertebrates, researchers

sequenced the genomes and transcriptomes of five species of African cichlid fishes. A

research team led by scientists at the Broad Institute of MIT and Harvard uncovered a

variety of features in the cichlid genomes that enabled the fishes to thrive in new habitats

and ecological niches within the Great Lakes of East Africa. In addition to helping explain


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the complex genomic mechanisms that give rise to incredible diversity among cichlid

fishes, the findings from these "natural mutants" shed new light on the molecular process of

evolution in all vertebrate species.

The new study, done in collaboration with scientists at Eawag Swiss Federal Institute for

Aquatic Sciences and Georgia Institute of Technology, in addition to more than 70

scientists from the international cichlid research community, appears in the September 3

advance online edition of Nature.

"Our study reveals a spectrum of methods that nature uses to allow organisms to adapt to

different environments," said co-senior author Kerstin Lindblad-Toh, scientific director of

vertebrate genome biology at the Broad Institute, professor in comparative genomics at

Uppsala University, and the co-director of Science for Life Laboratory, Sweden. "These

mechanisms are likely also at work in humans and other vertebrates, and by focusing on the

remarkably diverse cichlid fishes, we were able to study this process on a broad scale for

the first time."

The African cichlid fishes are some of the most phenotypically diverse groups of organisms

on the planet, with over 2,000 known species. Some lakes are home to hundreds of distinct

species that evolved from a common ancestral species that left the Nile River to colonize

particular lakes. Like Darwin's finches, the cichlids are a dramatic example of adaptive

radiation, the process by which multiple species "radiate" from an ancestral species through

adaptation.

The researchers wanted to examine the cichlid genome as a model system and determine

what allowed these fishes to diversify broadly in a relatively short time. The researchers

sequenced the genomes and transcriptomes -- the RNA from ten tissues -- of five distinct

lineages of African cichlids. The sequenced species include the Nile tilapia, representing the

ancestral lineage, and four East African species: a species that inhabits a river near Lake

Tanganyika; a species from Lake Tanganyika colonized 10-20 million years ago; a cichlid


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species from Lake Malawi colonized 5 million years ago; and species from Lake Victoria

where the fish radiated only 15,000 to 100,000 years ago.

After analyzing the data, the researchers found a surprising number of genomic changes at

play. Compared to the ancestral lineage, the East African cichlid genomes possess: an

excess of gene duplications; alterations in regulatory, non-protein-coding elements in the

genome; accelerated evolution of protein-coding elements, especially in genes for

pigmentation; and other distinct features that affect gene expression, such as insertions of

transposable elements and regulation by novel microRNAs.

"It's not one big change in the genome of this fish, but lots of different molecular

mechanisms used to achieve this amazing adaptation and speciation," said Federica Di

Palma, co-senior author of the Nature study, formerly assistant director of vertebrate

sequencing and analysis at the Broad, and now director of science in vertebrate and health

genomics at The Genome Analysis Center in the UK.

Some changes in the genome appear to have accumulated before the species left the rivers

to colonize lakes and radiated into hundreds of species. This suggests that the cichlids were

once in a period of reduced constraint. During this time, the fishes accumulated diversity

through genetic mutations, and the relaxed constraint -- in which all individuals thrived, not

just the fittest -- allowed genetic variation to accumulate. As the fish later inhabited new

environmental niches within the lakes, new species could form quickly through selection. In

this way, a reservoir of mutations -- and resultant phenotypes -- represented a "genomic

toolkit" that allowed quick adaptation.

More work remains to fully dissect the mutations that cause each of the varying phenotypes

in cichlid fish and may involve the sequencing of many more cichlid species. This effort

could help explain how similar forms or traits evolved in parallel in different lakes,

converging on the same morphology through distinct lineages.

Using these "natural mutants" as a model system can shed light on human biology and

disease. "By learning how natural populations, such as fishes, adapt and evolve under


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selective pressures, we can learn how these pressures affect humans in terms of health and

disease," said Di Palma.

News Source: Science Daily.

Google Glass App Knows Your Age and Mood

Several billion years of evolution have gone into our capacity, as a species, to read body

language and facial cues. Fifty thousand years ago, we used this ability to avoid getting

smacked with a club by Thag, the caveman down the ravine. Now, we use it to sense

whether the barista is charmed with our wry smile.

The technology industry has only been at this game a few years, but results are ramping up

quickly thanks to the ongoing, slow motion collision between wearable computers, facial

recognition software and ubiquitous digital cameras.

Good Thinking! Brain-Control Google Glass

To wit: Researchers at the Fraunhofer ISS Institute in Germany are working on a Google

Glass application designed to read the emotional state of whomever you’re looking at.

According to the institute’s demo video -- see below -- the system can determine with

variable accuracy whether the subject is happy, sad, angry, surprised, or some combination

thereof.

The software, currently in development, uses the Google Glass camera along with the

institute’s existing SHORE (Sophisticated High-speed Object Recognition Engine) system.

The analysis engine has been deployed previously on other computer systems, but now

Fraunhofer has jammed the technology into narrow confines of Google Glass’ hardware

specs.


SHORE is a facial recognition system, essentially, though with the Glass app the system is

not intended to determine identity. Fraunhofer says all information is kept on board, so the

system can’t be used (yet) for going to the Cloud

online database.

Mood Sweater Automatically Shows Your Feelings

The system can, however, determine gender (with 94.3 percent accuracy) and estimate age

with a “6.85 annual mean absolute error.” No, I don’t know what

emotion detection numbers are generated by interpreting broad facial and body language

cues.

The technology is really more interesting in its implications than in what it’s designed to

achieve, as of now. Privacy concerns aside, imag

integrated facial recognition, database and augmented reality technology. That could come

in very handy at parties — Glass would put a name to a face, instantly and constantly,

disposing of many an awkward social situat

state dystopia, but still.

When we will have Vaccine for Ebola Virus

The news about the latest outbreak of Ebola virus in West

Africa shook the world

people. Guinea,

News channels call it as “totally out of control” and

unfortunately doctors cannot prescribe any effective vaccines.

Health care officials can only support patient’s immune

systems (regulating fluids, oxygen lev


12



system can’t be used (yet) for going to the Cloud and running a facial profile through an

Mood Sweater Automatically Shows Your Feelings


with a “6.85 annual mean absolute error.” No, I don’t know what that means either. The



achieve, as of now. Privacy concerns aside, imagine a Google Glass system with fully


Glass would put a name to a face, instantly and constantly,

disposing of many an awkward social situation. It would also mean a terrifying surveillance

When we will have Vaccine for Ebola Virus


Africa shook the world – as far recorded till now to be 1,200

people. Guinea, Sierra and Liberia all have confirmed cases.




systems (regulating fluids, oxygen levels, infection level, etc.),

2014



and running a facial profile through an


that means either. The



ine a Google Glass system with fully


Glass would put a name to a face, instantly and constantly,

ion. It would also mean a terrifying surveillance


as far recorded till now to be 1,200

Sierra and Liberia all have confirmed cases.




els, infection level, etc.),


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to fight off virus as much as can.

When we talk about vaccine against Ebola virus, may be just yet few years away. Earlier

research have made significant progress in the development of vaccines that have worked

nonhuman primates. It has not hard to put on to human tests. Scientific American

(http://www.scientificamerican.com/) spoke to Thomas Geisbert, a virologist in the

Department of Microbiology and Immunology at The University of Texas Medical Branch

at Galveston. He’s studied the Ebola virus since 1988 and is currently involved in vaccine

research and development. Here it is highlighted his views on the vaccine development

against Ebola virus.

Any promising vaccine against Ebola virus?

A few preventive vaccines have been developed to prevent from Ebola viruses which have

been tested in nonhuman primates. Some of these vaccines require three or more and some

require just one injection. These vaccines have been funded by US government and are

made at various stages of development, but unfortunately none has yet been licensed.

Now the important phase yet remains is to test it over humans. Scientists here get frustrated

because, they know vaccines protect animals but yet they are unknown about the regulatory

process for how to make things go faster.

The reason why human immune system cannot fight the virus off

The transmission of Ebola virus is through close contact and the first cell it affects are the

cells important for the primary immune system like the macrophages, monocytes and the

dendritic cells. These cells are most important to make things understand that something

foreign has entered into our body and anyhow it has to be encountered to fight it off. Thus it

has been difficult enough to make immune response against this virus. It’s like shutting

down or targeting the main power.


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What are the biological challenges of developing a vaccine against Ebola?

There are multiple vaccines which are replication defective, i.e. they do not replicate and

tend to be safer. There are some vaccines which are efficacious and they are replication

competent. They are usually not as dangerous as a wild type virus, but at certain points it

can show adverse effects.

“I would like to see a situation where we tried to advance our lead candidate vaccines as

fast as we can to get phase I studies done. I think we should start with the first responders—

the health care workers in areas of high risk. This outbreak is so unique because it’s

occurring in an area we’ve never seen it before and also because it seems there’s a higher

percentage of medical staff infected than we’ve seen before. I’ve seen all of these vaccines

work in numerous animals and I’ve never seen an adverse event from them. I appreciate the

safety concerns but it would be great if there were some way to fast-track this. People are

being exposed to Ebola and there’s a 60 to 90 percent chance they’re going to die—I think

we have to look at it in this context.” – as told to Scientific American.

Study Source: Scientific American.


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INTERNATIONAL YOUNG MICROBIOLOGIST COMPETITION 2014

ORGANIZED BY WE THE MICROBIOLOGIST AND MICROBIOLOGY WORLD

The registration and submission of the case study is open now.For details visit

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Contact at [email protected]


AUTHORS SPEAK

Unleashing the secret of“Bacterial Genetics”

Bacterial genetics is the subfield of genetics devoted to the study of bacteria. Bacteria serve as a good model for animal genetic studies. The pioneering work of bacterial genetics done by “Esther Lederberg” opened the door for some fundamental discoveries in microbial genetics.

"Shewasaverykeenobserverhaveescapedtheeyesandintellects

Esther Miriam Zimmer LederbergNovember11, 2006), emeritusprofessorimmunologyat Stanford Universitymicrobiologist.

Esther won a scholarship to initially intendedtostudyliterature, butshemajoredinbiochemistryfromHunterin1942,shecamestudygenetics where she completed masters in 1946.

She joined the brilliant youngLederbergashiswifeandasUniversityofWisconsin, where she

“Though she did pioneering work in genetics, but it was her husband who won a Nobel priceBritish newspaper. In 1956,IllinoisBacteriologistsawardedLederberg the Pasteur Medalcontributions to thefieldsofwasthiswork aswellashisdiscoveryofandbacterial transduction thatNobelPrizein1958. Estherand1966.


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AUTHORS SPEAK

Unleashing the secret of“Bacterial Genetics”

is the subfield of genetics devoted to the study of bacteria. Bacteria serve as a good model for animal genetic studies. The pioneering work of bacterial genetics done

opened the door for some fundamental discoveries in microbial

observerandpickedupbiologicalphenomenaintellectsofmostotherpeople”.

Esther Miriam Zimmer Lederberg (December 18, 1922 to professorofmicrobiologyand

University, was an American

attend Hunter College. She literature, buttoeveryone’ssurprise,

instead.AfterhergraduationcametoStanfordUniversityto

genetics where she completed masters in 1946.

young microbiologist, Joshua

hisresearchassociateattheshereceivedaPhD in 1950.

Though she did pioneering work in genetics, but it was her husband who won a Nobel price” So said an obituary in the

1956, the Society of JoshuaLederbergandEsther

Medal, for "their outstanding microbiologyandgenetics”.Itdiscoveryofbacterialconjugation

transduction thatwonJoshuaLederberg theandJoshuaweredivorcedin

2014

Unleashing the secret of

is the subfield of genetics devoted to the study of bacteria. Bacteria serve as a good model for animal genetic studies. The pioneering work of bacterial genetics done

opened the door for some fundamental discoveries in microbial

phenomenathatwould


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Contributions:

Estherpublishedherfirstseminaldiscoveryofabacterialviruslambda in1950, which becameausefulmodelforstudyingthebiologyofallviruses.

In1952, EstherandJoshLederbergmadeabrilliantlysimplediscoveryofa

techniquecalled “ReplicaPlating” which was usedinthestudyofbacterial

genetics (specificallyintheselectionofmutants).

DuringhertimeinWisconsinEstherLederbergalsodiscoveredthefertilityfactor, F,themediatorofbacterialconjugation. Thisledtotheunderstandingthatbacteriapossessedamobilegeneticelements, plasmids,transposons that served as a major source of biological variation.

Esther to take on the role of Curator of plasmids Bythemid- 70s, Estherwasaskedtotakeontheroleofcuratorofplasmids

worldwideby an international committee of scientists. Because of her knowledgeand thehigh regard inwhich shewasheldbyhercolleagues,EstherwasentrustedwithkeepingtheplasmidsinacollectionshekepthereatStanford.

Owing to the contributions and pioneering work of Esther Lederberg, it can be rightly stated that she wasabrilliant scientistandamajorcontributorof themost importantdiscoveriesingeneticscience. Though Estherhadtofaceanumberofhurdles, Shedidher research withextraordinarygrace,gentlenessandwitharespectandloveforsciencethatisimportanttorememberandemulate,especiallyatthistimewhenthepursuitofbasicknowledgeisbecomingsoverydifficult.EstherZimmerLederberghasanassuredplaceinthehistoryofscience.Itwillnotbeforgottensolongasthereisacivilization.


Cover Defeating EBOLA

Ebola virus has become the real bioFiloviridae family. There are 5types of Ebola virus that has been identified, where four is known to cause disease in humans. The disease is known to be highly infectious that can easily spread through close contact with body fluids, skin or even objects of the infected person. Ebola virus because of its short incubation period of 2-21became a reason of serious threat. The symptoms like fever, headache, drop of blood pressure, and stomach pain are the focus of the infection of Ebola and most of the people

Extent of the Outbreak of

A document released, where the UN health officials said that the disease “continues to accelerate”. The report continued to be around 40% of reported cases. As of august 28, Guinea, Nigeria, Sierra Leone and Liberia have reported 3069 cases of the disease the outbreak started in December and may be it will continue once there is a potent vaccine to stop or eradicate it.

The disease is so deadly that the virus causes high fever that is high enough to puncture the blood vessels and this leading to internal bleeding and ultimately to death. Till now 1552 deaths has been reported. WHO has reported that there is no vaccine to eradicate this deadly Ebola. WHO said to improve the public health infrastructure to cope with future threats. Most importantly many


18

Cover StoryDefeating EBOLA

Ebola virus has become the real bio-threat in the entire world. It is caused by a virus of family. There are 5types of Ebola virus that has been identified, where four is

known to cause disease in humans. The disease is known to be highly infectious that can easily spread through close contact with body fluids, skin or even objects of the

ted person. Ebola virus because of its 21 days which

became a reason of serious threat. The symptoms like fever, headache, drop of blood pressure, and stomach pain are the focus of the infection of Ebola and most of the people are found to be ignoring it. [

Extent of the Outbreak of Ebola [3]

A document released, where the UN health officials said that the disease “continues to accelerate”. The report continued to be around 40% of reported cases. As of august 28, Guinea, Nigeria, Sierra Leone and Liberia have reported 3069 cases of the disease since the outbreak started in December and may be it will continue once there is a potent vaccine to stop or

The disease is so deadly that the virus causes high fever that is high enough to puncture the blood vessels

rnal bleeding and ultimately to death. Till now 1552 deaths has been reported. WHO has reported that there is no vaccine

WHO said to improve the public health infrastructure to cope with future threats. Most importantly many international flights have been suspended.

2014

threat in the entire world. It is caused by a virus of family. There are 5types of Ebola virus that has been identified, where four is

. [2]

death. Till now 1552 deaths has been reported. WHO has reported that there is no vaccine WHO said to improve the public health infrastructure to cope

been suspended.


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2014

American Ebola patient Nancy Writebol, pictured here being wheeled into Emory University Hospital in Atlanta on (CBC News)

Ebola Drug – ZMapp [1]:

A new drug ZMapp can heal knock down Ebola, a new study say. It would be promising for treatment against this deadly virus if it can heal people as it worked on 18monkeys.

The recent research, published in journal Nature, researchers gave monkeys with ZMapp three to five days after they were infected with deadly Ebola viruses and almost after they started showing symptoms. It is almost long time after that this experimental Ebola treatment came to news front. Dr. Anthony, director of the National Institute of Allergy and Infectious Diseases, which had a role in the work.

In an additional study, the drug protected completely six monkeys given slightly different version of the virus, three days after injection in pilot test. These two studies on monkeys are for the first time ever done with ZMapp. The drug has the compound with three antibodies that can attach to cells infected with Ebola, allowing immune system to detect and knock down.

It is not sure that whether the drug can cure in humans. The incubation time which is quite different from the monkeys, where it takes around 21 days in humans. Moreover the infection in monkeys tested is in different manner than how humans are getting infected. Some researchers still claims that it may not be possible to provide window of opportunity to treat people, but it is encouraging to highlight that how animals recovered even in advance disease development.

The question does come about the response of the ZMapp drug in humans. Will they be surely providing a cure? Dr. Cameron Wolfe, Duke University infectious disease specialist answers “we don’t know”, when asked about the same and added “the drugs tell us nothing about side effects”.


ZMapp had never been tested on humans before two and Dr. Kent Brantly, who got infected with Ebola while working in Africa, were allowed to go for the try. Fortunatelypersons were allowed to go for the try. Inan ethical dilemma. Two later known died, where one is Liberian doctor and a Spanish priest.

Currently there is no ZMapp, the new batch upcoming need to go through some screen before it is officially launched. It may be tried again in future. The proper dose still remains unknown. The drug which has grown in tobacco plants, and developed by US government support will take several months from now, as mentioned by ZMapp’s makerBiopharmaceutical Inc., San Diego.

The deadly Ebola has killed more than 1,500 people in 2014 and World Health Organization has reported that it may reach as many as 20,000cases before the outbreak brought under control. There is no as such till now approved vaccine that can be treated against Ebola, but just supportive care is required. A recent research from the researchers of Massachusetts claim that the Ebola virus is mutating rapidly, after screening initial patients in Sierra Leone with around 400 genetic modifications[4]. This may give a reZMapp manufacturers not working as a true vaccine. Efforts now been made to fincases and tracking their contacts to limit down the flow of the disease. Ebola spreads mostly via blood contacts and other body fluids. US Federal health officials start their human trials on Ebola vaccine as soon as it proves panimals.

Ref:

1. ZMapp cures monkeys of Ebola virus. CBS News, August 29, 2014.2. What is the Ebola virus disease survival rate? Health News, 3. Ebola virus outbreak can hit 20,0004. Ebola virus ‘is mutating rapidly’, expert warns. Mail Online,


20

Erica Ollmann Saphire at Scripps event showing a model of the Ebola surface(white) with three ZMapp antibodies attached.

ZMapp had never been tested on humans before two American aid workers, who got infected with Ebola while working in Africa, were allowed

both recovered. Due to limited supply, five more infected persons were allowed to go for the try. In recent weeks, the use of untested drug has incited an ethical dilemma. Two later known died, where one is Liberian doctor and a Spanish

Currently there is no ZMapp, the new batch upcoming need to go through some screen before it is officially launched. It may be tried again in future. The proper dose still remains unknown. The drug

co plants, and developed by US government support will take several months from now, as mentioned by ZMapp’s maker- Mapp Biopharmaceutical Inc., San Diego.

The deadly Ebola has killed more than 1,500 people in 2014 and World Health d that it may reach as many as 20,000cases before the outbreak

brought under control. There is no as such till now approved vaccine that can be treated against Ebola, but just supportive care is required. A recent research from the researchers of

etts claim that the Ebola virus is mutating rapidly, after screening initial patients in Sierra Leone with around 400 genetic modifications[4]. This may give a reZMapp manufacturers not working as a true vaccine. Efforts now been made to fincases and tracking their contacts to limit down the flow of the disease. Ebola spreads mostly via blood contacts and other body fluids. US Federal health officials start their human trials on Ebola vaccine as soon as it proves positive after testing on

ZMapp cures monkeys of Ebola virus. CBS News, August 29, 2014.What is the Ebola virus disease survival rate? Health News, www.healthsite.comEbola virus outbreak can hit 20,000 within nine months warns WHO. www.online.wsj.comEbola virus ‘is mutating rapidly’, expert warns. Mail Online, www.dailymail.co.uk

2014

Erica Ollmann Saphire at Scripps event showing a model of the Ebola surface protein antibodies attached. (AAAS News)

American aid workers, Nancy Writebolwho got infected with Ebola while working in Africa, were allowed

both recovered. Due to limited supply, five more infected recent weeks, the use of untested drug has incited

an ethical dilemma. Two later known died, where one is Liberian doctor and a Spanish

The deadly Ebola has killed more than 1,500 people in 2014 and World Health d that it may reach as many as 20,000cases before the outbreak

brought under control. There is no as such till now approved vaccine that can be treated against Ebola, but just supportive care is required. A recent research from the researchers of

etts claim that the Ebola virus is mutating rapidly, after screening initial patients in Sierra Leone with around 400 genetic modifications[4]. This may give a re-think for the ZMapp manufacturers not working as a true vaccine. Efforts now been made to find out the cases and tracking their contacts to limit down the flow of the disease. Ebola spreads mostly via blood contacts and other body fluids. US Federal health officials have announced to

ositive after testing on

www.healthsite.comwww.online.wsj.com

www.dailymail.co.uk


21

2014

Structure Based Viral Vaccine Design: A Changing Face of Vaccinology

R. Santhamani1, and I. Sophia2

Ph. D. scholar, Division of Virology1

Ph. D. scholar, Division of Bacteriology and Mycology2

Indian Veterinary Research Institute, Mukteswar, Nainital, Uttarakhand, India-263 138

Introduction

Currently in use conventional and new generation vaccines are preventing diseases

when the virus is antigenically stable and humoral immunity is protective. Approach for.

Structure based vaccine design is a method combining the structural biology and

bioinformatics to design vaccine, developed to combat highly antigenically variable viruses.

The protective epitope is identified using X-ray crystallography, nuclear magnetic

resonance spectroscopy or cryo-electron microscopy. The antibody binding amino acids in

the epitope is transplanted to the viral scaffold protein for stabilization of epitope and

immune presentation. The epitope scaffolds were evaluated for its folding and stability.

Structure based vaccine design is found promising for Respiratory Syncytial virus. This

approach could be applied to viruses like rotavirus, influenza virus, West Nile virus, equine

infectious anaemia virus, etc.

Vaccines-Past and Present Trend

Conventional vaccines like live attenuated and inactivated vaccines protect against

diseases when the disease is protected by humoral immunity and minimal antigenic

variation, Ex. peste-des petits ruminants virus, poliovirus, rinderpest virus. New generation

vaccines like subunit vaccines, gene deleted vaccines, recombinant vaccines, DNA

vaccines, and reverse vaccinology were developed to improve the safety and facilitating the


22

2014

DIVA (Differentiation of Infected and Vaccinated Animals) strategy. These vaccines are

failing when there is rapid and extensive antigenic variation, Ex. HIV, hepatitis C virus,

influenza virus, and exacerbation of diseases by immune response, Ex. RSV, dengue virus.

What is Structure based vaccine?

It is a brand new branch of vaccinology and uses epitope based approach. It involves

identification of antigenic protein sequence of interest by combining structural biology and

bioinformatics. It has been developed to combat vaccine failures in antigenically diverse

organisms.

Brief history

Scientists of Vaccine Research Center (VRC) at the U.S. National Institute of Allergy

and Infectious Diseases in Bethesda, Maryland (Jason McLellan, Barney Graham, and

colleagues) used structural biology to successfully engineer an immunogen. They isolated

potent neutralizing antibodies to RSV from infected people, but had failed to develop an

immunogen that could stimulate their production. The flexible F protein has two distinct

shapes, adopting one before fusion begins and one after it’s completed. It was achieved by

serendipity, for improved vaccine for respiratory syncytial virus (RSV). RSV causing child

& elderly morbidity and mortality in western countries. It also evade innate immunity, Ag

variability, vaccine enhanced disease, TH2 imbalance (Sullender et al., 2000). When they

eliminated antibodies that bound to postfusion F from the serum of people infected with

RSV, the leftover antibodies continued to neutralize the virus. That created a great

opportunity, there was another type of response that could be much better than the one to

postfusion F. They crystalized a potent antibody bound to the prefusion F structure and

identified the site on the virus that was especially vulnerable to neutralization. But the

prefusion protein was unstable, making it impossible to formulate as an immunogen. So the


team set out to effectively freeze the prefusion F structure, forcing it to continuously display

that vulnerable site. The team stabilized the F protein into the specific shape it wanted by

introducing new chemical bonds and swapping out naturally occurring amino acids for

substitutes that would fill cavities in its structure. The vaccine underwent mice and rhesus

monkey trials and proven successful in the 2013. Human clinical trials going on and it will

end by 2015 (McLellan et al., 2013).

Fig.1 Structure of F protein of respiratory syncytial virus

Determination structure of viruses

Before entering to structural vaccinology, virus structure determination is essential. There

are several methods to determine the structure of the viruses.

Microscope is commonly used conventional method to view the structure of viruses.

a. X-ray crystallography

It is working based on the principle of d

Angles and intensities of diffracted beam of X


23



new chemical bonds and swapping out naturally occurring amino acids for



end by 2015 (McLellan et al., 2013).

ig.1 Structure of F protein of respiratory syncytial virus

Determination structure of viruses


rmine the structure of the viruses. Transmission Electron


It is working based on the principle of diffraction of X-rays by crystallized specimen.

Angles and intensities of diffracted beam of X-rays used to create e

2014



new chemical bonds and swapping out naturally occurring amino acids for



ig.1 Structure of F protein of respiratory syncytial virus


Transmission Electron


rays by crystallized specimen.

rays used to create e- density map, with


24

2014

chemical information the atomic structure can be reconstructed. Eg. Virus, protein, nucleic

acid, drugs, etc. (Kulp and Schief, 2013).

Fig.2. X-ray crystallographic structure of Bluetonguevirus-1

b. Nuclear magnetic resonance spectroscopy

Epitope identification based on difference in mobility between aa residue of antigen

that interact with antibody and residues outside the epitope. Interacting antigenic peptide is

getting immobilized by antibody binding; the mobility resembles the antibody residue. To

resolve the structure using NMR macromolecule must be soluble and highly purified.

Methods have been developed for solid macromolecules also. Resolving power is lesser

than X-ray crystallography. Structure determined for small polypeptides less than 64 kDa.

c. Cryo-electron microscope

It is a form of transmission electron microscope wherein the samples studied at

cryogenic temperature. Biological material is spread on the electron microscopic grid and

rapid freezing in liquid ethane at temperature near liquid nitrogen has to be done. Then the

grid is introduced into the vacuum of electron microscopic column. Cryo-electron

microscopy can do 3D reconstruction with sub-nanometer resolution. Ex. Viruses,

proteins (Chang et al., 2012).


25

2014

Steps in structural Vaccinology

(Stamatatos et al., 2009)

Broadly Neutralizing Antibodies

They are antibodies which binds the highly conserved region of surface glycoprotein.

Broadly neutralizing antibodies are generated against influenza virus and HIV. Used in

passive immunotherapy for treatment of diseases caused by them. They are currently used

in universal vaccine design i.e. structure based vaccine design Eg. HA of influenza virus

and env of HIV has broadly neutralizing epitopes. Ex. 4E10, 2F5 abs target the gp41 and

p12, VRC01 targets the gp120 of HIV (Hafferson et al., 2014).


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2014

a. Identification of neutralizing epitope

The techniques which are used for determination of virus structure such as X-ray

crystallography, cryo-electron microscopy and NMR spectroscopy can be used for

determination of antibody binding amino acid residues. For example, in RSV F

moavizumab epitope is just 13 discontinuous amino acid residues. These 13 residues are

sufficient to elicit motavizumab like Ab provided with the 3D structure is maintained.

These 13 amino acids found as 2 alpha-helices (two segment epitope) (McLellan et al.,

2010).

Fig.3. Two-segment motavizumab epitope of respiratory syncytial virus

b. Design of epitope scaffold

i. Side chain grafting method

It is used for single segment epitope design. The epitope segment is searched in

protein data bank (PDB) for structural match. Sequence independent structural matches

selected based on Rmsd (<1.5A0). Rmsd values indicate backbone similarity. E.g. 4E10


27

2014

epitope of HIV is single segment epitope (Correia et al., 2010, Kwong et al., 2011 and

Pejchal and Wilson, 201).

ii. Two segment side chain grafting method

When a match for one segment is found, that scaffold was searched second time for

structural similarity to the other epitope segment. Eg. RSV F motavizumab epitope is two

sgment epitope (Ofek et al., 2010).The demerits of side chain grafting method are that the

scaffolds with backbone of similar 3D structure to epitope are needed. Also in this method

the epitope conformation was found to differ slightly and as a result it reduces affinity of

Ab-epitope scaffold interaction (Azoitei et al., 2012). To overcome these disadvantages

backbone grafting method was developed.

iii. Transplantation of epitope side chains to the scaffold

In the design stage, epitope side chains were transplanted to the appropriate positions on

the scaffolds, and further mutations were designed on each scaffold to minimize non

epitope interactions with antibody and to optimize stability. Rosetta Design was used to

pack side chains on the scaffold backbone, with side-chain conformations restricted to those

contained in the backbone-dependent rotamer or to native scaffold rotamer conformations.

Antibody-contacting epitope residues [gp41 4E10 epitope (E659, L661, E662, D664, K665,

W666, A667, L669)] were transplanted to corresponding scaffold positions according to the

MAMMOTH structural alignment, while scaffold positions adjacent to the epitope or to the

antibody were designed to accommodate epitope side chains and avoid interactions with

antibody, and all other scaffold positions were assigned native scaffold amino-acid

rotamers. Also eliminate unpaired cysteines and trim scaffold termini to avoid clash with

antibody. Scaffolds checked for antibody clash using Rosetta Design (Correia et al., 2010).

For influenza virus structure based NS1 mutant developed (Akarsu et al., 2011). This

approach can be applied to develop subtype specific structural vaccine for influenza virus

(Xuan et al., 2011).


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2014

iv. Backbone grafting method

It is a computational protocol for grafting linear functional motifs (epitope). Rather

than transplanting the side chains of a functional motif onto a pre-existing scaffold

backbone, backbone grafting replaces the native backbone of a candidate scaffold with the

desired backbone conformation of a functional motif (epitope). Thus, epitope backbone

grafting imposes the conformation of a given epitope onto a scaffold and integrates that

epitope conformation into the scaffold through backbone remodeling and sequence design

in regions flanking the epitope. It improves the binding affinity between epitope scaffold

and antibody and it is used for linear epitopes (Azoitei et al., 2012).

Fig.4. Side-chain and backbone grafting methods

v. Production of epitope scaffold

DNA sequence encoding epitope-scaffold is synthesized chemically with codon

optimization. Then it is cloned into bacterial/mammalian expression vector and expressed.

Purified using Ni-NTA, Strep-Tactin, column chromatography and anion exchange

chromatography (McLellan et al., 2010).


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vi. Evaluation of epitope scaffold

Property analysed Technique Principle

Binding of epitope scaffold

to bNAb and binding

affinities of bNAb

Surface plasmon

resonance

Fab of antibody coupled to detector

chip and epitope scaffolds flowed

Thermodynamics of Ag-Ab Isothermal titration

calorimetry

Epitope scaffold titrated with IgG

(Entropically / enthalpically driven)

Thermal stability and

proper folding

Circular dichroism

spectroscopy

Measures the differential absorption

of light- protein secondary structure

Atomic-level mimicry of the

epitope

X-ray crystallography Epitope scaffold with specific Ab

Immunogenicity

(AS01B/Alum+CpG)

Mice/guinea pig/Rabbit

immunizations

In-vivo immune response

Serum Ab binding to

scaffold/ whole immunogenic

protein

Peptide ELISA Indirect format

Determination of the

binding specificity of Ab

Epitope scaffold

competitive ELISA

Scaffold inhibits the sera from

neutralizing r-viral protein

Advantages

• If immunogenic protein has immunosuppressive sequence, it can be trimmed off from

the immunodominant epitope and designed a vaccine

• Safer and easier to produce

• Prevention and treatment of pathogenic diseases, cancers and autoimmune diseases

• Easy distribution, low cost and stably stored


30

2014

• If epitope is exposed transiently, it can be used for vaccine design (McLellan et al.,

2010).

Conclusions

Structural vaccinology implies that the single epitope could induce protective Ab. Structural

biology and bioinformatics softwares are used in this approach. It is promising for the

viruses dodging the immune system and highly variable viruses like HIV, influenza virus,

hepatitis C virus. It is a cheap and safe method of vaccine design. Currently there is no

structure based vaccines are commercially available.

Future perspectives

• Frequency of dosing, dose, route, adjuvant, duration and magnitude of immune

response to be optimized for RSV

• Studies on structural basis for Ag processing may lead to structural vaccine design

to elicit T cell mediated immunity

• Determination of broadly neutralizing epitopes or immunodominant epitopes for

various viruses using X-ray crystallography and cryo-electron microscopy is

necessary to take a step into structural vaccinology

• Design of universal vaccine (for viruses of entire subtype) for antigenically variable

influenza virus

• Animal virus vaccines for antigenically variable viruses may be developed based on

this approach, provided with the virus has conserved epitope across the strains. Eg.

bluetongue virus, rotavirus, influenza virus, etc.

• Role in Differentiation of Infected and Vaccinated Animals (DIVA) strategy in

veterinary medicine

• Humoral and cell mediated immune responses induction

• Inclusion of multiple epitopes to improve immune response

• Further atomic level studies may prove success in HIV vaccine


31

2014

ReferencesAkarsu, H., Iwatsuki-Horimoto, K., Noda, T., Kawakami, E., Katsura, H., Baudin, F., Horimoto, T., Kawaoka, Y. (2011).

Structure-based design of NS2 mutants for attenuated influenza A virus vaccines. Virus Research, 155(1), 240–248.

Azoitei, M.L., Yih-En, A.B., Julien, J.P., Bryson, S., Schroeter, A., Kalyuzhniy, O., Porter, J.P., Adachi, Y., Baker, D., Pai,

E.F. and Schief, W.R. (2012). Computational Design of High-Affinity Epitope Scaffolds by Backbone Grafting of a Linear

Epitope, Journal of Molecular Biology, 415, 175–192.

Chang, J., Liu, X., Rochat, R. H., Baker, M. L. and Chiu, X. (2012). Reconstructing Virus Structures from Nanometer to

Near-Atomic Resolutions with Cryo-Electron Microscopy and Tomography. Advances in Experimental Medicine and

Biology, 726, 49-90.

Correia, B. E., Ban, Y. E. A., Holmes, M.A., Xu, H., Ellingson, K., Kraft, Z., Carrico, C., Boni, E., Sather, D. N., Zenobia,

C., Burke, K. Y., Bradley-Hewitt, T., Bruhn-Johannsen, J. F., Kalyuzhniy, O., et al. (2010). Computational Design of

Epitope-Scaffolds Allows Induction of Antibodies Specific for a Poorly Immunogenic HIV Vaccine Epitope. Structure, 18,

1116–1126.

Hefferon, K. L. (2014). Broadly Neutralizing Antibodies and the Promise of Universal Vaccines Where Are We Now.

Immunotherapy, 6(1), 51-57.

Kulp, D. W. and Schief, W. R. (2013). Advances in structure-based vaccine design. Current Opinion in Virology, 3(3), 322-

31.

Kwong, P. D., Mascola, J. R., Nabel, G. J. (2011). Rational design of vaccines to elicit broadly neutralizing antibodies

against HIV-1. Cold Spring Harbor Perspectives, doi: 10.1101/cshperspect.a007278.

McLellan, J. S., Chen, M., Kim, A., Yang, Y., Graham, B. S., Kwong, P. D. (2010). Structural basis of respiratory syncytial

virus neutralization by motavizumab. Nature Structural and Molecular Biology, 17, 248–50.

McLellan, J. S., Chen, M., Joyce, M. G., Sastry, M., Stewart-Jones, G. B., Yang, Y., Zhang, B., Chen, L., Srivatsan, S., et al.

(2013). Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science, 342(6158), 592–

598.

Ofek, G., Guenaga, F. J., Schief, W. R., Skinner, J., Baker, D., Wyatt, R., Kwong, P. D. (2010). Elicitation of structure-

specific antibodies by epitope scaffolds. Proceedings of the National Academy of Sciences, 107, 17880–7.

Pejchal, R. and Wilson, I. A. (2010). Structure-based vaccine design in HIV: blind men and the elephant?. Current

Pharmaceutical Design, 16(33), 3744–3753.

Stamatatos, L., Morris, L., Burton, D. R., Mascola, J. R. (2009). Neutralizing antibodies generated during natural HIV-1

infection: good news for an HIV-1 vaccine. Nature Medicine, doi:10.1038/nm.1949

Thomas, S. and Luxon, B. (2013). Vaccines based on structure-based design provide protection against infectious diseases.

Expert Review of Vaccines, 12 (11), 1301-1311.

Xuan, C., Shi, Y., Qi, J., Zhang, W., Xiao, H., Gao, G.F. (2011). Structural vaccinology: structure-based design of influenza

A virus hemagglutinin subtype-specific subunit vaccines Protein. Cell, 2(12), 997–1005.


Dr. Robert A. Edwards, Bioinformatics Professor, SDSU.

Novel Virus: crAssphage discovered in half the world’s population

Department of Human Genetics, Institute of Life Sciences, Bhubaneswar, India

A recent paper published in Nature communicationsfrom San Diego State University (SDSU) found that more than a half of world’s population has been a host of a new discovered virus, named crAssphage. This virus infects most of the

Dutilh used previous studies on gutpresent.

The Research

Using 12 individual faecal samples, found a particular cluster of viral DNA, which is about 97000 base pairs long and samples all have common. When this result came in front, Edwards and his colleagues were surprised and were in mere shock.The researchers then screen the viral DNA across the database of National Institute of Health’s Human Microbiome Project (HRAST database and found again in abundance in faecal samples.


32

Robert A. Edwards, Bioinformatics

crAssphage discovered in half the world’s population

Saumyadip SarkarDepartment of Human Genetics, Institute of Life Sciences, Bhubaneswar, India

[email protected]

Nature communications, where a new study led by researchers from San Diego State University (SDSU) found that more than a half of world’s population has been a host of a new discovered virus, named crAssphage. This virus infects most of the

common type of gut bacteria, BacteroEarlier researches have revealed that this bacteria is thought to be connected with and associated gut-related diseases, but now it may prove to be uncertain after this accident discovery.Bioinformatics professor at SDSU, Dr. Robert A. Edwards along with his colleagues stumbled with this accident discovery. While working with a visiting researcher from Radboud University

Medical Center in Netherlands and the corresponding author of the research, Dr. Bas E.

Dutilh used previous studies on gut-inhabiting viruses to curve out the novel viruses might

Using 12 individual faecal samples, found a particular cluster of viral DNA, which is about long and samples all have common. When this result came in front,

Edwards and his colleagues were surprised and were in mere shock.The researchers then screen the viral DNA across the database of National Institute of Health’s Human Microbiome Project (HMP) and Argonne National RAST database and found again in abundance in faecal samples.

2014

crAssphage discovered in

Department of Human Genetics, Institute of Life Sciences, Bhubaneswar, India

, where a new study led by researchers from San Diego State University (SDSU) found that more than a half of world’s population has been a host of a new discovered virus, named crAssphage. This virus infects most of the

common type of gut bacteria, Bacteroidetes. Earlier researches have revealed that this bacteria is thought to be connected with obesity, diabetes

related diseases, but now it may prove to be uncertain after this accident

Bioinformatics professor at SDSU, Dr. Robert A. Edwards along with his colleagues stumbled with this accident discovery. While working with a visiting researcher from Radboud University

Medical Center in Netherlands and the uthor of the research, Dr. Bas E.

inhabiting viruses to curve out the novel viruses might

Using 12 individual faecal samples, found a particular cluster of viral DNA, which is about long and samples all have common. When this result came in front,

The researchers then screen the viral DNA across the database of National Institute of MP) and Argonne National Laboratory’s MG-


33

2014

To come out from the dry lab discovery, they actually wanted to prove that this virus does actually exist, hence Edward hand on this news to Dr. John Mokili, SDSU virologist, where he used DNA amplification technique to locate the virus in the original samples used in NIH’s database. The proof was found and this has become an accident discovery. The virus that has been present in most of the people in their bodies and no one knows about it.

“It’s not unusual to go looking for a novel virus and find one,” Edwards said. “But it’s very unusual to find one that so many people have in common. The fact that it’s flown under the radar for so long is very strange.”

History behind this Virus

The fact behind this virus to be found in most of the people in the world, gives a punch that this virus is not young. It is found to be present in all different kinds of population and it may be as old as humans are.The proteins of crAssphage’s DNA are much common to those found in other well known viruses. The DNA size is almost ten times longer than that of HIV’s. The method of infecting Bacteroidetes is quite like bacteriophage.Bacteroidetes bacteria present at the end of the intestinal tract and have found to be the suspect of obesity. The role of this crAssphage in this process would be a target of the future research. It is lot to know about this virus. It is interesting to know that this virus is not found in young infants’ faecal samples and thus it may be transmitted maternally. The make of the DNA is circular in structure, a singular entity and had been difficult for the researcher to isolate. The potential role behind the crAssphage with Bacteroidetes with obesity is yet to discover. Hope for a personalized medicine to come up soon.

Study Source:1. Novel Virus Discovered in Half the World’s population. Microbe World.

http://www.microbeworld.org/component/jlibrary/?view=article&id=12671

Reference:1. Novel Virus Discovered in Half the World's Population. Research, Innovation and Discovery, San

Diego State University News bulletin.http://newscenter.sdsu.edu/sdsu_newscenter/news.aspx?s=75082

2. Video Source: https://www.youtube.com/watch?v=HOMoiSFmkxsDutilh, B.E., Cassman, N., McNair, K., Sanchez, S.E., Silva, G.G.Z., Boling, L.L., Barr, J.J., Speth, D.R., Seguritan, V., Aziz, R.K., Felts, B., Dinsdale, E.A., Mokili, J.L., Edwards, R.A., 2014. A highly abundant bacteriophage discovered in the unknown sequences of human faecal metagenomes. Nature Communications, doi:10.1038/ncomms5498.


PORTRAITA talk with

Environmental Microbiology Laboratory

Indian Institute of Technology (IIT)

MW: Balaram Mahapatra,

motivation towards the field of Microbiology we would wish to know li

of introduction you would wish to give

Mr. Mahapatra: First of all I am very thankful to WTM team for providing me su

opportunity to share my thoughts. Yes I feel very proud that I am a student of a premier

institution of India, IIT-KGP. I am really very lucky that I have been assigned with the

work that actually means a lot to the society and its benefit. I have been

(As) contamination in the groundwater system of West Bengal, which is also a major


34

PORTRAITA talk with Balaram Mahapatra

Ph.D research ScholarEnvironmental Microbiology Laboratory

Department of BiotechnologyIndian Institute of Technology (IIT) - Kharagpur, India

, an IITan research scholar, and based on the

otivation towards the field of Microbiology we would wish to know li

ntroduction you would wish to give us?

First of all I am very thankful to WTM team for providing me su


KGP. I am really very lucky that I have been assigned with the

work that actually means a lot to the society and its benefit. I have been


2014

Balaram Mahapatra

based on the research

otivation towards the field of Microbiology we would wish to know little background

First of all I am very thankful to WTM team for providing me such


KGP. I am really very lucky that I have been assigned with the

work that actually means a lot to the society and its benefit. I have been working on Arsenic



35

2014

problem of many countries of the world, its microbiological aspect of As homeostasis and

targeting to develop suitable remediation technology. As I have been graduated with

agricultural microbiology, by associated with many of the research scholars of different

department of this institution, I am also working on setting up biogas plants in nearby

villages of IIT-KGP and its maintenance to get fuel for the farmers and villagers. Recently

our team is focusing on making vermin-compost and composting units in different villages

to have productive agriculture for the households. I am sure that I will be working on these

areas sincerely to have an effective and beneficial research output for the country.

MW: Starting from your early school life, how was your study background? Which

subject intimated you the most?

Mr. Mahapatra: My schooling was from B.S.S.P. Vidyamandir, Puri, Odisha, a school

of Board of Secondary Education (BSE), Odisha, India. From my early school life, I was

very much curious to know the processes in living organisms, how they perform different

activity, what is the root cause and driving force of the cellular process, mostly in plants. In

school and intermediate level, I was the topper of my school and college. After completing

my +2 Science from S.C.S College under CHSE board, Odisha I was quite uninterested for

engineering career and I was admitted into Bachelor degree in Science (Graduation) with

Botany as my honours subject in the same College under Utkal University. During the time

of my graduation, plant physiology and plant-microbe interaction intimated me the most. I

became the 1st rank holder of my college and also awarded with JBNSTS fellowship. I

cleared entrance examinations of different university across Odisha to get seat in life

science/ Microbiology master’s progamme and finally got admitted to M.Sc in

Microbiology at Orissa University of Agriculture and Technology (OUAT-ICAR),

Bhubaneswar. During my M.Sc carrer, I had good research experiences by working on

Microbial antagonism of Lactic Acid Bacteria (LAB) on enteric pathogen, Plant Growth

Promoting Rhizobacteria (PGPR) and microbial lipases (alkaline and cold active lipases) at


36

2014

different research institutes and my own university. I also got 1st rank in M.Sc microbiology

and have been awarded with DST-INSPIRE fellowship and cleared NET and GATE

examinations for getting entry into doctoral research. Finally settled here at IIT-Kharagpur,

India, working for a safer environment.

MW: After you passed your graduation with Microbiology as your degree course, in

what way your motivations evolve to go for research?

Mr. Mahapatra: I have been graduated in Botany (plant science) from Utkal University,

Odisha. During my study years, plant physiology, microbial interaction with plant root in

soil and their two way cross talk for plant health and disease management were interesting

subjects. I used to explore different plant types in varied soil collected from various parts of

puri and nearby places and was trying to find out the microbial structures and their

association on plant root/stem surfaces, the metabolic potential of those microbes in soil

microhabitat and bioactive property of those tiny creatures. During my graduation, I also

studied the beneficial properties of different medicinal plants and their disease healing

property. For studying deeper microbiological aspects, my teachers motivated a lot and I am

really thankful to them who guided me to go for higher research carrier in OUAT and IIT-

KGP.

MW: You have been into writing research articles in multiple journals and magazines.

How you feel that communicating research is important among the public of varied

nations?

Mr. Mahapatra: As I am a Ph.D scholar, I am very fascinated to write many research

articles for multiple journals and magazines because I think scientific findings in research is

incomplete until it is shared in the scientific as well as public domain for the scientists who

can make further advancement and also for the common man who can have benefit from it.


37

2014

The prime objective of the science is to eradicate ignorance through knowledge and to work

for a better world, research among scientific community needs to be preached among the

whole public of the world, as the whole world is one family, “��

��” and it also brings fame, glory, joy and success.

MW: Going little back towards your family background, how your parents and

teachers motivate you to go for research?

Mr. Mahapatra: I have family of four members, with my father, mother, me and my

little sister. As my mother is a science graduate, she used to motivate me from my

childhood by teaching me different fundamental aspects of science. During my schooling

carrier, with help of my mother and teachers, I used to do science projects in district and

state level science exhibitions and has been awarded many times for my projects like cost

effective use of wastewater in agriculture, solar heater, low cost water filtration unit using

traditional methods, biogas plant, composting etc. My father is having business and he

supported my education without any hesitation and gives me immense motivation to do

research for helping my society and nation.

MW: What your current focus of research you are carrying out in Indian Institute of

Technology, Kharagpur, India? Will you wish to share your ideas how your research

can be useful for the future society?

Mr. Mahapatra: At IIT-Kharagpur, Department of Biotechnology, under Supervision of

Dr. Pinaki Sar, my research has been focused in the field of environmental microbiology

and biotechnology. Groundwater is known to be the primary drinking water resources for

public and contamination in this system can bring severe health hazards. Declared by WHO,

arsenic (As) known to be a carcinogen and highly toxic for living forms and its

contamination in groundwater leads to threats, affecting millions of people worldwide. Role


38

2014

of indigenous bacteria of transforming this toxic metal and its homeostasis is of immense

importance to gain insight into the biogeochemical cycling, mobilization and degree of

toxicity in the water system. So, I am working on functional characterization and cellular

response of the bacterial isolates for understanding the bacterial metabolism that could

affect biogeochemical cycling of As and its remediation form groundwater systems.

MW: Do you feel India has got brighter future in Microbiological Research including

the fields of Life Sciences?

Mr. Mahapatra: Absolutely yes. As rightly said by Sir Einstein that, “Imagination is

powerful than knowledge”, there are immense scope of developing new ideas and

technology in this field due to its versatility of having impact in field of medical,

agriculture, industrial, environmental, dairy, pharmaceutical, nanoscience, natural

resources. As we know, only about 1% of the microbial diversity is culturable and many are

unexplored and also India is known to be the land of six bio-geographic regions, there are

wide and great opportunities for the future microbiologists to unravel the mystery of new

microbial life on the planet as well as outside of it, discovering new bioactive metabolites

for benefit of human society. At this time, what is needed is power of thinking to create

new, innovate and to be a smart entrepreneur in the field of microbiology not just for

livelihood but for the sake of welfare of the world.

MW: The obvious question does arise, what is your future plan after completing your

doctorate in philosophy in Microbiology?

Mr. Mahapatra: After my Doctorate degree, I want to join in the field of higher

research in basic science as a research scientist. But I feel, doing research only should not

be the ultimate motto and if the scientific output/innovation/technology can’t reach to the

common people, then it is worthless. So, I want to be an entrepreneur, open my own


39

2014

industry of biofertilizer/waste water treatment and bring the innovation to the public for

their benefit.

MW: Being the young researcher of India, what would you advice to Indian Students

about the current research background of India as well as in developing countries?

Does going for research is safer carrier?

Mr. Mahapatra: Research in Indian scenario, is in peak as India is one of the rapidly

progressing country in the field of basic science research. Research is one of the

fundamental tools for country’s growth, development and economy. So, the students with

best academic credentials should prefer research as their carrier and contribute their

knowledge to the society. India’s economy is dependent on agriculture and it is also

required to solve the food problem of the country and hence rushing minds into agricultural

research can benefit more to the society. Along with it, research in pharmaceutical, medical,

environmental issues, space science etc is on demand. Obviously, going for research is not

only safe but also needed for this country. In current times, government funding agencies

like DST, DBT, CSIR, DSIR etc are opening up with new schemes, new agendas with

special emphasis on viable research and innovation systems. Now India is also getting

connected to global research councils of many countries creating a lot scope for future

comer in this field.

MW: Provide your suggestions to the upcoming generations, how to prepare for the

various entrance examinations to make them involve into Ph.D.

Mr. Mahapatra: Ph.D, the highest academic degree in any science can enable a person

to think about his/her country by contributing scientific research. In India, various

examinations are being conducted by many funding agencies like CSIR, DBT, UGC, ICAR,

ICMR as NET (national eligibility test), combined entrances by JNU, BHU, IISC, TIFR etc


40

2014

and GATE for getting entry into IITs and NITs. Thorough study of basic science in the

grass root from graduation level is the fundamental requirement. Problem solving and

aptitude based approach can help students very much. Basics fundamentals books can help

in this regard. Research background of students in master degree help a lot for getting

chance to do Ph.D in foreign countries. GRE, TOEFL exams and good publications with

some research experiences is the basic criteria for getting selected in foreign Ph.D

programme. During the Ph.D carrier also one can avail any foreign fellowship (doctoral

fellowship programme like- Nehru and Mobility fellowship) and work at good reputed

universities.

MW: A short note on We The Microbiologist

Mr. Mahapatra: I feel proud being the part of WTM, India. Recently there is need of

bringing awareness to the graduate and undergraduate students regarding scientific research

throughout the world, the carrier ahead in it. WTM is doing it in proper way, gathering

scientific minds, communicating the science within the students and researchers in the

world - A social awareness and service. Hope, it will definitely accommodate more and

more researchers from different background for a better service to the society.

All the very best to the team- WTM.

*******************


Opportunities

PhD position opportunities

EMBL International PhD Programme 2015

Application for the Spring Recruitment 2015 is now open.

Information to the applicants

recruitment process (application, interview meeting, processing, training or any other fees).

The EMBL does not concern itself with information on bank accounts.

Application opend: 04 August 2014

Registration Deadline: 03 November 2014, 23:59 CET (GMT+1), via online application

form.

Application Deadline: 10November 2014, 23:59 CET (GMT+1)

Reference Deadline: 12 November 2014, 23:59 CET (GMT+1)

Detailed Information is available at:

Project Title

Funding

Funding for this studentship is available to both UK/EU and International students. We are

looking for a motivated and ambitious PhD student to help address these important research

questions. Applicants will be shortlisted for interview based on their academic credentials

and are expected to have a First Class Honours undergraduate degree and/or an excellent

postgraduate qualification. Deadline:

Detailed Information is available at:

lectins-606.php


41

Opportunities

PhD position opportunities

EMBL International PhD Programme 2015


Information to the applicants: The EMBL does not charge a fee at any stage of the


concern itself with information on bank accounts.

04 August 2014

: 03 November 2014, 23:59 CET (GMT+1), via online application

: 10November 2014, 23:59 CET (GMT+1)

ember 2014, 23:59 CET (GMT+1)

Detailed Information is available at: http://www.embl.de/training/eipp/application/

Project Title: The Role of C-Type Lectins in Anti-

Funding opportunities: Funded by the University of Aberdeen.



will be shortlisted for interview based on their academic credentials


Deadline: 15 October 2014

Detailed Information is available at: http://www.abdn.ac.uk/clsm/graduate/research/ctype

2014


The EMBL does not charge a fee at any stage of the


: 03 November 2014, 23:59 CET (GMT+1), via online application

http://www.embl.de/training/eipp/application/

-Fungal Immunity

Funded by the University of Aberdeen.



will be shortlisted for interview based on their academic credentials


http://www.abdn.ac.uk/clsm/graduate/research/ctype-


42

2014

International PhD Programme in Life Sciences

The Life Science Zurich Graduate School consists of several

highly competitive Ph.D. programs, run jointly by the ETH

Zurich and the University of Zurich. Each program offers research and education

opportunities in a stimulating international environment for ambitious students who wish to

work towards a Ph.D. degree. Accepted students are fully funded (ca. EUR 34'500 p.a.) and

perform their research project in one of the participating research groups of their favorite

program, according to their scientific interest. Advanced teaching and training courses are

offered throughout the curriculum. The program language is English throughout. Ph.D.

studies usually last 3-4 years.

Our web pages provide detailed information for submission of application. Please refer to

the guidelines as we only take into consideration applications received in the required

format:

www.lifescience-graduateschool.ch/application.html

Application deadlines are July 1 and December 1

NB: Information provided here are not for advertising the universities rather to highlight the

opportunities to provide the extent of research in the field of Microbiology and Life

Sciences.

For submission of articles in Micrographia Today visit: www.micrographiatoday.org

Editor in Chief: [email protected]

Contact e-mail: [email protected]

Supported by We The Microbiologist, India: www.wethemicrobiologist.in

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