India Alliance Newsletter I Issue 5 I September 2015

News & Views Issue 5, September 2015

INDIA ALLIANCE

EDITORIAL

As we bring out this September issue, our Science Communication workshop mentors, Drs Lolitika Mandal, Mahak Sharma, Anant Bhan, Anurag Agrawal and Prof Sandhya Visweswariah conclude the 12th two-day workshop in Hyderabad.

We do not have any updates on the Fellowship front as currently all our fellowship competitions are closed and the submitted applications are under review. In this newsletter, some of our Research Training Fellows write about why they chose to pursue a career in clinical research and how the IA Fellowship scheme will be helpful going forward. In our Public Engagement section, we give you an account of our recently concluded DNA@70 Public Lecture Series and announcement for our newly launched „Research Image competition‟ for Fellows. Even though the Monsoon season passed away quietly, our Fellows made sure it rained publications. In this issue, we also feature recently published works of our Fellows Drs Bushra Ateeq, Sunish Kumar Radhakrishnan, Rakesh Kumar Laishram, Amit Dutt and Subba Rao Gangi Setty in the „IA Research Highlights‟ section.

In this issue, the feature article “Peeking inside the HIV infected cells” by our Senior Fellow, Dr Amit Singh, provides an insightful overview of the research strategies for HIV and TB eradication in the context of his current research. Early Career Fellows, Drs Megha and Neha Vyas address the elephant in the room. They pose important questions about the future of postdocs to the scientific community in India in their opinion piece titled “Early Career Fellow: What next?”. Dr Shital Sarah Ahaley, our Early Career Fellow at IISER Pune, gives an interesting account of the EMBO Lab management course she attended in Germany which helped her to understand the subtle difference between management and leadership and reinforced the importance of scientific leadership for a successful research career, in a report titled “ Leadership and Management: two sides of the same coin?”. In our interview section, we bring to you a very candid and engaging interview of one our Public Lecture speakers, Dr Ajit Varki, who is a distinguished professor of medicine and cellular and molecular medicine, and co-director of the Glycobiology Research and Training Center at University of California, San Diego, USA. Our Early Career Fellow and newly appointed Assistant Professor at NIMHANS, Dr Urvakhsh Mehta, shares with us what inspired him to transition from being an MD to a clinician researcher and what keeps him going every day in the „Fellow in the Spotlight‟ section. Last but not the least, our Grants Adviser, Dr Suveera Dhup, reminisces about her childhood days and tells us why it has been fun to work at the India Alliance in „IA Staff Corner‟. Also, don‟t forget to check the announcements for Clinical training workshop organised by George Institute and Young Investigator meeting 2016.

My heartfelt gratitude goes out to all the contributors for this issue. A special thanks to Dr Subba Rao Gangi Setty for sharing a lovely image for the cover.

We will continue to bring to you interesting scientific discoveries and discussions and as always look forward to your comments and suggestions.

Best wishes, Sarah Iqbal Public Engagement Officer

1.

CONTENTS

3 5 7

RESEARCH TRAINING FELLOWS INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER Conclusion of DNA@70 Public Lecture Series- a report INDIA ALLIANCE RESEARCH HIGHLIGHTS Featuring recent research articles by Fellows, Drs Bushra Ateeq, Sunish Kumar Radhakrishnan, Rakesh K Laishram, Amit Dutt, & Subba Rao Gangi Setty

11

INDIA ALLIANCE FELLOW IN SPOTLIGHT Dr Urvakhsh Mehta, Early Career Fellow, NIMHANS Bangalore

13 FEATURE ARTICLE “Peeking into the HIV infected cells”

by Dr Amit Singh, Intermediate Fellow, IISc Bangalore

15 IN CONVERSATION WITH..

Dr Ajit Varki, distinguished professor of medicine and cellular and molecular medicine and co-director of the Glycobiology Research and Training Center at UCSD

17 VIEWPOINT

“Early Career Fellow: What next?”

by Drs Megha and Neha Vyas, Early Career Fellows at NCBS and inStem Bangalore, respectively

19 WORKSHOP

“Leadership and management: two sides of the same coin?”

by Dr Shital Sarah Ahaley, Early Career Fellows, IISER Pune

20 INDIA ALLIANCE STAFF CORNER Dr Suveera Dhup, Grants Adviser, India Alliance

21 EXTERNAL EVENTS

2.

INDIA ALLIANCE

RESEARCH TRAINING FELLOWS

More information on the India Alliance Clinical and Public Health Fellowships can be found at http://wellcomedbt.org/fellowshiptype/clinicaland-public-health-research-fellowships

Clinical and Public Health Research Fellowships The Wellcome Trust/DBT India Alliance’s two-year Research Training Fellowship was launched in 2014 and is a first-of-its-kind programme for clinicians in India. This mentored programme is unique in terms of the expectations it has set out for the structure of the training programme and involvement it demands from the research supervisors. The provision to get trained under the dual supervision of a clinical and a basic science researcher, and the flexibility to attend courses/workshops, allows Clinicians and Allied Health professionals to receive systematic training in research methodology. Some of the awarded Fellows from the first round of these Fellowships share their views on this Fellowship and how it will help them in the career paths they have chosen to pursue.

Click on their images to find out more about their current research projects.

clinical problem to lab. Mazumdar Shaw medical Center

Dr Muralidhara Nagarjuna

sports a dedicated state-of-the-art research lab facility with numerous research projects currently underway. Professor

Mazumdar Shaw Center for Translational Research, Bangalore

Dr. Paul C. Salins, the Chief of Cranio-Maxillofacial Services and Medical Director of the hospital, encouraged me to take up basic science research in this field. Dr. Aditya Chaubey, the Chief Scientific Officer of Mazumdar Shaw

Aiming at a surgical career, I was fortunate enough to

Centre for Translational Research, who has been working

get into post-graduation in the subject of Oral and

extensively in the field of stem cells and has already

Maxillofacial Surgery at one of the premier institutes in India.

developed excellent in vivo models for bone regeneration

SDM college of Dental Sciences is the first institute in India to

and scaffold designing, accepted to guide me in starting a

have a dedicated Craniofacial Surgery unit performing over

research career. I feel this research training fellowship will

1500 surgeries every year. The patient problems included but

allow me to dedicate my time in this exciting field and may

not restricted to oro-facial clefts, trauma, head and neck

in fact allow me to pursue a translational research career in

oncology, facial esthetic surgeries and infections. Facial

the future. Though inexperienced, I believe that undertaking

trauma remains one of the most common procedures

this fellowship at an early stage of my career will help me in

performed by the maxillofacial surgeons. Joining Mazumdar

better understanding of the existing clinical problems and

Shaw Medical Center, as a fellow in Cranio-Maxillofacial

developing a scientific problem solving attitude and apply

Surgery, provided me the necessary niche to take this

the newly acquired skills in patient care.

Benegal. During this time I also trained myself in advanced neuro-imaging analysis under the expertise of Dr G.

Dr Bharat Holla

Venkatasubramanian.

NIMHANS, Bangalore

Now I want to pursue a career of a clinician scientist and train myself in basic science. I have been fortunate that Dr Ravi Muddashetty has kindly agreed to train me at molecular genetics laboratory at inStem, NCBS under this fellowship.

Training in the prestigious Bangalore Medical College and

Currently I am also pursuing PhD in Psychiatry at NIMHANS.

Research Institute gave me a strong foundation in clinical

During this proposed research I wish to further elucidate the

medicine. I stood 1st for the state in the UG Medical Karnataka

biopsychosocial vulnerabilities for substance misuse in alcohol

Common Entrance Test. Right from the early days of MBBS, I

naive children from multiplex alcohol-dependence families

was fascinated by a career in a field that involves treatment

using Imaging-genomics approach.

and research of neuropsychiatric disorders. I consider myself

The RTF has provided the right platform for a young

privileged to have obtained MD Psychiatry at NIMHANS which

clinician like me. I hope to continue with translational research

is a premiere multidisciplinary academic, research and health

and clinical work as an independent investigator the field of

care institute in Brain - Mind - Behaviour Axis in India. I

neuroimaging and psychiatric genetics with expertise in

developed a keen interest in addiction psychiatry and did my

alcoholism.

MD thesis dissertation and also a post-doctoral addiction psychiatry clinical fellowship under the guidance of Dr Vivek

3.

The Wellcome Trust/DBT India Alliance

RESEARCH TRAINING FELLOWS

studying the molecular aspects of the disease. Realising the need to tie up with a molecular biologist, I now work in Dr.

Dr Maria Frances Bukelo

Sudhir Krishna‟s lab at the National Institute of Biological

St John’s Medical College, Bangalore

Sciences where I am learning the various molecular principles and techniques to carry out the proposed research.

My pursuit to learn and implement molecular biology in Medicine took me to the Molecular Medicine unit head at

Medicine was an automatic career choice for me as no

St. John‟s who told me that in order to fulfill my quest I need

other profession can boast of doing social good while

3 things; 1. an interest to learn molecular biology, 2.

challenging one academically, and giving one a sense of

adequate time to learn (1 hour per day after clinical work

purpose. The choice of specializing in pathology was

would not suffice) and 3. the financial resource to access

spontaneous, for apart from providing answers to my curious

these techniques. As a pathologist my interest in molecular

questions on the why‟s and how‟s of most diseases, it is a

biology stemmed from the calling to go beyond

subject so full of color and at times so full of instant satisfaction

morphological diagnosis to understanding the projections of

besides providing scope for teaching and research, which I

molecular alterations that drive disease into the realm of

wish to be very actively involved in.

morphology. And although morphological diagnosis is

The research projects I have taken up so far (through

challenging in itself, I wanted to use my two-dimensional

MBBS, Internship and MD thesis) have given me a small glimpse

morphological view of disease as a gateway to understand

into the world of research and have motivated me enough to

the three (and higher) dimensional molecular world of

want to pursue a research based approach in my practice of

disease, much of which may appear difficult to interpret but

Pathology. With this background, after completing my MD

never the less is the need of the hour to provide

studies, joining St. John‟s as Lecturer of Pathology in 2013 was

personalized therapies to our patients. It was along this track

an instinctive decision for apart from the pleasant work

that I came across this India Alliance RTF which would not

environment, it nurtures budding researchers through many

only provide me the financial resource but above all the

inspiring clinicians like my principle supervisor Dr. Usha Kini.

protected time to learn and apply the various molecular

Having worked with her team on the diagnostics aspects of

techniques while still retaining my feet in clinical medicine.

Hirschsprung disease over the past 2 years, we are now

While working with Dr Vrisha‟s for cartilage and bone regeneration involving human and animal experiments, we started to extend our thinking to one more field. Outcome of

Dr Sanjay K Chilbule

the osteosarcoma (OS), which is a commonest bone tumour

Christian Medical College, Vellore

in children, is not very favorable, due to heterogeneity and variable response to chemotherapy. With availability of patients and advanced laboratory in same unit, we started exploring this field, initially with collaboration with radiotherapy and medical oncology units at CMC Vellore. In literature, we found out that most of the CSC research work

After fellowship in paediatric orthopaedics at CMC,

done for OS is being done on cell lines. We started working

Vellore under supervision of Dr Vrisha Madhuri, I joined one

on cancer stem cells (CSCs) from osteosarcoma tissue from

of her research project to design the compliance monitored

patients with definite aim of translating this knowledge for

clubfoot brace (Padma Pada) in collaboration with

management of the osteosarcoma in future.

engineers from IISc Bangalore. It was quite inspiring to see

In addition of learning all the bench work related to

the replacement of age old brace by newer, better and

planned work, the Research Training Fellowship is providing

comfortable brace which parents are not ready to let of

the unique opportunity to a clinician like me to be part of

due to its definite advantage for child. This was possible due

basic science arena and to be able to develop a scientific

to Dr Vrisha‟s scientific disposition and the fact that clinician

temperament. This RTF is definitely metamorphosing the

themselves with the help of collaborators can bring in the

thinking process to apply the basic science for the

changes in the patient management adapting the research

orthopaedic disorders and to opt research as a career

in their prospectus.

continuing the clinical work.

4.

INDIA ALLIANCE

PUBLIC ENGAGEMENT CORNER DNA@70 Public Lecture Series

India Alliance organises several public lectures at various institutions across India, to give those interested in science an opportunity to interact with eminent scientists from around the world.

In 1944, Oswald Avery together with Colin MacLeod and

series, inventor of the field of DNA Nanotechnology, Dr

Maclyn McCarty made the landmark discovery that

Nadrian Seeman gave lectures in New Delhi, Hyderabad,

deoxyribonucleic acid (DNA), and not proteins, carry genetic

Kolkata and Shantiniketan where his talks on structural DNA

information and is therefore the basis of inheritance. In the 70

nanotechnology received very many questions from both

years since Avery‟s discovery, DNA has come a long way.

eager scientists and curious nonscientists. The third lecture in

India Alliance celebrated the discovery of DNA as a

this series, given by Dr Karen Nelson, focused on the human

hereditary molecule through a series of public lectures in

microbiome, emerging infectious diseases and implications of

various cities in 2014-15 given by researchers who have done

both for human health, which was very aptly titled “The Zoo in

pioneering work centered around the DNA molecule. The four

You”. The last lecture in the DNA@70 Public Lecture Series was

lectures in this series were given by Prof W Ian Lipkin (Center

given by Prof Shankar Balasubramanian of University of

for Infection and Immunity, Mailman School of Public Health,

Cambridge, co-inventor of next generation genome

Columbia University, USA) and Prof Nadrian Seeman

sequencing technology and co-founder of the company,

(Margaret and Herman Sokol Professor of Chemistry, New York

Solexa. His lecture “Decoding Human Genome on a

University, USA), Dr Karen Nelson (President, J Craig Venter

population scale” discussed the history of DNA sequencing,

Institute, Rockville, USA) and Prof Shankar Balasubramanian

the method that was developed by him and his colleagues at

(University of Cambridge, UK).

Cambridge University for rapidly decoding genomes and the impact of these technologies on life sciences, medicine and

Our first speaker in this series, Prof W. Ian Lipkin, a well-known

society. For those of you who missed his lectures in Delhi and

expert on the use of molecular methods for pathogen

Bangalore, here‟s a short report.

discovery, gave a lecture titled, “Bad bugs on the big screen: science fiction and fact in Hollywood” in New Delhi, discussed

Report: Prof Balasubramanian‟s lecture began with a humble

how filmmakers often mix fact with fiction when dealing with

yet engaging account of his scientific beginnings in the

science stories whereas his second talk “Small Game Hunting,

Department of Chemistry at University of Cambridge,

disease control in the genome era” in Bangalore, provided a

followed by his successful association with another chemist Dr

comprehensive review of pathogen discovery, microbiome

David Klenerman, along with whom he developed the

research and zoonotic diseases. Our second speaker in this

genome sequencing technology. He described how

5.

DNA@70 Public Lecture Series

contributions of various scientists in elucidating the DNA

to treat patients.

code- one of them being the father of genomics, Fred Sanger- influenced and shaped his work in this field. He

He acknowledged among others, the support of the

recounted how they accidently invented this

UK funding body BBSRC for giving wings to their idea

technology, as what they had really set out to study was

when it was in its most naïve and nascent stage almost

the motion of the DNA polymerase as it synthesised a

20 years ago.

single DNA molecule, using fluorescent tagging. He took the audience through the chemical processes of

Both the lectures were followed by an engaging

DNA polymerisation and how his lab exploited these

Q&A session with an audience of more than 250 in

processes to attach a fluorescent molecule on the

attendance at both venues, which covered scientific,

nucleic acid bases, which enabled them to visualize the

ethical, sociological and commercial aspects of the

different bases in a DNA molecule. This chemistry was

genome sequencing technology. Some of the questions

then employed to develop the sequencing technology,

raised at the session intended to discuss, the impact of

which is now being commercialized by Illumina after it

genome sequencing on society, genome of a

acquired the company, Solexa, originally formed by Drs

„perfectly‟ healthy individual, future of epigenome and

Balasubramanian and Klenerman in 1998. During his talk

protein sequencing and possibility of reducing the cost

at IISc, Bangalore, Prof Balasubramanian admitted, that

of the existing sequencing technologies, for which Prof

the practical question of how the information derived

Balasubramanian offered optimistic but practical

from the Human Genome Project can be made useful

answers. Apart from senior scientists, the audience

in comparing genomes from different individuals,

mainly comprised of young students and researchers,

inspired him to invent this quick method of DNA

who continued to interact enthusiastically with the

sequencing. Towards the end of the lecture, Prof

speaker well after the talk was over.

Balasubramanian described a few incidents where his method of sequencing had been useful for physicians to

Image Competition for India Alliance Fellows

perform diagnosis and develop personalised therapies

Public Engagement Competition for India Alliance Fellows

We are pleased to announce the launch of the Research Image Competition for our Fellows where we invite you to submit images related to biomedical research and healthcare. *Images could include:

To enable our Fellows to effectively and creatively engage with the

photographs, clinical & scientific images, hand-drawn illustrations

society about biomedical science, we announced the first rolling „Public

Images must convey a scientific principle or a relevant human health

Engagement competition‟ in May 2014. This competition is a valuable

perspective. *Images can be produced by individuals or by a team.

opportunity for our Fellows to showcase and share their Science with the

However, the Fellow has to play a key role in the production of the

Public and collaborate with other members of the society. The

image. *Images can be submitted for both science and human health

engagement can be through research, social activities, teaching, arts,

categories but only two for each category will be allowed.

movies/documentary and other modes of knowledge sharing with the

Submitting the images: Email your high-quality image with an easy-to-

central goal of educating and improving public awareness of science

understand description and a short image title to

and human health issues. To apply, please download the application

public.engagement@wellcomedbt.org. Please mention the names of all

form here and send the completed application form to

the people who were involved in producing the image.

public.engagement@wellcomedbt.org

​Deadline to submit images : ​15 October 2015

6.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

Novel insights into Colorectal Cancer Progression SPINK1 promotes Colorectal Cancer progression by down regulating Metallothioneins expression DR BUSHRA ATEEQ, Intermediate Fellow, IIT Kanpur Colorectal cancer (CRC) is the third most commonly

decrease in cell proliferation, invasion, soft agar colony

diagnosed cancer type; approximately one million individuals

formation and reduced tumor growth and distant metastases

worldwide are diagnosed with the disease each year. Anti-

in in-vivo model systems. Importantly, SPINK1 silencing led to

epidermal growth factor receptor (EGFR) therapies such as

up-regulation of various metallothionein isoforms, considered

monoclonal antibody (cetuximab) against EGFR are either

as tumor suppressors in CRC, which confers sensitivity to

administered as part of first-line treatment or as a final option

chemotherapeutic drug doxorubicin. Taken together, our

when other treatments fail. However, half of the CRC patients

findings strengthen the rationale for using the combinatorial

who harbor mutations in KRAS, NRAS, and BRAF genes acquire

treatment approach for the SPINK1-positive CRC patients. Our

resistance to anti-EGFR drugs, thus highlighting the necessity

study also demonstrates an important role for the SPINK1 over-

for additional targeted therapies. In the current study, we

expression in CRC disease progression, a phenomenon that

have shown that SPINK1 (Serine Protease Inhibitor Kazal type 1)

needs careful evaluation towards effective therapeutic target

is highly expressed among CRC patients and demonstrated

development.

the functional significance of SPINK1 in disease progression SPINK1 promotes colorectal cancer progression by downregulating Metallothioneins expression. R Tiwari, S K Pandey, S Goel, V Bhatia, S Shukla, X Jing, S M Dhanasekaran and B Ateeq. Oncogenesis (2015)

and metastases. SPINK1 over-expression in CRC has been associated with advanced stage of the disease, poor clinical outcome and metastasis to liver.

We have shown that silencing SPINK1 in BRAF mutation

Image: SPINK1-silenced or shSPINK1 colorectal cancer cells in the presence of anti-cancer chemotherapy drug doxirubicin.

positive WiDr colon adenocarcinoma cells demonstrate

Signal regulation at the mRNA 3’-end: Role of Phosphorylation Phosphorylation regulates gene specificity DR RAKESH SINGH LAISHRAM, Intermediate Fellow, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram Gene expression in humans involves multiple steps: from

the mRNA. Star-PAP is a non-canonical PAP that selects mRNA

messenger RNA (m RNA) synthesis in the nucleus to translation

target for polyadenylation. Star-PAP together with co-

in the cytoplasm. 3‟-end RNA processing is an essential step in

regulator PIPKIα controls expression of genes involved in

mRNA synthesis that involves addition of a polyadenosine (A)

oxidative stress response and apoptosis. We showed that

tail at the 3‟-UTR by enzyme called poly(A) polymerase (PAP).

phosphorylation of Star-PAP determines specificity of its target

Poly(A) tail is essential for stability and efficient translation of

gene expressions downstream of signaling pathways.

7.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

This study reports an in vivo phosphorylation site on Star-PAP at the N-terminus (serine 6, S-6) that determines Star-PAP specificity for oxidative stress response genes. The serine kinase CKIα phosphorylates the Star-PAP at S6 in the nucleus that retains Star-PAP within the nucleus. S6 phosphorylation is required for the Star-PAP-PIPKIα interaction and mRNA binding, both critical for target mRNA selection. However, this phosphorylation is indifferent to the expression of other target genes (apoptotic genes) regulated by DNA damage via other phosphorylation site(s) on Star-PAP. This is a novel mechanism where specificity of a poly(A) polymerase (or even a polymerase) for its target gene expression is determined by phosphorylation status. This study also shows a signal-mediated stimulation of CKIα kinase activity that regulates distinct mRNA. Star-PAP phosphorylation regulates PIPKIα interaction and determines target mRNA specificity. Mohan, N, Sudheesh AP, Francis, N, Anderson R, and Laishram, R.S. 2015. Nucleic Acid Res. (doi: 10.1.1093/nar/gkv676)

A global regulatory switch that controls cellular development in bacteria Sunish Kumar Radhakrishnan, Intermediate Fellow, IISER Thiruvananthapuram The circular nature of bacterial chromosomes leads to the

during early stages of the cell cycle in the dimorphic

formation of catenated (intermolecular linkage between two

bacterium, Caulobacter crescentus. A combination of DNA

replicated molecules of DNA) daughter chromosomes at the

replication S-phase specific synthesis and proteolysis ensures

end of each replication cycle. These catenated

that the presence of NstA is confined to the early stages of the

chromosomes need to be resolved by decatenation to

cell cycle. Mechanistically, we show that NstA exerts its

enable the proper segregation of the chromosomes into the

function by directly binding to topo IV, and that the activity of

dividing daughter cells. The decatenation function is primarily

NstA is controlled by the oxidation state during the cell cycle.

carried out, at the end of each replication cycle, by one of

Investigating further we discovered, for the first time, a cyclical

the DNA cutters, type II topoisomerases in bacteria,

fluctuation in the intracellular oxidation-reduction (redox)

topoisomerase IV (topo IV), which is also a quinolone

state of bacterial cells. Based on these evidences, we have

antibiotic target. Interestingly, the activity of topo IV has been

proposed the dynamic intracellular redox state as a novel

shown to be restricted to the late stages of the cell cycle

global regulatory switch that controls cellular development,

despite it being associated with the chromosome even during

which might have major implications on the cell cycle control

the early stages. The question as to how the decatenation

of bacterial pathogens exposed to the chemical warfare of

activity of the topo IV is regulated during the early stages of

the host immune system.

the cell cycle has remained unanswered.

A cell cycle-controlled redox switch regulates the topoisomerase IV activity. Narayanan, S., Janakiraman, B., Kumar, L., and Radhakrishnan, S.K. (2015). Genes & Development

Through a genetic screen we have identified Negative switch for topo IV decatenation Activity (NstA), as a novel negative regulator of the decatenation activity of topo IV

8.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

A new and free computational tool for HPV detection DR AMIT DUTT, Intermediate Fellow, ACTREC, Tata Memorial Centre, Mumbai

Human papilloma virus (HPV) accounts for the most common cause of all virus-associated human cancers.

genome and provide comprehensive HPV specific annotations (Fig 1).

However, despite large-scale genome wide DNA sequencing

Based on our evaluation with 116 exome, 23 transcriptome

efforts of the cancer genome there is no dedicated

and 1 whole genome, HPVDetector was able to identify

informatics tool to rapidly detect the presence of HPV in these

presence of HPV in 20 exome and 4 transcriptome data..

genomes, in an exclusive manner. In this study, we present a

Using the annotation module, we could show that viral gene

novel freely distributable computational tool “HPVDetector”

E7 was most widely represented among all the reads

(through a weblink download-- http://www.actrec.gov.in/pi-

detected that is a known viral oncogene. Additionally, the

webpages/AmitDutt/HPVdetector/HPVDetector.html.) to

integration module allowed us to validate known HPV

detect all known HPV types along with their sites of integration

integration sites, identify known fragile sites of the human

in the host genome using next generation sequencing data

genome as HPV integration site and novel integration sites (Fig

set, along with a widely compatible annotated reference of

2). In summary, HPVDetector is a simple yet precise and robust

143 HPV genome as a resource. This user friendly tool has

tool for detecting HPV from tumour samples using variety of

been designed for researchers who has limited computational

NGS platforms including whole genome, whole exome and

expertise using graphical user interface (GUI) that requires

transcriptome-- first tool of its kind solely dedicated to detect

minimal third party tools. Using HPVDetector, one can analyze

the presence of HPV types from a diverse variety of NGS data

paired end whole exome, whole genome or whole

set.

transcriptome dataset to detect all known HPV types along with their sites of integration in the host genome. The tool can run in two modes: a quick detect mode can identify coinfection of HPVs and their quantitative abundance while

NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome.P Chandrani, V Kulkarni, P Iyer, P Upadhyay, R Chaubal, P Das, R Mulherkar, R Singh and A Dutt.

integration mode can identify HPV integration loci in human

Schematic representation of all HPV16 and 18 integration sites in the human genome detected across cervical cancer samples using HPVDetector. Site of integration as determined by HPVDetector in cervical cancer samples is shown. HPV16 integration sites are depicted by circles and HPV18 by rectangles. Black, open and grey circles or rectangles represent integrations at known fragile sites, at known integration sites and at novel sites, respectively.

Conceptual The flowchart represents workflow for HPVDetector. Paired-end reads obtained from next-generation sequencing data are aligned to a combined Human–HPV reference database. All discordant read pairs with one read aligning to human and other to the HPV genome are identified and annotated utilising human and HPV database using an inbuilt annotator module.

9.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

Proteins regulating the formation of melaninproducing melanosomes DR SUBBA RAO GANGI SETTY, Senior Fellow, IISc Bangalore

Melanosomes are a class of lysosome-related organelles

endosomes. Our studies also found that another SNARE

(LROs) produced by specialised cells called melanocytes

protein, VAMP7, localised to melanosomes, controls the

which play a key role in skin color and photoprotection

trafficking of STX13 and its dependent transport steps. Taken

against ionizing radiations. Formation of this organelle requires

together, these studies show that BLOC-2 directs the recycling

efficient and accurate transport of melanin synthesizing

of tubular endosomes to maturing melanosomes and STX13-

enzymes from tubular or vesicular recycling membrane-bound

VAMP7 together mediate the membrane fusion between

sacs called endosome to pre-mature melanosomes, which

these cell organelles.

then undergo further maturation into fully pigmented melanosomes. This process is defective in Hermansky-Pudlak syndrome patients, due to the mutations in Biogenesis of LROs Complexes (BLOC-1, -2 and -3). However, the function of these complexes in LRO biogenesis is only partially known. In the Journal of Cell Biology publication, we have elucidated the function of the three-subunit protein complex, BLOC-2, in relation to LRO biogenesis, for the first time. Our studies demonstrate that BLOC-2 defines the specificity to the melanosomal cargo containing recycling tubular endosomes in targeting them to maturing melanosomes. Furthermore, mutations in BLOC-2 mistarget the recycling endosomes to multiple cell organelles such as plasma membrane, endosomes, lysosomes, Golgi and a subset to hypopigmented Dr Setty’s research image on the cover of Journal of Cell Science

melanosomes. Moreover, the SNARE proteins responsible for mediating these membrane fusion events are unknown. In the

I. STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis. Jani RA, Purushothaman LK, Rani S, Bergam P and Setty SR. J. Cell Sci. July 2015

Journal of Cell Science report, we have provided the first clear evidence that a recycling endosomal Soluble NSF (Nethylmaleimide-sensitive factor) Attachment Protein REceptor (SNARE) protein regulates the cargo delivery and biogenesis

II. BLOC-2 targets recycling endosomal tubules to melanosomes for cargo delivery. Dennis MK, Mantegazza, AR, Snir OL, Tenza D, Acosta-Ruiz A, Delevoye C, Zoger R, Sitaram A, de Jesus-Rojas W, Ravichandran K, Rux J, Sviderskaya EV, Bennett DC, Raposo G, Marks MS and Setty SR. J. Cell Biol.

May 2015.

of pigment granules. In addition, our studies show that mutations in a particular region of a SNARE protein, STX13, increased its activity, and redistributed it to melanosomes, indicating a role for that region in recycling the SNARE to

Please email your research stories and publications to public.engagement@wellcomedbt.org 10.

INDIA ALLIANCE FELLOW IN SPOTLIGHT

DR URVAKHSH MEHTA Early Career Fellow, NIMHANS, Bangalore Dr Urvakhsh Mehta is a clinician researcher and Wellcome Trust/DBT Early Career Fellow at the National Institute of Mental Health and Neurosciences (NIMHANS) Bangalore. Urvakhsh works in the area of cognitive neuroscience and was recently recruited as an Assistant Professor at the same institute. In this interview, he tells us the impact of his current research, how he came about to wearing a hat of a researcher along with that of an MD and what helps him to stay motivated..

What are you working on? And what impact do you hope it will have?

My research is focused on understanding schizophrenia from a “social brain disorder” perspective. This stems from important observations we have had in India, that are shared by colleagues from around the world, that individuals with schizophrenia have difficulties in perceiving, processing and responding to social cues in day to day interactions. An important neural-marker of these „social cognition‟ deficits in schizophrenia is a dysfunctional “mirror neuron system”. Mirror neurons have a dual role of firing while one performs an action, as well as, while one observes the same action. This unique property may provide the brain with a template to understand intentions underlying observed actions and hence may be relevant in processing social information. In my IA-funded research, I am using a combination of functional imaging and transcranial magnetic stimulation (TMS) to understand plasticity of the mirror neuron system and its role in supporting these complex social cognition abilities in individuals with untreated schizophrenia.

Results from this experiment will give us crucial information Urvakhsh with his current mentor Dr Jagadisha (Top) and with his ‘great-grand mentor Dr MS Keshavan(below)

regarding the connectivity of the mirror neuron system and its relationship to social cognition in schizophrenia. If transcranial magnetic stimulation can adaptively modulate the mirror neuron system, this „plasticity‟ can be further harnessed in

from my upbringing and the freedom my parents gave me

treating social cognition deficits using novel brain stimulation

to pursue my interests, my long-standing curiosity with

techniques in future.

cognitive neuroscience, my training in psychiatry, to the excellent support and mentorship I have received from my

What inspired you to become a clinician scientist?

teachers and guides at NIMHANS. The latter has actually enabled me to pursue a single line of research over the last

It has been a combination of factors that have inspired me

8 years now. Having trained in psychiatry and interacting

to choose the path of being a clinician scientist. These range

closely with individuals challenged with severe psychiatric

11.

INDIA ALLIANCE FELLOW IN SPOTLIGHT

URVAKHSH MEHTA

disorders like schizophrenia and bipolar disorder provides us

four years will surely go a long way in shaping me as an

with a unique vantage point to identify lacunae in our

independent clinician scientist in India. Lastly, I have been

understanding of these complex brain disorders from a

recruited as a regular faculty at NIMHANS (Assistant Professor of

translational perspective. I was introduced to the concept of

Psychiatry) this year. I am sure the recognition and the

social cognition by a visiting professor – I continue to have a

opportunities provided by the IA-Fellowship have had a positive

very fruitful collaboration with him till date and he fondly

impact on my selection process.

acknowledges me as his great-grand mentee!! I soon learnt that this special cognitive ability had evolutionary salience in

What keeps you going everyday?

humans – more so because of the well-documented coevolutionary association between brain size and social

This is something that is perhaps never a constant. Over the

complexity in several mammals. Early in my training days, this

years, I have learnt to draw inspiration and hope from wherever

“social brain” framework to study schizophrenia excited me,

I can – a sporting event, a catchy song, a new place I visit, my

as it provided an overarching conceptualization of

work, and most importantly, from people around me. My family,

different symptom dimensions of this disorder, ranging from

friends, teachers, students, colleagues, and patients are always

bizarre delusions and ego-boundary disturbances to avolition

there to give me so many “aha” moments that teach me

and disorganized behavior. I have since then studied the

something new or generate ideas.

clinical importance and neurobiology of these intriguing

Also, music is something that keeps me going. It is my default

cognitive abilities in patients with schizophrenia.

mode – if I am not doing anything, music is my constant “brain worm”. Anything from Shahid Parvez and Rashid Khan to Mark

How has Wellcome Trust/DBT India Alliance funding helped you and your research?

Knopfler and Eagles can help me rewind.

The India Alliance Fellowship could not have come at a better time for me in my career. It has certainly had a huge impact. First, it was due to the IA-Fellowship that I could join NIMHANS as a faculty in the department of psychiatry and continue my line of research and clinical work in parallel.

Second, the financial grant through this Fellowship has helped me start quite a complex experiment that is both technology and manpower intensive. The selection committee has been sensitive to my needs and has made some really important suggestions that I have been happy to implement. Third, this Fellowship has given me an opportunity to train in novel research applications of brain imaging and

This image shows how target regions from functional MRI activation maps, superimposed on to the subject's structural brain image can be precisely stimulated using infra-red camera guided TMS coil placement.

neuronavigational TMS at Boston. Both India Alliance and NIMHANS have been supportive and permitted me to pursue

Find out more about Urvakhsh‟s research here

a PhD in psychiatry. My training and experience over these

12.

FEATURE ARTICLE

PEEKING INTO THE HIV INFECTED CELLS DR AMIT SINGH, Senior Fellow

Since its discovery, Acquired Immune Deficiency Syndrome or AIDS has caused an estimated more than 36

of basic tools to directly monitor the internal environment of cells harboring virus in latent or reactivation state.

million deaths worldwide. Its causative agent, the Human Immunodeficiency Virus (HIV), has thus been an active topic

In this context, our research group is interested in

of basic and translational research. India has the third largest

developing basic technologies to understand the physiology

HIV epidemic in the world accounting for ~ 2.1 million infected

of HIV infected cells during various stages of infection. The

people. Socio-economic conditions such as malnutrition,

information generated from these methodologies can then be

smoking, alcohol, drugs, and poor hygiene are some of the

exploited to develop high-throughput cellular screens (HTS) to

factors increasing the risk of HIV infection. Despite the

eradicate latent reservoirs of HIV. Studies at both the cellular

availability of multiple anti-retroviral therapies against HIV, the

and organismal levels revealed that HIV induces major

disease remains a chronic, life-long infection due to the ability

metabolic changes in the human host cells. Some of these

of virus to stay hidden within infected blood cells. These

changes include depletion of amino acids, increased sugar

cellular “reservoirs” maintain HIV in a latent state where body‟s

metabolism, energy depletion, and depolarised membrane

immune response is unable to sense their presence, and

potential. We found that in addition to metabolic changes,

current anti-HIV drugs show limited activity.

levels of reactive oxygen species and antioxidant, glutathione (GSH), are markedly influenced during HIV latency and

The cellular reservoirs of latent HIV are found in diverse

reactivation. Healthy human cells produce oxygen free

anatomical locations including the genital tract, bone

radicals called reactive oxygen species (ROS) as a byproduct

marrow, brain, lymphoid and the lymphoid tissue. These

of normal metabolism. However, various conditions including

reservoirs persist, even in the presence of Highly Active

chronic infection, metabolic dysfunctions, ageing, and

Antiretroviral Therapy (HAART), today‟s standard of care.

prolonged chemotherapy can result in accumulation of these

Understanding the fundamental basis of HIV-1 latency to

ROS and generation of toxic levels of oxidative stress.

develop effective intervention strategies remains one of the

Interestingly, we discovered that heightened oxidative stress is

core research issues in the field. Within this theme, one

one of the primary causes of reactivation of HIV from the

proposed eradication strategy is to activate these latently

latently infected cells. Since, GSH serves as a major cellular

infected cells followed by killing using HAART. The

antioxidant and functions as a protective shield against the

rationalisation for this kind of strategy can be two-fold. First, by

oxidative stress, any changes in the cellular ROS levels directly

stimulating latently infected cells to reactivate the virus can

perturbs GSH balance. Our team has devised a non-invasive

potentially lead to more rapid death of the infected cells due

biosensor methodology, new to the HIV field, for precise

to HIV replication. Second, once reactivated, the cellular

imaging and measurements of GSH levels within the sub-

reservoir producing HIV will be recognised by the immune

compartments (e.g. mitochondria, endoplasmic reticulum,

system. Lastly, simultaneous use of a reactivating agent along

and cytosol) of HIV infected cells. Earlier methods use whole

with HAART can prevent subsequent spread of infection.

cell or tissue extracts, which destroy real-time information

However, many of the research efforts in this direction yielded

related to the variations in GSH levels at a sub-cellular

no results due to generalised cytotoxicity associated with the

resolution.

reactivating agents. We believe that this is mainly due to lack

13.

FEATURE ARTICLE

PEEKING INTO THE HIV INFECTED CELLS

alarming rate. Because of this, World Health organisation (WHO) has recently recommended collaboration between HIV and TB control strategies. Therefore, we believe that studying the basic biology of Mtb and HIV in coinfection models is poised to make more beneficial impact than studying these pathogens alone. In light of this, we exploited our biosensor technology and discovered that certain bioactive molecules (e.g. complex lipids) produced by Mtb specifically interacts with HIV infected cells and Eradicating HIV reservoirs by “Shock and Kill” strategy: Cells latently infected with HIV can be treated with small molecule redox modulators to decrease their antioxidant capacity. This would result in inactivation and elevated replication of HIV leading to HIV-induced cell death and recognition of HIV infected cells by the immune system. Simultaneous use of HAART can prevent spread and transmission of new HIV particles to the neighbouring bystander cells.

disturb GSH balance to facilitate HIV reactivation. Since TB is the major cause of HIV related deaths,

our findings have major mechanistic and therapeutic Using our novel biosensor technology, we discovered that

potential for both TB and AIDS.

latently infected cells have higher levels of GSH which may facilitate the long term persistence of HIV. In contrast, active replication of HIV rapidly depletes GSH levels. We also

Dr Amit Singh is an assistant professor at Indian Institute of Science, Bangalore and WT/DBT India Alliance Intermediate Fellow (2009). Hi research work focuses on understanding fundamental mechanisms regulating mycobacterial persistence and redox basis of HIV infection. As also mentioned in this piece, his research group has “developed a novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infection”.

disclosed that a modest decrease in intracellular GSH levels and associated increase in ROS levels are sufficient to reactivate virus from latency without causing cytotoxicity.

Our findings, for the first time, provide precise numerical indicators of how much cellular physiology can be perturbed to reactivate virus from the sleeping mode without eliciting toxic side effects. This may help researchers to adopt a "shock-and-kill" approach in which virus could be reactivated by redox modulating compounds and subsequently flushed by current anti-HIV drugs. The fluctuation of GSH levels detected by our biosensor also helps to delineate cellular pathways which control latent and active stages of infection.

In addition to infection with HIV, co-infection with another human pathogen, Mycobacterium tuberculosis (Mtb), the

To find out more about his research, visit his lab website.

causative agent of tuberculosis (TB) is adversely impacting the HIV and TB control programmes worldwide. Number of people dying with HIV-TB coinfection is increasing at an

14.

IN CONVERSATION WITH..

Dr Ajit Varki

Dr Ajit Varki is a distinguished professor of medicine and cellular and molecular medicine, and co-director of the Glycobiology Research and Training Center at University of California, San Diego, USA. He is also a co-director for the UCSD Center for Academic Research and Training in Anthropogeny. Dr Varki was one of the speakers of the India Alliance Public Lecture Series “Evolution of Human mind” in 2014 and gave fascinating talk titled “Adventures in Anthropogeny : What makes us Human” in different cities across the country. In this interview he very candidly takes us through his scientific journey, the multidisciplinary research he is involved in and shares some great advice for aspiring researchers.

What motivated you to become a scientist?

science of understanding glycans. This of course is the nature of science; you never know where it leads you.

For as long as I can recall in my childhood, I wanted to become a physician – to be involved in the care and healing of the sick. However, I was very fortunate to gain admission into a very special medical school, Christian Medical College, Vellore. In those days (as it is today) the medical education at CMC includes exposure to scientific inquiry and research.

During my time there, I had the good fortune to interact with many prominent physician/scientists as well as basic scientists.

Still, I first and foremost wanted to be a physician. But I gradually came to realize that while medicine has many aspects that are still an art form- a major aspect has to do with understanding the human body, biology and science.

Realizing at the time that there were very few opportunities in India for a physician to continue doing serious science, I decided to migrate to the United States where this type of combination was very common. I was very fortunate to eventually gain access to training at one of the best centers at Washington University at St. Louis. Thus, I was able to combine my continued interest in medicine with its scientific aspects, particularly in hematology and cancer biology. Initially I wanted to pursue the then exciting new approach of bone marrow transplantation, but I decided that before I got into this I should learn more about the surfaces of human blood cells. Reading more about this I came to realize that all other cells in cell sin the body are covered with a dense complicated coating of sugar chains that very few people were studying. Eventually my postdoctoral training, working

Could you briefly take us through your scientific journey and about your interest in the human evolution. How does that tie in with your research in the field of Glycobiology.

I decided to start my independent career combining medicine with the study of the special class of sugars, called sialic acids. Early in my stint as an assistant professor, I happened to see a patient being given a form horse serum for the treatment of a disease called aplastic anemia. Not surprisingly, she developed an allergic reaction to the horse serum after a few treatments. In reading the literature, I was very surprised to find that others had just reported the allergic reaction was not against horse proteins, but against horse sialic acids. At first this did not make any sense to me as sialic acids are present in all mammals, in horses as well as in humans.

Eventually I realized there was one particular kind of sialic acid present on horse serum glycoprotein that was completely missing in humans. It took me another ten years, but I finally discovered the first known genetic difference between humans and chimpanzees (our closest living evolutionary cousins), in a gene involved in modifying Sialic acid. This in turn led me to the field of anthropogeny or explaining the origin of humans. Thus as you can see, science led me from medicine to glycobiology then into anthropogeny, and I now combine all 3 disciplines in my scientific activities.

with Stuart Kornfeld ended up with the discovery of a genetic disease in a rare human disorder that had very little to do with

If you were not a scientist, you would be..

blood or cancer. But I became completely immersed in the

Lead singer in a rock 'n roll band

15.

IN CONVERSATION WITH..

Dr Ajit Varki

Dr Varki after his lecture at Indian Association for the Cultivation of Science, Kolkata with IA Grants Adviser, Dr Ranjana Sarma, IA Fellow, Dr Benu Brata Das (L-R) Dr Varki at Bangalore Science Forum

back to square one. In relation to doing experiments the other

What according to you are the challenges in your field of research?

important piece of advice I got was from a famous scientist named Ray Lemieux, a chemist in Canada. Ray pointed out to me that the great majority of experiments that we do are

Both fields in which I work face similar challenges. In the first

ones in which we already sort of know what kind of result to

case (anthropogeny) there is certainly a lot of interest in the

expect. As Ray put it, “if you do an experiment and you get an

field, but the amount of available information is very limited. In

expected result, you have not done an experiment”! In other

the second case (Glycobiology) you have an even bigger

words experiments are often too predictable and those are

problem in that most scientists are only dimly aware of this

the kind we tend to do more often. Another interesting

“dark matter of the biological universe”, which affects every

corollary is the most interesting outcome of an experiment is a

cell and every biological process in the body. In the end the

completely unexpected result. As the famous science writer

biggest challenge faced by anthropogeny is not only the

Isaac Asimov put it: The most exciting phrase to hear in

difficulty in gaining new information, but also in the synthesis of

science, the one that heralds new discoveries, is not “Eureka”

information across many different fields of human knowledge.

but “That's funny...”. Too often these days I find that young

In the case of glycobiology the same two problems apply.

people will do experiments and not getting the expected

Added to that is the difficulty that most scientists poorly aware

result they become disappointed, abandon their line of

of even the basic information. But in both fields things are

reasoning and often do not even inform their advisors about

changing. More and more information is becoming available

what they found, thinking somehow that they have failed.

and I am fortunate and excited to be involved this phase of

Actually, the time to get most excited is when the experiment

development.

does not work out the way you thought, even though you designed it well and had all the right controls.

What is the best advice you have ever received?

There is a tendency to assume that much of science consists of

Your message for young students and researchers.

thinking up experiments, quickly getting results, and moving on. Two pieces of advice stick in my mind, from my mentors.

The pursuit of science (and the associated issues like winning

Stuart Kornfeld taught me that the most important thing about

grants and getting papers accepted) can be sometimes slow-

doing an experiment is the amount of time you spent thinking

going and frustrating, and one usually lives for that occasional

about what you want to do, why you want to do it, how you

day when the big breakthrough occurs. But in the long run it is

are going to go about it maximizing the chance of getting

hard to think of the most satisfying profession (other than that

well-controlled interpretable results. This used to be the norm in

of a successful rock 'n roll singer or orchestra conductor). Most

the early days when reagents and resources were precious.

of my classmates who went through medicine and did not

Nowadays there is an unfortunate tendency for young

pursue a scientific career are now bored with their professions,

scientists to do “quick and dirty” experiments to “get an idea”

and trying to retire. I wake up every morning and I cannot wait

of what might be happening, before doing the "real"

to get to work!

experiment. In fact such “quick and dirty” experiments waste a huge amount of time and resources and one is often

To find out more about Dr Varki‟s research, visit his lab website

16.

OPINION ARTICLE

Early Career Fellows: DR MEGHA & DR NEHA VYAS,

Early Career Fellows

For an academic research career in the life sciences,

professional path are struggling; their interactions with the

conventionally, a highly productive postdoctoral stint is

Indian scientific community as prospective faculty applicants

considered necessary. To meet this benchmark of productivity

reveal a dominant perception that EC Fellows should be

as well as to hone their research skills, the de facto route an

comparable to those who complete their postdoc overseas. Is

India-trained PhD student takes is to do a postdoc overseas.

this perception justified? This article attempts to provide the EC

Other factors such as better salaries, higher standard of living,

Fellow perspective, and with the questions raised, hopes to

and exposure to cutting-edge research also motivate this

start a conversation in the Indian scientific community about

migration. Additionally, the advice that overseas postdoctoral

the future of postdocs in India.

research credentials are preferred for a faculty job in India plays a significant role in this decision. Reality underscores this

The key yardstick used to assess scientific performance is

advice: a majority of junior faculty hired in top Indian research

publication record. Are the India Alliance and Indian faculty

institutions have returned from a postdoc overseas. Further

screening committees expecting EC Fellows to deliver a

testament to the popularity of this status quo is that both DST

record similar to a postdoc in the West? From the Fellows‟

and DBT have Fellowships exclusively for those returning from

point of view, this is an apples-to-oranges comparison. The EC

abroad.

Fellow is working on an independent research idea right from the start of their Fellowship, while a conventional postdoc

Shaking up this paradigm are researchers who choose to

typically works on ongoing projects in the Supervisor‟s

pursue a postdoctoral career in India. This option has gained

laboratory which may later morph into an independent

traction due to the increasing availability of institutions,

research project. This research independence of the EC

laboratories and funding opportunities. At the leading edge of

Fellow, though, comes at a cost. Experimental systems and

enabling this is the Early Career (EC) Fellowship scheme, which

logistics have to be standardised, and sometimes procured

has done much to attract a cohort of ambitious postdocs to

and set up. In some cases, the Fellowship Supervisor‟s research

research in India. These Fellowships are generously funded,

and the Fellow‟s project have little overlap, and this further

empowering Fellows to dream big, set up and visit

exacerbates the time lag experienced to get publishable

international collaborations, and tackle fundamental science

results. Another way to enhance research output is to build

questions for a length of time that allows for rigorous pursuit.

collaborations, within the laboratory and outside. The EC

The EC Fellowships thus provide a great opportunity for a

scheme allows for the latter, but the former is completely

fantastic early career start. But this prompts an obvious follow-

missing from the Indian laboratory landscape; more than one

up question: what is the professional future of the EC Fellows?

postdoc in an Indian lab is a rarity. Even with international

The mandate of the EC Fellowships is to support ideas that can

collaboration, the EC Fellows are working on their ideas and

act as a springboard to the Fellow‟s future independent

not on the collaborators‟ ideas, further reducing the chances

research program. This suggests the expectation that Fellows

of the work in the collaborators‟ laboratory being

would continue to pursue an academic research career.

independently published. These circumstances affect the

Given the lopsided supply and demand situation, not just in

output that EC Fellows can have by the end of their tenure,

India but world over, it should not be surprising that not all EC

and argues that EC Fellows may not have track records similar

Fellows would be successful in getting academic jobs. Even

to those doing a conventional postdoc in the West.

after taking this into account, Fellows wishing to pursue this

17.

Early Career Indian Science Fellowships Funding Community Productivity Collaborations India Scientific

policy Academic Impact Factor Post-doc International Independent Research Post-docing

Future

Vision

Transition Training Cutting-edge Output DBT Culture Publications Junior faculty Supervisor Opportunities Alliance Postdoctoral association

If the India Alliance and the Indian scientific community

would only be possible if the community recognises this

intend to encourage postdoc-ing in India, a more nuanced

cohort. To this end, the NCBS-inStem campus postdocs have

assessment of Fellows performance might be considered.

formed a postdoctoral association, which aims to assist postdocs in developing themselves professionally through

First, EC Fellows‟ publication record can be benchmarked

teaching and other career-related activities. A postdoc-

against the limitations inherent to doing research in India. To

specific symposium is being planned to make postdocs

do this, Indian institutions can reflect on the publication

visible as a research cohort within the Indian scientific

record of their own junior faculty in the first five years of

community. Although geographically restricted at present,

having set up their independent laboratory.

the formal recognition of the association at the policy level,

Second, the quasi-independence of the EC Fellow in

and its implementation in institutions, would be helpful.

terms of research idea, execution and future vision can be

To conclude, the following questions require reflection by

acknowledged.

the Indian scientific community, policy makers and the India

Third, new scientific directions created by the Fellows in

Alliance: is India ready to host a postdoctoral culture? Are the issues raised here, of publication record and postdoc

their Fellowship Supervisor‟s laboratory can be considered.

mentorship, important to the development of postdoctoral

Fourth, the ability to innovate and deliver on projects

culture in our country? As a community, should we

independently, in an Indian research environment should be

encourage postdoc-ing in India? If yes, are there sufficient

valued. The EC Fellowship experience provides the Fellows

opportunities and mechanisms to enable India-trained

with an opportunity to develop a realistic idea of what can

postdocs to successfully transition into a career of their

be achieved in India and how.

choice? A brain-storming session on the points raised here would be useful not just for the future of EC Fellows, but all

These parameters should not get masked in the shadow of the

postdocs in India.

sole currency of the current evaluation system i.e., “impact factor of publication(s)”.

In the West, a postdoctoral culture has existed for more than 30 years, and postdocs are considered a major, indispensible work force in research. This has resulted in a system for nurturing postdocs and helping them transition to future careers, Megha

academic or otherwise. A similar research environment is yet to

Neha Vyas

evolve in India simply because there was never a sizeable cohort of postdocs. But now, since both funding agencies and

Authors of this piece, Drs Megha (ECF 2013) and Neha Vyas

institutions are building postdoc cohorts, a framework to foster

(ECF 2010) are India Alliance‟s Early Career Fellows based at

postdocs needs to be developed. Managing a PhD is very

National Centre for Biological Sciences and inStem,

different from managing a postdoc, and timely strategic

Bangalore, respectively.

advice, especially if the postdoc is interested in an academic Disclaimer: The opinions expressed within this article are the personal opinions of the author(s). The information, facts or opinions appearing in the article do not reflect the views of the India Alliance.

career, will be valuable. Skill development opportunities and career planning resources for postdocs in Indian institutions

18.

REPORT

Leadership and management: two sides of the same coin?

DR SHITAL SARAH AHALEY, Early Career Fellow

“There is a difference between leadership and management. Leadership is of the spirit, compounded of personality and vision; its practice is an art. Management is of the mind, a matter of accurate calculation .... its practice is a science. Managers are necessary, leaders are essential.’’ Field Marshal Lord Slim In the academic world, we are trained to hold a pipette, design an experiment, write reports and papers, formulate and test a hypothesis and yet when we establish a lab, we are expected to manage the lab funds and graduate students, lead a group and achieve goals. I guess this is the only field where we are trained with a specific skill set and then need a different level of advanced skill set to run a lab. We have to be leaders and managers; we have to practise the art of leadership and the science of management!

In academia, many learn management skills as and when they progress in their career. The skills are acquired through experience. There are times when one is successful at a task and other times where one fails. One formula does not fit all situations or one type of training exercise does not apply to all graduate students. Many have mentors in their respective institutes to whom they turn to for advice during difficult circumstances.

Others discuss with colleagues who may or may not have faced similar situations. Yet there are some who are confident enough to handle situations without any help. In any case, one has to arrive at a decision, the consequences, good or bad, have to be faced by the group leader/PI. With trial and error, the PI finally sets up a lab, working ethics, managerial techniques, lab environment and eventually a leadership style. The PI is definitely managing a lab, but may or may not be a good leader. C. J. Fitzsimons, the Leadership Sculptor, who undertakes Laboratory Management course for EMBO defines leadership as „the art of maintaining a dynamic balance between influencing others, by word and deed, to reach common goals and ensuring their development and well-being.’

The EMBO management training for postdocs and group leaders addresses important skills including, staff selection, leadership and delegation, effective problem solving and communication. I attended the training for post-docs in May at Leimen, Germany with C. J. Fitzsimons and Sabine Gramm as our guides. If put in one sentence, the skills that were addressed are the ones we are already aware of to some extent, but the trainers put them as tangible formulas or theorems before us. For example, in “Making the Right Moves”, Edward O‟Neil provides us with an equation:

Briefly, the course covered the following topics such as, impact of cultural differences, leadership profile and skills, PI/group leader role, impact of working environment, working with values, communication, feedback and criticism, team dynamics, conflict management, motivation, delegation, interview preparation. We spent approximately 60 minutes on each of these topics. Some topics like PI/Group leader role required 120 minutes. Each of the topics was elaborated based on extensive research done in the field by experts. There were 17 participants of different nationalities- all of us were post-docs in different countries, yet it was heartening and somewhat reassuring to see that we faced similar problems and had similar questions. One thing I realised significantly during this workshop was the lack of post-doc culture in India.

The principles that were discussed in the course are not only confined to an academic set-up but can be applicable in an industry or for that matter any situation that requires teamwork.

While we all possess certain leadership qualities, this course helps us to identify and work on our qualities based on our personality type and circumstances. All PIs have to run a lab and they do so to the best of their capability. This course will definitely help you in discovering your leadership style and furthermore in setting up a high performing lab.

Prof. Katja Schmitz, a participant of the course, from Clemens Schöpf Institute puts it aptly, “If you’re only interested in acquiring a few tools, read a book or visit a seminar. If you’d like to find out more about yourself and how that impacts your leadership, get a coach.”

For further information visit www.leadershipsculptor.com and www.embo.org/events/laboratory-management-courses

Dr Shital Sarah Ahaley is an Early Career Fellow based at Indian Institute of Science Education and Research, Pune. Find out more about her here.

Leadership = Vision + Relationships + Tasks We all have an understanding of leadership and some ideas about how a good leader should be, but this simple equation gives us a concrete perception of the term. Additionally, each term of this equation, viz. vision, relationships and tasks, were further spelled out to improve our understanding.

19.

INDIA ALLIANCE STAFF CORNER

Dr Dipanwita Sengupta, is one of the senior members in the grants team who joined this organisation in June 2012 as a Grants Adviser.

Since then, Dipanwita has been juggling various grants-related responsibilities and outreach activities at the organisation. In this interview she takes us through her childhood days, her interest in music, finding inspiration in prominent Bengali figures and more..

DR SUVEERA DHUP, Grants Adviser Dr Suveera Dhup, is one of the senior members in the grants team who joined this organisation in September 2012 as a Grants Adviser. Suveera has been involved with many aspects of IA, from grants-related work to SciComm workshops and website and is currently the secretary of the Margadrashi scheme. In this interview she takes us through her family history, reminisces about her childhood days, her love for ghazals, people who inspire her and more..

How has your India Alliance journey been so far?

Apart from working with an excellent team at the Alliance, I get to be in touch with the best minds in research. Also, it gives me an opportunity to meet young PhD students and postdocs through Scicomm workshops. Their infectious energy and questions drives me to keep myself updated with latest trends

What is your background?

My family is quite multicultural with my mother who hails from North West Frontier Province and my father from Lahore. During partition, both my parent‟s families migrated to India and made Delhi their new home. Atmosphere at home was that of discipline, however it gave us freedom to explore the cultures and traditions of both the families. The best part of this was the variety of food that my sister and I were exposed to. I fondly remember, how as kids, we used to wait the whole year for our Dussehra holidays when we got the chance to visit our maternal grandparents. Every vegetable at their place was grown in the small kitchen garden that my grandfather maintained in the backyard – from tomatoes to bhindi (lady finger), from mangoes to pomegranates – all these were

in science. Another good thing about our organization is its capacity to evolve with time and situation without stagnation.

When not busy on the job, what do you enjoy doing?

With the birth of my twin daughters last year, my personal interests have taken a back seat. When not in office, I am busy attending to the whims and fancies of my little angels. My reading habit has changed gears, from history and thrillers to parenting books and articles. I have a good collection of old Hindi songs and ghazals, which I think (and I hope) my daughters like listening too.

Who inspires you (living or dead)?

Actually two people. First being my Nanaji, paternal

grown in-house. After a whole day of mischief, we used to get

grandfather. He was a self-made man. During partition, he

dressed up in sweaters to go watch Ramlila at the colony park

came to India barefoot with his family. Without any aid, he

– something which we don‟t see in the city anymore.

rose from extreme paucity to becoming a very successful

Being in Delhi was an added advantage when it came to my

businessman. I never saw him relaxing; he worked till the very

education; the city being host to the best of schools, colleges

end. He was a freedom fighter, philanthropist and a strong

and renowned universities in the country. Even though I belong

believer in girl education.

to a family of engineers, there was no pressure on us from our

The second is the renowned astronaut, late Kalpana Chawla.

parents to follow this family tradition. I completed my studies,

From an ordinary girl born in Haryana to the first Indian-born

right from the schooling to PhD, here in Delhi. My first Postdoc

woman in space! She fought for her dreams and realized them

was at CNIC, Madrid where I started a project on aging and

too. A quote from her last email - "The path from dreams to

oxidative stress. Economic crisis there took me to Pierre

success does exist. May you have the vision to find it, the

Sonveaux‟s newly established group in Brussels where I worked

courage to get on to it, and the perseverance to follow it"

on tumor metabolism for 3 years. In 2012, I decided to move

inspires many. Interestingly, I share my birthday with her.

back to India and joined the Alliance as a grants adviser.

20.

EXTERNAL EVENTS

India Alliance Travel Awards

9 travel awards were made to PhD students, Postdocs and Young Investigators to cover travel expenses for this meeting.

These were announced on 1 August 2015. The list below is the final list of Travel Awardees (excludes those who could not accept the award). The list is according to the Submission Number and not according to priority.

The following will receive travel support of up to â‚Ź 500 each.

1588 1528 Uzma Saqib, IIT Indore 1591 1533 Mirza Saqib Baig, IIT Indore 1598 1540 Swarnendra Singh, NII, New Delhi 1623 1572 Abhinita Borah, IIT Bombay 1632

Manika Kargeti, IIT Bombay Yasir Khan, Aligarh Muslim University Alok Pandey, CIMAP, Lucknow Arun Prakash Mishra, CCMB, Hyderabad Thangaselvam Muthusamy, NCBS, Bangalore

Clinical Research Training 2015

Date/time: 31 October - 09:00 to 2 Nov 2015 - 17:15 Event location: The George Institute for Global Health New Delhi, India

This training course has been developed to provide an overview of research study design and methods to young researchers who have just completed their clinical training or are in the early stages of a research career. The primary aim of the course is to provide knowledge, with emphasis on practical experience in basic epidemiology and biostatistics so that clinicians can feel confident in their approach to conducting a research project, and taking the output to the next step, i.e., publication.

For more information on this workshop and how to apply, visit the website

Click on the image to find out more about YIM2016

21.

IMAGES IN THIS ISSUE

Credit R. Dourmashkin, Wellcome Images HIV particlesHuman immunodeficieny virus (HIV-1) particles showing the core and the envelope.

Transmission electron micrograph Collection: Wellcome Images

Credit Dr Ajit Varki. From Cell Reports Nidoviruses attached to sialic acid (in blue, hemagglutinin esterase).

Cover image (original) by Dr Subba Rao Gangi Setty, Senior Fellow, IISc Bangalore Image description: Bright-field and immunofluorescence microscopy image of wild-type mouse melanocytes expressing mutated STX13 (a recycling endosomal Qa-SNARE), which results in its mislocalisation to melanosomes. Green, mutant STX13; red, a melanosome-resident protein TYR; black dots, melanosomes captured with bright-field microscopy.

Please send your feedback, suggestions and contributions to public.engagement@wellcomedbt.org Follow us on 22.