India Alliance Newsletter I Issue 4 I July 2015

News & Views Issue 4, July 2015

ISSUE 4

INDIA ALLIANCE

EDITORIAL Somewhere, something incredible is waiting to be known - Carl Sagan As we enter the second half of this year with the fourth issue of our newsletter (and a brand new website!) , we are very thankful to all those who have taken time out to generously contribute to this newsletter thus far.

In this issue, we give you a roundup of news on our Fellowship schemes, updates on the IA funded-research, public engagement and science communication activities along with some interesting articles and interviews.

On the Fellowships front, full applications for Clinical and Public Health fellowships, Research Training Fellowships, Margdarshi Fellowships and preliminary applications for Early Career Fellowships (basic research scheme)are currently under review. Deadline to submit preliminary applications for the Senior and Intermediate Fellowships (basic research scheme, May 2016 competition) is 13 August 2015.

We will be holding two-day Science Communication workshop in September 2015 in Hyderabad (applications under review) and the next one-day SciComm101 workshop will be held on 23 July 2015 at Jamia Millia Islamia, New Delhi. We conducted two SciComm101 workshops at the University of Kashmir in May 2015, first of its kind in the valley. Dr Shaida Andrabi, our host at the University, writes about the importance and impact of these workshops in this issue. In the Public Engagement corner, Intermediate Fellow, Dr Mukund Thattai and his colleagues write about their project ‗Bodystorming hits Bangalore‘- first Public Engagement project of a Fellow funded by the India Alliance. Prominent scientist and co-inventor of a DNA sequencing technology, Prof Shankar Balasubramanian gave the fourth and final lecture in our DNA@70 Public Lecture series at NII, New Delhi and IISc Bangalore. For those of you who missed Prof Balasubramanian‘s lectures, we feature his interview in this newsletter where he recounts his scientific journey, shares sound advice and much more.

Also, in this issue, our Intermediate Fellow and wildlife ecologist, Dr Farah Ishtiaq talks about her passion for science and birds in the Fellow in Spotlight section. Read about the recently published research of our Fellows Drs Mahak Sharma, Soumen Basak, C V Srikanth and Thomas Pucadyil in the Research Highlights section. In the article titled ―Fat cells and insulin resistance: unraveling the physiological underpinnings of the epidemic” Early Career Fellow, Dr Joe Varghese, describes the links between adipose tissue inflammation and insulin resistance in the background of his work.

Our Intermediate Fellow, Dr Arun Sripati‘s short piece “what is good science and when do you know you are doing it?” offers interesting perspectives and implicitly encourages scientists to seek answers for these questions. In the staff corner section, our Grants Adviser, Dr Dipanwita Sengupta, gives us a glimpse of her early life, interests and tells us what has made her India Alliance journey so special. Our heartfelt appreciation for all the aforementioned people for their valuable contributions for this issue. Last but never the least, for the cover image, we extend our gratitude to Dr Farah Ishtiaq for sharing a lovely picture of a Parus Major (Great Tit) from her field research outing.

We will continue to bring to you interesting scientific discoveries and discussions.

Happy Monsoon season, Sarah Iqbal Public Engagement Officer

1.

CONTENTS

3

CALL FOR INDIA ALLIANCE FELLOWSHIP APPLICATIONS Senior and Intermediate Fellowships (Basic research scheme)

4 INDIA ALLIANCE SCICOMM WORKSHOPS 5

7

INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER A dance-science interaction at the National Centre for Biological Sciences

by Dr Mukund Thattai and colleagues INDIA ALLIANCE RESEARCH HIGHLIGHTS Featuring recent research articles by Fellows, Drs Mahak Sharma, Soumen Basak, CV Srikanth, Thomas Pucadyil

10

INDIA ALLIANCE FELLOW IN SPOTLIGHT Dr Farah Ishtiaq, Intermediate Fellow

12 FEATURE ARTICLE Fat cells and insulin resistance: unraveling the physiological underpinnings of the epidemic, by Dr Joe Varghese, Early Career Fellow, CMC Vellore

14

IN CONVERSATION WITH..

Prof Shankar Balasubramanian, Herchel Smith Professor of Medicinal Chemistry at University of Cambridge, UK

15

16 17

VIEWPOINT What is good science and when do you know you’re doing it?

by Dr Arun Sripati, Intermediate Fellow, IISc Bangalore INDIA ALLIANCE STAFF CORNER Dr Dipanwita Sengupta, Grants Adviser, India Alliance EXTERNAL EVENTS

2.

INDIA ALLIANCE FELLOWSHIP ANNOUNCEMENT

CALL FOR APPLICATIONS SENIOR AND INTERMEDIATE FELLOWSHIPS IN BIOMEDICAL RESEARCH

Recommended Awardees for

Senior and Intermediate Fellowship (Basic) from May 2015 interview round

Deadline: 13 August 2015

Intermediate Fellowship

Preliminary applications are invited for the two Fellowship schemes in basic research category: Intermediate Fellowships and Senior Fellowships.

Dr Sabyasachi Rakshit, Indian

Institute Of Science Education And Research, Mohali

Dr Smarajit Polley, Bose Institute, Kolkata

Senior Fellowships: For researchers with a proven track record of leading an independent research group to establish or expand their research programme in India. For applicants with 7-15 years of post-PhD research experience.

Intermediate Fellowships: For postdoctoral researchers who want to establish an independent research career in India.

For applicants with 4-7 years of post-PhD research

Dr Athi Narayanan Naganathan,

Indian Institute Of Technology Madras

Dr Kalyaneswar Mandal, Indian

Institute of Chemical Biology, Kolkata

Dr Sandeepa Eswarappa, Indian Institute of Science, Bangalore

Dr Gulam Syed, Institute Of Life Sciences Bhubaneswar

experience.

Senior Fellowship

Eligibility:

Dr Rupinder Kaur, Centre for DNA



No age or nationality restrictions



A PhD in any discipline of science



The candidates need not be resident in India while

Fingerprinting and Diagnostics, Hyderabad

applying but should be willing to relocate and work

Dr Poonkuzhali Balasubramanian, Christian Medical College, Vellore

in India 

A salaried position or commitment towards a salaried position at the Host Institution is not required



Applications from Clinicians and Public health researchers will not be processed through this competition

Application forms are available on the India Alliance online application System (IASys) at

https://fellowships.wellcomedbt.org/ Login.aspx

Please visit our website for further information on the application process. Please write to us with queries to info@wellcomedbt.org

3.

UPCOMING EVENTS

SCIENCE COMMUNICATION WORKSHOPS SciComm101 workshop

Two-day SciComm workshop

23 July 2015, Jamia Millia Islamia

14-15 September 2015, Hyderabad Applications under review

For more details visit "SciComm Workshop" under "Quick Links" on our website

SciComm101 at University of Kashmir April 2015 marked one year since the launch of our one-day Science Communication (SciComm101) workshop. Since its inception, more than 700 PhD students, Postdocs, Clinicians and young faculty have been trained in research ethics, scientific writing and presentation skills. In May 2015, we conducted two SciComm101 workshops in University of Kashmir. Dr Shaida Andrabi, who invited us to conduct these workshops, writes here his views on the workshop and how it helped in reaching out to students and researchers who would otherwise not be exposed to this kind of training.

By Dr Shaida

Andrabi, Assistant Professor, Department of Biochemistry, University of Kashmir actively participate in the discussions. In our programmes, we

We are immensely grateful to the Wellcome Trust/DBT India Alliance for showing keen interest to hold the SciComm

intentionally excluded the local faculty members from the

Workshop at the University of Kashmir. This was the first time

workshop so that the students feel free during the discussions,

such a workshop was held in Kashmir. Research scholars,

especially in the topics that deal with the bioethics and

young investigators (postdoctoral fellows) and medical doctors

authorship issues. After attending the workshop, our students

(MBBS/ MD/ DM) from various institutes participated in the

and scholars felt thrilled and highly satisfied. This was a unique

workshop. We had a very good response due to which the

experience for them as most of them surely would have been

workshop was conducted for two days (11th-12th May, 2015) to

unable to attend such a programme.

By holding such kinds of high impact workshops, I believe

cover students in two groups. We had participants from the University of Kashmir, SK University of Agricultural Science and

that the India Alliance is doing a great service to the Indian

Technology (SKUAST), SK Institute of Medical Sciences (SKIMS)

Science. The vast population of the research scholars and

and the Government Medical College (GMC), Srinagar. A

scientists that work in the various Universities and institutes

total of 130 participants attended this workshop. These

across India probably never get exposed to these kinds of

workshops cover various critical aspects like the bioethics,

awareness and training programmes that are so essential for

manuscript and grant writing, presentation/ communication

their overall professional development.

It would also be sensible to engage and enable all the

skills. In addition, they also prepare the young scientists for a competitive scientific career right from the beginning of their

institutes/ universities to hold such programmes by themselves

professional training.

in the long run. The Wellcome Trust/DBT India Alliance needs to be congratulated and appreciated for conducting these

The schedule of these workshops is very well-designed.

Though these programmes run for the whole day (8-9 hrs), the

types of workshops. On behalf of the University of Kashmir, I

contents/ topics are so compact and diverse that the

thank the India Alliance team, particularly Dr Shahid Jameel,

participants do not feel exhausted or bored. The constant

Dr Madhankumar and Dr Sarah Iqbal for taking all the pains to

changes in the topics keep their minds well-focused. Another

conduct this workshop so well. I hope that the India Alliance

great aspect of the programme is that the India Alliance

team will conduct such types of workshops in Kashmir and

mentors make the students very comfortable so that they

elsewhere in the coming years as well.

4.

INDIA ALLIANCE

PUBLIC ENGAGEMENT CORNER

A dance-science interaction at the National Centre for Biological Sciences Intermediate Fellow, Dr Mukund Thattai, received the first India Alliance Public Engagement Award in 2015. Here, along with his colleagues Aparna U. Banerjee and Anjali Vaidya, he writes about his Public Engagement project ‘Bodystorming hits Bangalore’, from its conception to execution.

25 April to 2 May, 2015, working with Indian biologists and

Science is caricatured as a dry and soulless enterprise. The reality is of course far from it. Those of us who ―do‖ science

dancers to initiate new collaborations between science and

everyday know how much our work depends on imagination,

art. The interaction was the brain-child of Darius Köster, a

creativity, and accidental collisions of thought. Enter

researcher at the National Centre for Biological Sciences

―Bodystorming‖. Bodystorming means brainstorming with the

(NCBS), who first encountered bodystorming at the Marine

physical world. Creative work may be stifled if we do all our

Biological Laboratory at Woods Hole, Massachusetts in 2014. A

thinking at a desk; we think best when mind and body are

dancer himself, Darius wondered about the possibility of

integrated. In the past few years, bodystorming has been

bringing the energy of bodystorming back to India. The timing

adapted to bridge the ―two culture‖ divide between science

was perfect: in May, 2014, the Wellcome Trust / DBT India

and art by the Black Label Movement, a Minnesota-based

Alliance had just announced its first Public Engagement

dance company under the direction of Carl Flink (University of

Competition. Mukund Thattai, an India Alliance Fellow who

Minnesota), working together with biomedical engineer David

had previously organised similar art/science engagements at

Odde (University of Minnesota). Flink and Odde first used

NCBS, saw a convergence of goals: bodystorming was a

bodystorming to model violent intra-cellular dynamics, riding

unique exercise in creativity, but also a unique way to engage

off of a mutual interest in catastrophe. Each was surprised by

the public, and to spread awareness about the excitement of

the creative insights that this collaboration led to in their own

science. The Bodystorming Public Engagement proposal was

research, with Odde gaining intuitions about the effect of

successful, and in April 2015 the BLM team arrived in

―crowders‖ on chemical reactions, and Flink creating dance

Bangalore.

pieces with the BLM that drew artistic inspiration from the cell.

A key component of the Public Engagement proposal was outreach to the community of traditional and modern

Odde, Flink and eight BLM dancers (or ―movers,‖ as they

dancers across India. To achieve this, Aparna Banerjee of the

are called) spent eight event-filled days in Bangalore from

5.

INDIA ALLIANCE

PUBLIC ENGAGEMENT CORNER

NCBS Science and Society program partnered with the Antara

be started at NCBS, where scientists, dancers, and scientists

Artists‘ Collective to spread the word among the dance

with dance proclivities can continue the efforts of April's week-

community. The response was tremendous. ‗Bodystorming Hits

long residency and expand to cover new questions.

Bangalore‘ began with a weekend where BLM movers taught bodystorming techniques to 25 Indian dancers. This initial

----

training was followed by a residency at NCBS, where biologists

glycosylation, honey bee behaviour and speciation in frogs.

To find out more about this project and the various workshops that took place, visit https://bodystormingindia.wordpress.com/ http://bodystormingindia.com/

Scientists searched for insights about their systems through the

Photo credits: BLM group & Bill Cameron Photography

and dancers worked together to model systems ranging from the dynamics of virus propagation in bacterial populations to

physicality of dance, often participating in their own models.

Dancers, in turn, spent afternoons improvising on scientific structures to create art. Both products of the workshop came

Public Engagement Competition for India Alliance Fellows

together on May 2nd at the National Gallery of Modern Art (NGMA), Bangalore, as dancers showcased the human simulations and art pieces created over the past week. This

Besides its Fellowship Programme, the Wellcome Trust/DBT India

publicly-attended event presented science in an unusual and

Alliance aims to enhance the public understanding of science

very human light. The audience engaged enthusiastically with

in India. It has become increasingly important for scientists to

the performers, and went away with new insights into the

engage with the public to increase the awareness of science,

scientific process.

technology and medicine (STM) research, and themselves get fresh perspectives on their research towards a larger picture.

Several plans are now in the works to take bodystorming

To enable our Fellows to effectively and creatively engage

forward in India. Aparna Banerjee is working with Carl Flink and

with the society about biomedical science, we announced

others to create a bodystorming node in India, with a focus on

the first rolling ‗Public Engagement competition‘ in May 2014.

community engagement. One possibility is to expand

This competition is a valuable opportunity for our Fellows to

bodystorming beyond biology (for instance to economics),

showcase and share their Science with the Public and

given that bodystorming could help individuals build intuition

collaborate with other members of the society. The

for any problems involving dynamic systems. Another plan is to

engagement can be through research, social activities,

look at the potential for bodystorming as a pedagogical tool.

teaching, arts, movies/documentary and other modes of

This is a specific interest of both Aparna Banerjee, also a

knowledge sharing with the central goal of educating and

dancer and Shabari Rao, Research Artist in Residence at the

improving public awareness of science and human health

Antara Artists‘ Collective, who managed the documentation

issues. To apply, please download the application

process for this residency. Bodystorming may be one way to

form here and send the completed application form to

give students in a classroom a more visceral understanding of

public.engagement@wellcomedbt.org

complex scientific concepts. A ―bodystorming club‖ may also

6.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS Regulating delivery to the recycling center of the cell Regulation of cargo trafficking to lysosomes DR MAHAK SHARMA, Intermediate Fellow, IISER Mohali Lysosomes are membrane-bound compartments within cells of

Our findings indicate that HOPS complex regulates destruction

all eukaryotes that are dedicated to degradation of cellular

of epidermal growth factor receptor (EGFR) in lysosomes.

cargo and recycling their contents to maintain the normal

EGFR is a potent cancer-causing gene (oncogene) that drives

homeostasis of the cell. Several of these cargo molecules

tumor progression. Further, it is known that HOPS complex is

including signaling receptors or misfolded proteins if not

required for the clearance of misfolded proteins associated

degraded, can cause life-threatening diseases including

with Parkinson‘s disease. We find that a previously-reported

cancer or neurodegenerative disorders. In our recently

variant of HOPS protein, present in a small percentage of the

published research, we have described the regulation of a key

human population, cannot bind to lysosomes. It will be

protein complex that resides on lysosomes and mediates

important to study if this population has a higher risk of

delivery of cargo molecules to this recycling center of the cell.

diseases, including Parkinson‘s and cancer, that can be

This protein complex known as HOmotypic Fusion and Protein

caused due to interference with functions of lysosome.

Sorting (HOPS) complex is formed by six proteins that are conserved from yeast to humans. In this Journal of Cell Science publication, we have identified for the first time, how the human HOPS complex is targeted to lysosomes and how this

The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes.

Khatter D, Raina VB, Dwivedi D, Sindhwani A, Bahl S, Sharma M. J Cell Sci. 2015 May Image: HOPS protein subunits colocalise with small GTPase Arl8b on lysosomes in the cell

regulates function of this protein complex in trafficking.

Integrating cellular cues DR SOUMEN BASAK, Intermediate Fellow, NII, New Delhi The pleiotropic signaling pathways are

microbial agents. Our results showed that the signal integration

prevalent and are thought to impart the

via the NF-kB system reinforces pro-inflammatory cellular

capacity in mammalian cells to respond to a

responses to pathogenic cues within the intestinal niche and

variety of external stimuli. Our recent work

ensures efficient clearance of the gut-pathogen, Citrobacter

has revealed an additional biological

rodentium. These findings further suggest that aberrant

function of these pleiotropic signaling systems

signaling crosstalk via the NF-κB system may underlie the

present inside the cell, in integrating signals derived from

pathophysiology of various inflammatory disorders and

diverse cell-activating cues. In our recently published study in

autoimmune diseases.

eLife, we have identified that the integration of inflammationprovoking signals and cues from the tissue environment occurs via the so-called ―NF-kB signaling system‖, which plays a key role in coordinating immune responses against invading

7.

Stimulus-selective crosstalk via the NF-kB signaling system reinforces innate immune response to alleviate gut infection. Balaji Banoth, Budhaditya Chatterjee, Bharath Vijayaragavan, MVR. Prasad, Payel Roy, Soumen Basak. eLife 2015

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

Salmonella SUMO tussle ,

DR CV SRIKANTH Intermediate Fellow, RCB Faridabad

Acute gastroenteritis caused by the bacterium Salmonella

targeted by ST during infection to achieve this alteration.

Typhimurium (ST) is a clinical problem with significant public

Opposing the ST-mediated SUMO alteration resulted in severely

health impact. Symptoms, such as diarrhea and abdominal

compromised bacterial infection particularly affecting the

cramps, are a consequence of bacteria-mediated

intracellular life of bacteria. Furthermore, our results reveal that

inflammation, causative mechanisms of which are poorly

mechanistically Salmonella orchestrates this process by

understood. In our recently published report, we have studied

engaging small RNAs of the host. Together we demonstrate

these bacteria in an attempt to identify novel components of

SUMOylation as a novel key pathway utilised by ST for its

Salmonella-host crosstalk and endeavored to investigate an

infection and survival.

unexplored mechanism of pathogen mediated host manipulation. This mechanism, called as SUMOylation is a form of protein-modification that could drastically change the function and fate of its target. We demonstrate in cell culture

Salmonella engages host microRNAs to modulate SUMOylation: a new arsenal for intracellular survival Smriti Verma, Gayatree Mohapatra, Salman Mustafa Ahmed, Sarika Rana, Swati Jain, Jasneet Kaur Khalsa and C. V Srikanth. Molecular and Cellular Biology, June 2015.

Images: Salmonella tussle with host SUMO Cells with more SUMO show lesser bacteria and vice versa. Labeling: Salmonella labelled with red (mCherry), host-SUMOylome Yellow (Yellow fluorescent protein)

and mouse model that Salmonella infection leads to a global SUMO-conjugated proteome alteration. Our data reveals that key enzymes that participate in SUMOylation processes were

‘CLASP’ing the uptake of membrane proteins Deciphering the molecular determinants of clathrin assembly DR THOMAS PUCADYIL, Intermediate Fellow, IISER Pune

Critical aspects of cellular physiology such as cell-fate

compartments. Most membrane proteins are endocytosed

determination, self and non-self discrimination and effective

from the cell surface by a protein called clathrin, which

sensing of nutrients in the cellular microenvironment rely on

polymerises into a basket-shaped structure to bud-out a

a finely controlled display of membrane proteins on the cell

portion of the plasma membrane called the clathrin-coated

surface. The cell surface localisation of most membrane

pit. Clathrin requires a class of proteins called the clathrin-

proteins is not static but is in fact a balanced outcome of

associated sorting proteins (CLASPs) for its recruitment to the

complex trafficking pathways involving the endocytic

plasma membrane. Their ability to build a clathrin-coat around

uptake from and recycling back of membrane proteins to

the membrane is critical to the endocytic uptake of

the cell surface or their diversion to internal endolysosomal

membrane proteins. CLASPs are an evolutionarily conserved

8.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

Thus, sensitive assays that contribute to defining the molecular determinants of these early sets of interactions are critical to understanding the endocytic uptake of membrane proteins.

Epsin is a prominent member of the CLASP family and is essential for the success of clathrin-dependent endocytic uptake of membrane proteins. Our recent paper describes analysis of the intrinsic molecular properties of epsin that would help understand the cellular mechanisms by which epsin functions in clathrin-dependent endocytic pathways. Using novel biochemical and fluorescence microscopic assays with purified epsin and clathrin, we demonstrate that epsin effectively localises to membrane surfaces that are highly curved and in turn directs clathrin assembly to such regions.

Since every membrane budding event involves progressive increase in membrane curvature, these results highlight the potential role of membrane curvature in orchestrating the myriad molecular interactions necessary for the success of

http://

clathrin-mediated membrane budding. The set of biochemical assays described in our paper, which is the first to recreate clathrin polymerisation on a membrane surface, 40 years since

Cover page article

clathrin was discovered, also sets the stage for a systematic

set of adaptors that function to expand the repertoire of

analysis of the clathrin polymerisation tendency of the other

membrane proteins taken-up via the clathrin-mediated

members of the CLASP family.

endocytic pathway. Each category of CLASPs mediates the internalisation of significant classes of membrane proteins such as the G-protein coupled receptors, nutrient receptors, cell adhesion and antigen-presenting molecules. CLASPs recognise

Spatial control of epsin-induced clathrin assembly by membrane curvature Sachin S. Holkar, Sukrut C. Kamerkar and Thomas J. Pucadyil. Journal of Biological Chemistry, April, 2015

short stretches or folded domains on membrane proteins, bind specific lipids and clathrin. These interactions define the early, rate-limiting steps during the formation of clathrin-coated pits.

JBC Podcasts https://soundcloud.com/asbmb/spatial-control-of-epsininduced-clathrin-assembly-by-membrane-curvature

Since they require simultaneous lipid and protein interactions for stability, analysis of these early steps has remained elusive.

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

9.

INDIA ALLIANCE FELLOW IN SPOTLIGHT

DR FARAH ISHTIAQ Intermediate Fellow, IISc Bangalore

Dr Farah Ishtiaq is a wildlife ecologist and Wellcome Trust/DBT Intermediate Fellow at the Centre for Ecological Sciences, Indian Institute of Science, Bangalore. Her research examines the effects of infectious diseases on the ecology and evolution of birds. In this interview she talks about her research and its impact, what inspires and keeps her going everyday..

Acrocephalus dumetorum migrant in southern India

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

Malaria parasites depend on the abundance and distribution of arthropod vectors, which seem to respond sensitively to

Avian malaria is a disease caused by a protozoan parasite

temperature changes, and thereby global warming, so

infecting birds in many parts of the world. Unlike human

influencing the immunogenetics of hosts by exposing them to

malaria, to which it is closely related, it‘s not a tropical disease,

new parasites on spatio-temporal scales.

and is also found in birds in temperate regions. Most birds

In the plains, the resident birds may act as reservoirs for

survive without serious effects of the infection. However, like

blood parasites, increasing the risk that migrants will become

many diseases, malaria can be most dangerous in a host

infected with new parasites on their wintering grounds. Insects

species that has not been exposed to the disease before, and

are among the groups of organisms most likely to be affected

therefore won‘t have evolved resistance. Islands in the

by climate change, because climate has a particularly strong

Hawaiian archipelago are a classic example of how biological

direct influence on their development, reproduction, and

invasions can have a profound effect on endemic species.

survival. Given that suitable vectors are present to transmit and

These islands have been isolated from the mainland for many

maintain the infection, such migrants can form an effective

millions of years. Geographical isolation and colonisation from

bridge for parasites between wintering and breeding grounds. If

the mainland facilitated the evolution of countless unique life

the high altitude avian fauna has evolved in the absence of

forms — including, the Hawaiian honeycreepers. Avian malaria

these blood parasites, their risk of infection is potentially

and a mosquito species Culex quinquefasciatus that transmit it,

increased.

was introduced accidentally to Hawaii about a century ago,

My research focuses on the distribution of both Plasmodium

and caused big population declines and extinctions in many

and Haemoproteus blood parasites. It also investigates the

of the birds that were native to those islands, since they also

extent to which these parasites are exchanged between

had no resistance to malaria.

migrating and resident bird populations, and how the vectors that carry these parasites between hosts are expanding to new

The ultimate goal of my research is to determine the

areas in the Himalayas. The study is challenging because

influence of ecological variability, such as changes in

although we know the Western Himalayas are species-rich, the

temperature, vector community, bird migration patterns and

area is also relatively understudied, and there has been no

habitat, on the epidemiology of avian malaria and spread of

research on the dynamics of the avian diseases and their

disease in high altitude malaria-free zones. My lab is focusing

vectors to date. The findings from this research will help to

on the distribution and movement of two widespread avian

understand avian malaria transmission zones and the risk of

blood parasites Plasmodium and Haemoproteus, and by

range expansion of this disease in relation to naïve mountain

determining the extent to which Himalayan migrant birds are

birds.

exposed to these parasites in their wintering grounds.

10.

INDIA ALLIANCE FELLOW SPOTLIGHT

FARAH ISHTIAQ

biochemical and molecular biology approaches. One of the most important things that WT/DBT India Alliance funding allowed me to acquire was all the necessary equipment to set up a molecular lab and to conduct field and lab experiments which can be restrictive with many other grants. My association with this prestigious fellowship has helped to attract talented students and postdoctoral applicants to my laboratory which has further helped my research.

What keeps you going every day?

I am passionate about birds and science. My work takes me to interesting and beautiful places, teaming with birds and other wildlife. I like the fact that my research doesn‘t just involve being in a lab and processing samples. Having a field research component helps to bring important perspective to research

What inspired you to become a scientist?

questions and ideas.

I have been fascinated by nature and science since my childhood. Why there is so much diversity in life and how they co-exist, compete and evolve into new species has always fascinated me. I have been an avid birdwatcher since as an undergraduate. My passion for birds (owls in particular), science and conservation which started early when growing up in Delhi, watching wildlife documentaries, learning about long distance migration of Siberian cranes to the only wintering site in India intrigued me a lot. My father has been the strongest driving force who gently pushed me to follow my dreams to study birds and to take up wildlife ecology as career which was at that time considered as chasing a goose in the dark!! I am very glad to be able to combine both my hobby and profession which gives me the best of both worlds.

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

The Wellcome Trust/DBT India Alliance Intermediate Fellowship has played a crucial role in setting up my research

Image above (right): Mist net set up in the field (Left): Haemoporteus parasite sampled Z33653 Acrocephalus dumetorum caught in Bangalore.

program at Centre for Ecological Sciences, IISc Bangalore. I had dreamed about this research programme since my postdoctoral research. I was very pleased to be selected for Ramanujan Fellowship, which of course I declined eventually as the WT/DBT India Alliance fellowship gave me more support and flexibility. My research deals with extensive field experiments which involve mist netting of birds across

 Farah Ishtiaq, sampling birds in western Himalaya

altitudinal gradient in Himalayas and mosquito sampling. We also conduct year-round experimental field work in

Photo credits: Farah Ishtiaq

Bangalore. The generous funds from this fellowship have allowed me to set up field and lab components and to ask several important and novel questions which have never been explored in India. My laboratory uses microscopy,

Find out more about Dr Farah Ishtiaq‘s research work here

mosquito salivary glands dissections and other routine

11.

FEATURE ARTICLE

Inflamed fat cells and insulin resistance : unraveling the physiological underpinnings of the epidemic DR JOE VARGHESE, Early Career Fellow

mellitus; they remain insulin- sensitive and are metabolically

Adipose tissue (body fat) used to be considered as an inert energy store. The very appearance of a fat cell, adipocyte,

healthy, despite increased body weight (4). Morbidly obese

with its large lipid globule occupying most of its volume,

individuals who have undergone bariatric surgery have

minimal amounts of cytoplasm and a nucleus isolated to the

remarkably improved insulin sensitivity that precedes significant

periphery of the cell, gives it the most innocuous look.

weight reduction (5). It therefore appears that adipose tissue

However, it is now known that adipose tissue is a metabolically

per se does not directly induce insulin resistance.

active organ with multiple endocrine functions that can Research over the last decade or so has shown that

influence whole-body metabolism in many ways. Recent research has focused on the adipose tissue as the key agent

inflammatory events in adipose tissue, especially in the visceral

behind the development of insulin resistance and diabetes

adipose depots, play an important role in the development of

mellitus (1).

insulin resistance. As fat accumulates, the adipose tissue undergoes a remodeling process that promotes local

The problem of obesity has grown to epidemic proportions

inflammation. A significant proportion of cells (up to 40%) in the

over the last several decades with changing lifestyles and food

visceral adipose tissue of obese patients with diabetes mellitus

habits. More than 50% of the population in the western world is

consist of infiltrating immune cells, chiefly macrophages. These

either overweight or obese (2). Reliable data from India is

macrophages are activated and have a pro-inflammatory

unavailable; however, even by conservative estimates, it is

(M1) phenotype. They secrete cytokines, such as tumor

believed that obesity contributes significantly to morbidity and

necrosis factor alpha (TNFÎą) and other inflammation mediators

mortality in the general population. Obesity puts an individual

that induce a state of chronic low-grade inflammation in the

at high risk for many disease conditions; diabetes mellitus,

adipose tissue (6). These mediators, not only induce the

coronary artery disease, hypertension, stroke, cancer and

infiltration of more immune cells into the adipose tissue, but

osteoarthritis are some examples. It is by far the most important

also re-program the adipocytes to stimulate fat breakdown, a

risk factor for diabetes mellitus. A number of studies have

process called lipolysis. Consequently, lipids stored as

shown a strong association between the body mass index

triglycerides are broken down to release free fatty acids (FFA).

(BMI) and insulin resistance, the hallmark of type 2 diabetes

A number of studies have directly implicated increased blood

mellitus (3).

FFA in mediating resistance to the actions of insulin in tissues like the skeletal muscle and the liver (7,8). Insulin is the chief hormone that inhibits lipolysis in the adipose tissue. Therefore,

Insulin resistance refers to the impaired ability of the body to respond to insulin by reducing blood glucose levels. Tissues

the development of insulin resistance, under these

such as adipose tissue and skeletal muscle, are unable to take

circumstances, contributes to a vicious cycle where lipolysis

up glucose from the blood under these conditions, resulting in

induces insulin resistance which in turn exacerbates lipolysis.

increased blood glucose levels (hyperglycemia).

The adipose tissue secretes a large number of hormones

Hyperglycemia triggers several biochemical events that ultimately result in chronic complications of diabetes, such as

(called adipokines) that can greatly influence metabolism and

nephropathy, retinopathy and neuropathy.

nutrient homeostasis. Among these, adiponectin and leptin have been extensively investigated. Adiponectin has anti-

Although it is known that a strong association exists between

diabetic effects and increases insulin sensitivity in the liver and

obesity and insulin resistance, the exact molecular

muscle. Leptin, on the other hand, modulates energy

mechanisms involved are not precisely clear. A significant

homeostasis by regulating food intake and energy

proportion of obese individuals do not develop diabetes

expenditure. More adipokines, such as resistin and visfatin, have been discovered more recently.

12.

FEATURE ARTICLE

Inflamed fat cells and insulin resistance : unraveling the physiological

underpinnings of the epidemic

Their roles in the pathogenesis of insulin resistance are currently

play in the pathogenesis of insulin resistance and diabetes

being investigated (9). Adipose tissue inflammation can

mellitus. Therapeutic modalities that are aimed at ameliorating

modulate the synthesis and secretion of these adipokines,

adipose tissue inflammation and/or inhibiting lipolysis may be

possibly mediating, at least in part, the effects of adipose tissue

promising new drug targets to help fight the obesity and

inflammation on insulin sensitivity in the liver and muscle (10).

diabetes epidemics.

References:

Insulin resistance and obesity are also associated with changes in iron homeostasis in the body, especially in the adipose tissue. A number of large epidemiological studies have documented the observation that raised serum ferritin levels are consistently associated with an increased risk of developing diabetes mellitus (11). Serum ferritin levels are often used as an indicator of body iron stores; however, high levels are also associated with inflammatory conditions. It is not clearly known whether the raised ferritin levels seen in association with insulin resistance is caused by increased body iron stores or due to the inflammation associated with obesity.

Nevertheless, there is evidence to suggest that increased body iron stores play a role in the pathogenesis of insulin resistance (12,13). Increased iron levels in adipocytes have been shown to induce insulin resistance by initiating local inflammation and modulating the secretion of adipokines, especially adiponectin (14). The yet to be published findings from my research, funded by the India Alliance, show that increased intracellular iron can directly inhibit insulin signaling and induce insulin resistance in hepatocytes. The current research in my laboratory is aimed at systematically documenting the changes in iron homeostasis that accompanies development of insulin resistance. The ultimate aim of these studies is to understand the role played

1. Johnson AMF, Olefsky JM. The origins and drivers of insulin resistance.

Cell. 2013 Feb 14;152(4):673–84.

2. WHO | Obesity [Internet]. [cited 2015 Jun 27]. Available from: http://www.who.int/gho/ncd/risk_factors/obesity_text/en/ 3. Twig G, Afek A, Derazne E, Tzur D, Cukierman-Yaffe T, Gerstein HC, et al. Diabetes risk among overweight and obese metabolically healthy young adults. Diabetes Care. 2014 Nov;37(11):2989–95.

4. Primeau V, Coderre L, Karelis AD, Brochu M, Lavoie M-E, Messier V, et al. Characterizing the profile of obese patients who are metabolically healthy. Int J Obes (Lond). 2011 Jul;35(7):971–81.

5. Wickremesekera K, Miller G, Naotunne TD, Knowles G, Stubbs RS. Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obes Surg. 2005 Apr;15(4):474–81.

6. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesityrelated insulin resistance. J Clin Invest. 2003 Dec;112(12):1821–30.

7. Perry RJ, Camporez J-PG, Kursawe R, Titchenell PM, Zhang D, Perry CJ, et al. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell. 2015 Feb 12;160(4):745–58.

8. Rachek LI. Free fatty acids and skeletal muscle insulin resistance. Prog Mol Biol Transl Sci. 2014;121:267–92.

9. Antuna-Puente B, Feve B, Fellahi S, Bastard J-P. Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab. 2008 Feb;34(1):2–11.

10. Ohashi K, Yuasa D, Shibata R, Murohara T, Ouchi N. Adiponectin as a Target in Obesity-related Inflammatory State. Endocr Metab Immune Disord Drug Targets. 2015;15(2):145–50.

11. Simcox JA, McClain DA. Iron and Diabetes Risk. Cell Metabolism. 2013 Mar 5;17(3):329–41.

12. Jiang R, Manson JE, Meigs JB, Ma J, Rifai N, Hu FB. Body iron stores in relation to risk of type 2 diabetes in apparently healthy women. JAMA. 2004 Feb 11;291(6):711–7.

13. Fernández-Real JM, Peñarroja G, Castro A, García-Bragado F, Hernández-Aguado I, Ricart W. Blood letting in high-ferritin type 2 diabetes: effects on insulin sensitivity and beta-cell function. Diabetes.

2002 Apr;51(4):1000–4.

14. Gabrielsen JS, Gao Y, Simcox JA, Huang J, Thorup D, Jones D, et al.

Adipocyte iron regulates adiponectin and insulin sensitivity. J Clin Invest.

2012 Oct 1;122(10):3529–40.

by iron in initiating and/or exacerbating insulin resistance associated with obesity.

The way forward for research in this area is to identify

Dr Joe Varghese is Wellcome

mechanisms that trigger inflammation in the adipose tissue in

Trust/DBT India Alliance Early Career Fellow based at CMC, Vellore. He is involved in studies on dysregulation of iron metabolism associated with alcoholic liver disease and insulin resistance.

Apart from research he has special interest in teaching undergraduate and postgraduate students basics of ethical academic/ research writing. Find out more about his research here.

obese individuals. Drugs that inhibit lipolysis may preserve insulin sensitivity at the cost of increasing body weight.

Mechanisms that can decrease free fatty acid (FFA) levels are also likely to improve insulin sensitivity. Aerobic exercise reduces body weight and also increases the ability of the body to use free fatty acids as a source of energy, thus decreasing its levels in the blood. These events may underlie the wellknown phenomenon of improved insulin sensitivity with exercise.

Image Credit David Gregory&Debbie Marshall, Wellcome Images Adipose tissue, close-up showing adipocytes, SEM Scanning electron micrograph of adipose tissue, showing adipocytes. Computer-coloured orange. Scanning electron micrograph 2003

In conclusion, adipose tissue metabolism and its role in regulating nutrient homeostasis may have a central role to

13.

IN CONVERSATION WITH..

Prof Shankar Balasubramanian Professor Shankar Balasubramanian is the Herchel Smith Professor of Medicinal Chemistry at University of Cambridge, co-inventor of a genome sequencing technology and co-founder of Solexa. His research is focused on elucidating the chemistry, structure and function of DNA and RNA. He was the fourth and last speaker of our DNA@70 Public Lecture series.

DNA Quadruplex Model. Credit Prof Balasubramanian

Could you briefly take us through your scientific journey so far?

Potential of genome sequencing technologies in tackling human health issues is immense but what do you see as the real challenges in this field?

I studied Natural Sciences as an Undergraduate in Cambridge University (1985-88). Whilst I ultimately specialised in chemistry,

There are challenges in the adoption of genomic approaches

this broad science curriculum helped stimulate my interests

to human health. Some of these will require a change in

throughout the sciences. I pursued a PhD in Cambridge (1988-

culture both in society and in the way we practice

1991), under the supervision of Chris Abell, in which I studied

medicine. Whilst there are emerging examples of how

the chemical reaction mechanism of an enzyme in detail. I

genomic sequencing has provided important, and sometimes

then pursued a postdoc in the lab of Stephen Benkovic at the

actionable, insights in clinical cases in rare genetic disorders or

Pennsylvania State University (1991-1993). This was a

certain cancer sub-types, population scale sequencing in

stimulating interdisciplinary laboratory where I learned to

clinical settings is required to fully unlock and understand the

combine chemistry, molecular biology and physical methods

potential of genomic medicine. As population scale

to study the structure and function of several medically

sequencing has really only just begun, we need to allow at

important enzymes. I began my independent research career

least another decade and resist passing judgment on what is

in 1994 in the Department of Chemistry, Cambridge University,

possible prematurely. There is also a need to build the

initially working on solid phase organic synthesis before moving

information architecture to optimally link genomic information

onto the study of nucleic acids chemistry and biology. It was

with clinical information (immediate and longitudinal) in a form

during the course of fundamental single molecule

that is of practical use to drug discoverer/developers and

fluorescence experiments on the synthesis of DNA by a DNA

ultimately doctors and their patients.

polymerase that my collaborator David Klenerman and I conceived the ideas that ultimately led to Solexa sequencing

What is the best advice you have ever received?

that we commercialised via our start-up company Solexa, formed in 1998. For the last decade or so my lab has focused

Pursue your own path.

on discovering and elucidating dynamic structural and chemical features that naturally occur in DNA and/or RNA

Your message for young students and researchers.

such as G-quadruplex structures and covalent base modifications. I believe there is much that remains to be discovered and understood about the structure(s), chemistry

Seek out and address questions that may provide interesting

and function(s) of nucleic acids. This is what I will be continuing

and important insights. Only work on something that you find

to pursue in my research over the next decade.

highly stimulating.

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

I actually wanted to be a professional footballer until I was17

Find out more about Prof Balasubramanian’s research here.

and turned to science (I didn't make the cut with football....).

14.

VIEWPOINT

What is good science and when do you know you’re doing it?

DR ARUN SRIPATI, Intermediate Fellow

I have had the good fortune of working with or knowing

It has no doubt been extremely challenging to start a new lab, but I find myself surprised to admit that the external

several excellent scientists. They have wholeheartedly gone

challenges pale before a rather perplexing inner question:

after whatever questions they found interesting without regard

what is good science, and when do you know you’re doing it?

to importance. Very frequently they do not fulfill the proxy criteria but they are highly regarded by their peers. They are excellent teachers. They remain focused on their science

The question is rather perplexing because there are a bewildering number of proxy answers which have gained

despite all the distractions that are part and parcel of the job.

great traction with peers and funding agencies alike. Consider

They are devoted to the pursuit of the truth. But above all, their

a few: you‘re doing good science if (1) you are publishing in

defining characteristic is that they approach science with a

Nature and Science; (2) your work has a high impact factor;

child-like enthusiasm and wonder. I was once at a lunch table

(3) you are successful in getting grants; (4) you have lots of

with the eminent neuroscientist Vernon Mountcastle who was

students and post-docs. While successful scientists often qualify

then in his nineties. He grasped a paper cup with his hands

on all these counts, the reverse is not true: qualifying on these

and marveled at how our hand senses the weight of the cup

counts does not guarantee that you are doing good science.

and lifts it with just the right amount of force. It was

We all know spectacular examples from this category, but at

immediately clear why he was such a great scientist.

the same time it is hard to resist measuring ourselves using Perhaps these internal qualities do not guarantee that you

these criteria.

are doing good science just like the external criteria do not, but there is one important difference. Achieving single-minded

But leave aside these proxy answers. This question is perplexing at a more fundamental level. As an independent

concentration, child-like wonder and the pursuit of truth

investigator you become aware of several open scientific

without regard to its consequences are almost spiritual qualities

problems from which you choose a few to work on given your

that seem as close to a guarantee as anything that you will do

resources and expertise. For a few problems you immediately

good science. Plus, for free, they give you an inner peace in a

know their worth. But most of them are hard to assess – will your

way that no impact factor can.

results be important or incremental? Will your experiments reveal something novel or will they always be hypothesisdriven? Are your experiments addressing important questions in

Dr Arun Sripati is Wellcome Trust/DBT

the field? It is very easy to be deluded into thinking that your

India Alliance Intermediate Fellow based at the Indian Institute of Science, Bangalore. Visit his lab website to find out about his research.

experiments are the most important ones. Separating truth from self-delusion can be extremely hard - and this is the sort of crucial feedback and mentoring missing in the system for younger investigators.

15.

INDIA ALLIANCE STAFF CORNER

DR DIPANWITA SENGUPTA, Grants Adviser

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..

Image credit www.rabindrasangeet.org/

scientists who are associated with the organisation either as a

What is your background?

Committee member or a Fellow. As a team, we share work, we

My ancestors were affected by the partition of Bengal. With

share jokes and we also share interesting news in science. The

the inspiring stories of their struggle to re-establish themselves

transition from a research laboratory to the position of a Grants

starting from nothing, my childhood possession included a

Adviser was not very smooth for me. This organisation and its

photograph of my grandparents with other family members in

people have been with me through this important phase of my

front of the ancestral house, which I could never visit. I grew up

life.

in a small town in West Bengal. My father worked in the steel plant in Durgapur and we lived in the industrial township.

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

Looking back, I remember that caring for puppies of stray dogs was the most favourite game between my younger sister and

If this question was asked a year before, I would have said

me. When it was time to look for courses in colleges I found

music and reading Bengali literature. These days, when not

very limited opportunity there but influenced by a few friends,

busy being a Grants Adviser, I am busy playing with my little

travelled across the country to study in Maharashtra. I stayed in

daughter, Dripta. She has somehow overshadowed all my

Aurangabad for 5 years to complete by BSc and MSc in

other likings and keeps me occupied completely. At the end

Microbiology. Soon after completing my masters, I started

of the day I feel happy, content and of course very tired.

applying for PhD positions and got a call from Professor S K Sen

During my childhood, every evening music classes were held

of IIT Kharagpur. I visited his laboratory and subsequently joined

at our home. In addition to being a great home-maker, my

his group. The project was based on a fermentation

mother spent many years receiving training in and teaching

technology and I was happy to be surrounded with plates of a

Rabindra Sangeet and Hindustani classical music. Though I was

lot of colourful and some not so colourful bacterial colonies

forced to get formal training, I did not involve myself seriously

and biochemical assays. I went to Virginia Commonwealth

at that time. I thought that it would be wise to choose

University for my postdoctoral studies. The host pathogen

academics and not waste my time practising music. But it was

relationship of a dental pathogen and a diverse environment

only when I went to college that I realised that you can make

and culture are some cherishing lessons of my life. I also

quite a lot of admiring friends and connect with many people

worked at the Centre for Cellular and Molecular Biology,

through music. My hobbies include listening to soothing

Hyderabad for some time before joining the India Alliance as a

melodies, accompanying my husband in his culinary

Grants Adviser.

adventures and spending time with our friends.

How has your India Alliance journey been so far?

Who inspires you (living or dead)?

It‘s a long list. In addition to my parents and my little one, I am

I feel that the best part about working at the India Alliance is

inspired by Netaji Subhash Chandra Bose and Rabindranath

being able to be in touch with a small but brilliant team every

Tagore.

day and having the opportunity to meet some renowned

16.

EXTERNAL EVENTS

India Session at 6th EMBO meeting 2015, Birmingham, UK 5-8 September, 2015 The India Alliance is organising a joint session in association with IndiaBioscience at the 6th EMBO meeting 2015, Birmingham, UK on 7th September 2015. If you are planning to attend this meeting, please join us at the India Session: Life Sciences opportunities in India to find out about setting up your laboratory in India, or moving to India for a post-doc.

We are offering travel awards to attend the EMBO meeting.

These awards are available to PhD students, Postdocs and Young Investigators to cover travel expenses. To qualify for the travel award, an applicant must be an Indian national based in India or Europe and he/she must be the first author on the abstract. To apply, click here. Deadline for submitting applications is 15 July 2015.

17th International Congress on Infectious Diseases, Hyderabad, India 2-5 March 2016 The 17th ICID will encompass all of the fields of infectious diseases with particular attention being paid to the major challenges of the region including AIDS, malaria, tuberculosis, pneumonia and enteric infections including typhoid fever and diarrhea. In addition, major areas of neglected tropical diseases will be discussed and there will be a particular focus on disease prevention and vaccination.

One of the things that distinguishes ISID meetings is the unique blend of state-of-the-art scientific presentations that encompass both basic science and clinical practice, delivered by a truly international faculty who uniquely have the hands on experience and knowledge of the conditions that they discuss. The ISID meetings are also notable for their representation from an extraordinarily wide range of countries, and the opportunity for close exchange and communication between the most senior and more junior colleagues. http://www.isid.org/icid/index.shtml

17.

EXTERNAL EVENTS

As a part of ‗Workshop Series 2015-2016‘ IIPH-D is inviting applications for the following workshops: Title: Leadership in Health and Development Sectors Date: July 21 – 24, 2015 Last date of registration: July 15, 2015 Title: Workshop on Data Management using CSPro Date: July 28 - 31, 2015 Last date of registration: July 14, 2015 Title: Effective Behaviour Change Communication Strategies in Public Health Date: August 3 - 7, 2015 Last date of registration: July 20, 2015 Title: Nutritional Management of Children with Severe Acute Malnutrition (SAM) Date: August 17 - 21, 2015 Last date of registration: August 3, 2015 Title: Economic Evaluation of Health Care Programmes Date: August 25 - 28, 2015 Last date of registration: August 11, 2015 To view complete brochure click here:-Workshop Series 2015-2016 (IIPH- Delhi)

Cover image in this issue: Great Tit (Parus major) widely distributed in India Image credit: Dr Farah Ishtiaq

Erratum: Cover and issue image in May 2015 issue showed immunohistochemical staining in prostate cancer tissue for SPINK1 and not ERG as was mentioned in its description.

Please send your feedback, suggestions and contributions to public.engagement@wellcomedbt.org Follow us on 18.