India Alliance Newsletter I Issue 20 I March 2018

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News & Views Issue 20 March 2018


EDITORIAL Welcome to the second India Alliance newsletter issue of 2018. This issue is filled with exciting research from our Fellows’ research groups on diverse range of topics, updates on India Alliance’s new initiatives aimed at strengthening research ecosystems in India, and various events held over the last two months.

In the last two months, India Alliance has organized one-day Science Communication workshops at Bhabha Atomic Research Centre (BARC), Mumbai, Pondicherry University and Ahmedabad University. These workshops were attended by more than 150 Masters students, PhD scholars and junior faculty.

At the start, we would like to extend our heartiest felicitations and best wishes to Prof. Vijay Raghavan, Former Secretary, Department of Biotechnology, Government of India, for his appointment as the Scientific Advisor to the Indian Government. We are very pleased to share that India Alliance Margdarshi Fellow Prof. Sandhya Vishweshwaraiah (IISc, Bangalore) has been elected into the World Academy of Sciences. Early Career Fellow and Assistant Professor at IIT Bombay, Dr. Abhijit Majumder has been selected as a member of Global Young Academy. Dr. Arun Shukla, Intermediate Fellow at IIT Kanpur, is the co-recipient of CDRI Award for Excellence in Drug Research 2018 in Life Sciences. Many congratulations to them! We are presently not accepting applications for any of our Fellowship schemes. Check our website for regular updates on our various funding schemes. As always, it is a pleasure to bring to you a diverse mix of recently published research of our Fellows in the Research Highlights section. Dr. Sam Mathew and his team at RCB Faridabad have identified new role of a protein that regulates the function of MET, a cancercausing gene, in the development of cancer of the skeletal soft tissue. Insights from this study might help develop better cancer treatment strategies for deadly childhood cancers of the muscle such as Rhabdomyosarcoma. Recently published research from Dr. Ravi Manjithaya’s group at JNCASR, Bangalore, adds to our understanding of autophagy, the process of cleaning unwanted junk from the cell. Additionally, their research has identified novel drugs that target autophagy pathways and will now be tested in clinically-relevant systems. Dr. Deepa Subramanyam and colleagues at NCCS Pune have revealed that intracellular trafficking machinery in stem cells can bring about changes in cell fate. Latest research from Dr. Rupinder Kaur’s lab at CDFD Hyderabad shows a novel role for a family of proteins present in the cell wall of a pathogenic yeast that helps it survive in the human host. Dr. Aparna Rao based at LV Prasad Eye Institute, Bhubaneswar, and her colleagues identify molecular markers for pseudoexfoliation, a unique eye disease which is associated with “dandruff-like” flaky deposits in the eye, that uncover its association with glaucoma.

India Alliance organized Science Policy session at the International Congress of Cell Biology (ICCB2018) on 31 January 2018. This event, moderated by Dr. Shahid Jameel, CEO, India Alliance, brought together prominent researchers from India and overseas to address the opportunities and challenges for Life Sciences research in India, and to discuss the way forward. India Alliance, in partnership with IndiaBioscience, also organized Careers in Science event at the ICCB2018 on 1 February 2018. This event was aimed at raising awareness among young researchers about the various career opportunities available for science graduates and arm them with the tools to make the right career choices. Details of this event are included in this issue. The report and recommendations from the Women in Science – A Listening Session which was jointly organized by the India Alliance and the US Embassy, New Delhi, in November 2017, was released by the Hon'ble Union Minister for Science & Technology & Earth Sciences, Dr. Harsh Vardhan, at the "National Conference on Technological Empowerment of Women, organised by National Academy of Sciences, India (NASI), on 8 March 2018. Link to the full report included in this issue. In the Public Engagement section, read about the recently held Public Health Theatre Festival in Ahmedabad that was organised by Darpana Academy of Performing Arts as part of the public engagement project the Actor Doctor Theatre project to foster cross-disciplinary exploration of health. Also, find in this issue, interview of Dr. Shahid Jameel (CEO, India Alliance) and Dr. Savita Ayyar (Lead, IRMI) where they talk about IA’s recent initiative, India Research Management Initiative (IRMI) which aims to strengthen institutional ecosystems and provide a mechanism for enabling research management at institutions in India. Finally, India Alliance launched another significant initiative, AfricaIndia Mobility Fund (AIMF) to promote cross-learning and collaboration between India and African biomedical researchers. More information on this funding has been included in this issue. As always, a huge thank you to all those who have contributed to this newsletter. Special thanks to Dr. Sucharita Sambashivaiah for sharing the cover image which shows a cross section of normal human skeletal muscle fibers.

Anusha Krishnan writes about Prof. Raghu Padinjat (NCBS, Bangalore) and his team’s latest research that provides a new twist to an old story of cellular signaling in the eye of a fly.

As always, it’s helpful to receive your valuable comments and suggestions for the newsletter so make sure you keep them coming.

This issue also includes interview of our Intermediate Fellow Dr. Sucharita Sambashivaiah, based at St John’s Medical College, Bangalore, and profiles of new Fellows.

Find archives of our past newsletters here.

The second Developing Indian Physician Scientist (DIPS) workshop was held from 4-7 March at CCMB, Hyderabad. These workshops facilitated by IA Fellow, Dr. Anurag Agrawal (CSIR-IGIB, New Delhi) and Dr. Rakesh Aggarwal (SGPGI, Lucknow), aim to ignite scientific curiosity in young doctors, while promoting an understanding of the frontiers of medicine and related sciences. Visit our website to find out more about these workshops.

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Sarah Hyder Iqbal, PhD Public Engagement Officer Wellcome Trust/DBT India Alliance March 2018


CONTENT

4 New India Alliance Fellows 12 India Alliance Fellow in Spotlight Interview with Sucharita Sambashivaiah , St. John’s Medical College, Bangalore

14 India Alliance workshops & events * 2nd Developing Indian Physician Scientist (DIPS) workshop, Hyderabad * Science Communication workshops * India Alliance at ICCB2018 – Science Policy session & Careers in Science workshop

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Public Engagement *Actor and Doctor – Public Health Theatre Festival * Women in Science

20 New initiatives * India Research Management Initiative * Africa-India Mobility Fund

22 India Alliance Staff Corner Dr. Shingar Sharma, Grants Adviser

23 Other announcements *NEXUS Startup Hub

CARB-X – Call for applications 2019 Fulbright Fellowship- Call for applications Hamied Foundation UK-India AMR Visiting Professorships

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NEW

INDIA ALLIANCE FELLOWS

INTERMEDIATE FELLOW 2017

EARLY CAREER FELLOWS 2017

Basic Biomedical Research Fellowships

Basic Biomedical Research Fellowships

Investigating mechanisms underlying adaptation and virulence of pathogenic bacteria, Staphylococcus aureus

Understanding the role of RNAi-mediated antiviral host defense against DNA viruses Dr. Jyoti Singh

Dr. Geeta Ram

National Centre for Cell Science, Pune

Regional Centre for Biotechnology, Faridabad

WEBSITE

WEBSITE

Insects lack adaptive immunity yet can combat viral infection most effectively. Recently, it has become evident that RNA interference (RNAi) plays a key role in antiviral defense mechanism in insects. RNAi is a small non-coding RNA-mediated post-transcriptional gene silencing mechanism. In insects, our knowledge about RNAimediated antiviral defense is mainly confined to RNA viruses. DNA viruses have hardly been the subjects of such investigations, except for few recent reports. To comprehend the role of RNAi in antiviral defense against DNA viruses, we have selected an insectvirus model system comprising the domesticated silkworm, Bombyx mori, and its natural pathogen, Bombyx mori nucleopolyhedrosis virus (BmNPV), which is a double-stranded DNA virus. Different strains of silkworm display a high degree of variation with regards to their tolerance against BmNPV, which provides a powerful tool to understand viral tropism and evolution of intricate insect-viral interactions. Using this insect-virus model, we are interested in addressing the some of the important questions of antiviral RNAi against DNA viruses such as: What are the key components of RNAi that participate in DNA virus infection? Does RNAi regulate other innate immune responses? Do cellular miRNAs inhibit virus infection by targeting viral transcripts? Can cellular small ncRNA signatures be used as a genetic marker against viral infection?

Staphylococcus aureus (S. aureus) is a pathogenic bacterium that can infect any organ of the human body. It’s one of the most successful pathogens, having remarkable adaptability and virulence. S. aureus strains can carry different mobile genetic elements (MGEs), including plasmids, transposons, staphylococcus cassette chromosomes (SCC), bacteriophages and staphylococcal pathogenicity islands (SaPIs), which contribute to their virulence, broad host range and antibiotic resistance. Horizontal transfer of MGEs among different S. aureus strains plays a vital role in the evolution of this pathogen. SaPIs are highly mobile chromosomal islands that are induced to excise and replicate by specific phages, “helper phages”. The SaPI replicated DNA is packaged in phage-encoded particles and released upon phage-mediated lysis. These islands, often carry unique toxin genes, move readily between strains, mediate transfer of unlinked chromosomal genes and interfere with the reproduction of the very phages they parasitize. All sequenced genomes of naturally occurring staphylococcal strains contain at least one intact or defective SaPI. I propose that the diversity, adaptability and virulence of this notorious pathogen depend greatly on its extraordinary islands (SaPIs). The focus of my research proposal is these incredible islands. An understanding of their biology and capabilities will enable us to modify the SaPI and consequently reduce the severity and spread of staphylococcal infection. The proposed research focuses on SaPI’s complex role in HGT, in staphylococcal genomic plasticity and in the metamorphosis of this infamous pathogen.

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NEW

INDIA ALLIANCE FELLOWS ensemble measurement of millions of cells together can provide average information. For example, any omics analysis in bulk population is informative, however it is not enough to understand detail about cellular heterogeneity characteristics and molecular dynamics. The conventional cellular characteristics can provide high percentage of cell death and nonuniform transfection by using any chemical and physical methods, which are unable to characterize cellular function precisely. On the other hand uniform single cell intracellular transfection is an important mean in cell biology and therapeutic development. From last decade single cell phtoporation platform came into frontier research for high efficient intracellular delivery. However, none of the techniques can provide precise uniform delivery into single cells and their throughputs are very limited. Here, we proposeed BioMEMS based compact, easy to use, massively parallel, high throughput single cell photoporation platform, that can overcome the throughput limitation as well as it can provide precise uniform single cell intracellular transfection with controllable light pulses to achieve high efficiency and high cell viability. The device potentially applicable for single cell therapy and diagnostics. Our Laboratory mainly focuses on research about Bio-MEMS/BioNEMS devices based single cell therapy and diagnostics using different physical methods such as nano-electroporation, photoporation, mechanoporation, thermoporation, magnetoporation and etc.

Investigating aberrant Tumour Protein 53 regulation in Acute Lymphoblastic Leukaemia (ALL) Dr. Pritha Paul Tata Translational Cancer Research Centre (TTCRC), Tata Medical Center, Kolkata WEBSITE

TP53 alterations are present in about 2-3% of children with acute lymphoblastic leukaemia (ALL) at initial diagnosis, but increases to ~13-15% at relapse and have been identified as the most significant subclonal mutation associated with recurrent therapeutic failure in ALL. These patients most often relapse early on-therapy. Another group of patients with similar clinical phenotype of early relapses, despite wild-type TP53, supports our hypothesis that common aberrant signalling pathways regulated either epigenetically in TP53 wild-type or by gain-of-function in TP53 altered ALL cells have an unexplored role in therapeutic failure. In addition, recent publications have offered insights into how the microenvironment influences cancer cell behavior and in turn is influenced by the cancer cells to create a favorable niche. One of our recent works has demonstrated how leukaemic cells can modulate the behavior of bone marrow stromal cells (BMSCs) resulting in altered mitochondrial metabolism in these stromal cells. p53 signaling pathways play a critical role in maintaining homeostasis of cells, especially with respect to mitochondrial metabolism and redox adaptation. We are yet to understand how the bone marrow stromal cells influence leukaemic cells with dysregulated p53 signaling or when harbouring TP53 alterations.

Understanding the regulatory role of G-quadruplex in modulating gene expression in Mycobacterium tuberculosis (Mtb) Dr. Kushi Anand IISc Bangalore WEBSITE

Massively Parallel High Throughput Single Cell Intracellular Delivery Using Light Pulses

G-quadruplex (G4) is non-canonical secondary structure. These motifs are formed naturally in nucleic acid by sequences that are rich in G’s. Genomes of diverse organisms contain G4 motifs, which are important in regulating multiple biological functions such as transcription, genomic stability, and stress resistance. Owing to the regulatory role of G4, they are known to modulate cancer progression and other pathogenic infections such as malaria. Moreover, targeting G4 is actively under consideration for cancer therapy. Interestingly, genome of one of the most successful human pathogen Mycobacterium tuberculosis (Mtb) is 65%GC-rich. It is also known that Mtb has an unusual capacity to adapt under diverse environmental conditions by changing gene expression for its survival during infection. However, we lack clear knowledge of mechanisms responsible for coordinating gene expression under various growth conditions in Mtb. Our in-silico analysis revealed that ~ 30% of Mtb genes contain putative G4 forming motifs in their regulatory regions, indicating that G4 sequences might play an important in regulating expression. Despite this, so far there is no study on understanding the role of G4 motifs in this difficultto-track intracellular pathogen. Therefore, our aim is to systematically dissect G4 mediated regulation in Mtb.

Dr. Tuhin Subhra Santra Indian Institute of Technology (IIT) Madras, Chennai WEBSITE

Cells are the most fundamental building block in our day to day life. However cells to cells or cells to environment interaction are still unknown. To understand cellular interaction with each other

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NEW

INDIA ALLIANCE FELLOWS

Understanding these mechanisms will shed new light on the basic biology of Mtb and also on how this pathogen survives in response to various stress conditions. Results from such a comprehensive study will not only deepen our understanding of previously uncharacterized relation between functionally important G4 and virulence in Mtb but also open up new avenues of fundamental and translational researches, which will most likely aid in better tuberculosis management.

Understanding the influence of inflammatory cells on bone cells in Rheumatoid Arthritis Dr. Sushmita Chakraborty All India Institute of Medical Sciences (AIIMS), New Delhi

Longitudinal assessment of retinal structure and function in diabetes with and without retinopathy

WEBSITE

Inflammation is central to the pathogenesis of RA and inflammatory cytokines are therefore attractive therapeutic targets for RA. Over the past two decades, several cytokines have been implicated in the pathogenesis of RA and tested for their therapeutic potential. Biologics targeting the key inflammatory cytokines are already approved for therapeutic use in RA but are associated with several side effects that make their persistent administration concerning. Moreover, in RA sustained treatmentfree remission is rarely observed with biologics. Therefore, understanding RA pathogenesis is extremely essential for the search of newer inflammatory molecules for eventual delineation of therapeutic targets. My current research in RA is focused towards understanding following aspects: 1) how cytokines are positioned in the complex cytokine network in synovial inflammation? 2) How to boost self tolerance. 3) How immune cells and their mediators influence bone homeostasis? 4) Cross talk between immune and bone cells.

Dr. Sangeetha Srinivasan

Vision Research Foundation, Chennai WEBSITE

The overall aim of my work is to employ non-invasive and reiterative ophthalmic techniques – to characterize longitudinal changes in retinal integrity in patients with diabetes, with and without diabetic retinopathy (DR). The study complements the research agenda of the Host Institute wherein, a population-based study (Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular genetics Study-SNDREAMS) was conducted between the years 2003-2010. The SNDREAMS study estimated the prevalence of diabetes and diabetic retinopathy in urban Chennai, South India, and also elucidated the clinical, anthropometric, biochemical and genetic risk factors associated with diabetic retinopathy. For the study pertaining to my fellowship, I utilize a combination of retinal structural and functional measures to address my research agenda. This particular work is not only timely but is much needed especially for the Indian population where diabetes is increasing at an alarming rate. Despite reasonable control of the systemic risk factors, some individuals continue to develop or show worsening of DR. This 5-year longitudinal study holds promise to unravel novel ophthalmic “markers� to characterize for the first time, those patients who are at risk of visual loss. It is hoped that the study outcomes would have important contributions to patient care.

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INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS A novel mechanism underlying Rhabdomyosarcoma, a type of childhood cancer of the soft tissue Dr. Sam Mathew, Intermediate Fellow Regional Centre for Biotechnology (RCB), Faridabad Recent research from our group identifies role of a protein that regulates the function of MET, a cancer-causing gene, in the development of cancer of the skeletal soft tissue. Insights from this study might help develop better cancer treatment strategies for deadly childhood cancers of the muscle such as Rhabdomyosarcoma. Rhabdomyosarcoma is a cancer which occurs mostly in children, accounting for about 3% of all childhood cancers. Rhabdomyosarcoma generally develops in the muscles around the bone that are responsible for movement and slowly spreads to other parts of the body. Rhabdomyosarcoma tumor cells exhibit several similarities to developing muscle cells, including expression of muscle differentiation proteins such as MyoD, Myogenin and myosin heavy chains. However, rhabdomyosarcoma tumor cells have two key differences compared to normal muscle cells: first, unlike developing muscle cells, the tumor cells do not stop dividing and second, unlike muscle cells, the tumor cells do not become specialized to perform contractile function. MET is a cancer-causing gene (oncogene) mutated and misregulated in numerous types of cancers. MET encodes for a receptor protein in a cell called the tyrosine kinase protein, a class of proteins which mediate signals crucial for cellular processes such as survival, movement, division and shape changes. Signaling mediated by MET is required during mammalian muscle development, for the migration of cells that give rise to the muscle,

into target organs such as limbs, and tongue. Recent work from our laboratory identifies SPRY2, a protein which is known to modulate signaling through receptor tyrosine kinases, as a crucial MET regulator. We found that MET and SPRY2 proteins interact with each other in rhabdomyosarcoma cells. This interaction is crucial because loss of SPRY2 function leads to a significant reduction in MET protein levels, indicating that SPRY2 is essential for MET protein stability in rhabdomyosarcoma. This provides a new mechanism by which MET levels are mis-regulated in rhabdomyosarcoma. Notably, loss of SPRY2 or MET resulted in decreased migratory capability in the tumor cells, indicating that these proteins and their interaction is vital to tumor invasive properties. We also find that both MET and SPRY2 are important for rhabdomyosarcoma cell survival and cell division, thus identifying a novel therapeutic intervention point in rhabdomyosarcoma. Reference: SPRY2 is a novel MET regulator that regulates metastatic potential and differentiation in rhabdomyosarcoma. Saini, M., A. Verma, and S.J. Mathew. Cell Death and Disease. February 2018.

Banner image: Flurescent microscopy image of embryonal rhabdomyosarcoma cells labeled for SPRY2 (red), MET (green) and DAPI (blue), showing that SPRY2 co-localizes with MET. Credit: Dr. Sam Mathew

Mechanistic information on the process of cellular waste clearance and novel therapeutics targeting this cellular machinery Dr. Ravi Manjithaya, Intermediate Fellow Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore Recently published research from our lab adds to our understanding of autophagy, the process of cleaning unwanted junk from the cell. Additionally, our research has identified novel drugs that target autophagy pathways and will now be tested in clinically-relevant systems. Every cell in our body is equipped with housekeeping ability. The machinery used by the cell to bring about this is called autophagy. The process of autophagy helps the cell to respond to different

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physical and chemical stimuli by maintaining a constant internal environment. This is brought about by degradation of damaged or surplus proteins or organelles, eliminating invading bacterial pathogens and any dysfunctional protein by autophagy. Accumulation of toxic waste inside cell can lead to cancer, Alzheimer, Parkinson’s and other neurodegenerative disorders. The connection between several disease conditions and autophagy makes the process a target for genetic or pharmacological modulation and of current research interest. Continued on next page…


INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS Normally in a cell, the autophagy process functions at a low level and thus, it becomes very difficult to study it under laboratory conditions. We, therefore, need to externally add or remove certain components required by the cell to induce autophagy to a level of detection. We used nutrient starvation as means to induce it. Our team found that a protein complex called septin, which is involved in cell division or cytokinesis, has a role in autophagy. When cells are deprived of nutrients, it does not undergo cytokinesis. Thus, when cell division does not happen, cell does not use the septin proteins for its division. But to preserve energy it utilizes septin for some other purpose. Our research found that under such conditions, septins help in formation of a structure called autophagosome that collects garbage and thus help autophagy process (1). Further studies about how septins help in the formation of autophagosomes and how they collect the garbage inside the cell would shed light on the autophagy process and its modulation. This knowledge can be used to target autophagy process in a context of a disease.

Additionally, we developed a novel technique to study and screen for molecules that can modulate the process of autophagy (2). This study in a yeast model system provided us with potential drug candidates that we have further characterized in human cells which can now be used in an autophagy-dependent clinicallyrelevant system. Also, with the help of chemical modulators of autophagy, we have identified an autophagy like pathway in a hitherto unknown plant system, Aponogeton madagascariensis. Reference 1. Septins are involved at the early stages of macroautophagy in S. cerevisiae. Barve G, Sridhar S, Aher A, Sahani MH, Chinchwadkar S, Singh S, Lakshmeesha KN, McMurray MA, Manjithaya R. Journal of Cell Science. Jan 2018. 2. Discovery of pan autophagy inhibitors through a high-throughput screen highlights macroautophagy as an evolutionarily conserved process across 3 eukaryotic kingdoms. Piyush Mishra, Adrian N. Dauphinee, Carl Ward, Sovan Sarkar, Arunika H.L.A.N. Gunawardena & Ravi Manjithaya. Autophagy. August 2017.

Controlling intracellular traffic in stem cells can determine its fate Dr. Deepa Subramanyam, Intermediate Fellow National Centre for Cell Science (NCCS) Pune Recently published work from our lab revealed that intracellular trafficking machinery in stem cells can bring about changes in cell fate. Understanding how different cells are formed is a fascinating question. Even more intriguing is the fact that the information to form all these diverse cell types is present in the single-celled zygote, formed by the fertilization of the egg by the sperm. The zygote undergoes a series of divisions over next 3 days, to form a structure called the blastocyst. Cells located within the blastocyst give rise to the entire organism. These cells can also be isolated and maintained in culture, and are called embryonic stem cells (ESCs). Similar to the cells within the embryo, ESCs also possess the capability to generate all the cell types present in the body. So what makes an ESC so special?

It has been shown that the process of vesicular trafficking, endocytosis, which is the transport of molecules using membranebound organelles, can affect the state of a stem cell. We attempted to identify whether specific trafficking pathways were functional in stem cells compared to differentiated cells, and whether this could play a role in maintaining the stemness of ESCs. In other words does an ESC have a specific pattern of expression of genes involved in endocytosis, and does this change when an ESC forms a

specialized cell? In our recently published study, we analyzed the expression of endocytosis associated genes (EAGs) in ESCs versus differentiated cells. Our analysis revealed that the expression of specific EAGs was repressed specifically in ESCs compared to differentiated cells by a novel mechanism involving the action of two modes of repression – transcriptional and post-transciptional. Transcriptional repression involved the action of the Polycomb complex, and posttranscriptional repression involved the action of small non-coding RNAs called microRNAs. Misexpression of these genes in ESCs resulted in a shift out of the stem cell state and towards a differentiated state. Our results suggest that changing the expression of EAGs, and perhaps the functioning of the intracellular trafficking machinery in stem cells, can bring about changes in cell fate. Reference Dual repression of endocytic players by ESCC microRNAs and the Polycomb complex regulates mouse embryonic stem cell pluripotency. Ridim D. Mote, Gaurang Mahajan, Anup Padmanabhan, Ramaraju Ambati and Deepa Subramanyam. Scientific Reports. December 2017.

Novel role for a family of proteins present in the cell wall of a pathogenic yeast that helps it survive in the human host Prof. Rupinder Kaur, Senior Fellow Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad Hospital-acquired invasive fungal infections, a major clinical challenge, are associated with high mortality rates. Candida species are the most common bloodstream fungal pathogens with Candida glabrata being the second most prevalent Candida species after C. albicans. In our research group, we are interested in delineating the factors that help C. glabrata survive in the human host and establish

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infections. In this regard, we have previously shown that C. glabrata is able to survive and multiply in macrophages, which constitute the first line of human defense system. In our recently published work, we uncover a new role for a family of eleven aspartyl proteases, also known as yapsins, that are present at the surface of C. glabrata cells, in suppression of the host innate immune response. Continued on next page…


INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS

Aspartyl proteases are enzymes that cleave peptides and proteins. We show that absence of aspartyl proteases results in activation of the inflammatory response in human macrophages and killing of C. glabrata cells. As cell wall is the first site, that is recognized by host immune cells, this immune activation is likely due to altered structure of the cell wall in the C. glabrata mutant lacking these proteases. Consistent with this, we found aspartyl proteases are required for maintenance of proper cell wall composition and architecture in C. glabrata.

suppresses the host immune response and provides protection against macrophage-mediated killing. Reference: Aspartyl proteases in Candida glabrata are required for suppression of the host innate immune response. Mubashshir Rasheed, Anamika Battu and Rupinder Kaur. Journal of Biological Chemistry. February 2018. Banner image credit (above): Kevin Mackenzie, University of Aberdeen. Wellcome Images. False-coloured scanning electron micrograph of two macrophage cells four hours after infection with Candida yeast spores.

Together, our findings demonstrate aspartyl proteases to be a potent weapon in the anti-host arsenal of C. glabrata which

Molecular markers identified for pseudoexfoliation, a unique eye disease, that helps uncover its association with glaucoma Dr. Aparna Rao, Intermediate Fellow LV Prasad Eye Institute, Patia, Bhubaneswar, Odisha

The focus of my current research is on a unique eye disease, pseudoexfoliation (PXF), which is not only associated with “dandruff like” flaky deposits (see Figure below) in different parts of the eye, but it is also associated with systemic conditions involving the heart, brain liver and other organs. Surprisingly, the exact nature/ source of these deposits, reason for its vast phenotypic/clinical diversity and the mechanism by which this disease leads to glaucoma or blindness in some eyes is poorly understood. Interestingly, the diverse clinical forms of this disease is very well known and understood since 100 years with several earlier studies reporting its frequent association with glaucoma and blindness which is much more than other types of glaucoma.

Contrary to conventional understanding and literature, our recent study published in PLoS One, showed glaucoma with significant changes in IOP with or without optic nerve damage in 30-40% of earlier pigmentary form of the PXF and further found >50% incidence of glaucoma in those with combined phenotypic variants in the same eye. We have identified specific clinical forms of PXF associated with more incidence of glaucoma which mandates closer follow up of these eyes. We are working further to typify each variant and stage with specific molecular signatures in different tissues of the eye before clinically manifest glaucoma which may help identify “at risk cases” and prevent avoidable blindness.

Despite several studies attempting to investigate this entity, it is still unclear which eyes with the deposits would develop raised eye pressure (intraocular pressure, IOP) and glaucoma over time, in the same patient. The proportional risk for developing glaucoma in earlier forms of the disease and various diverse clinical forms of the disease is also not known. Such information would help identify “at risk” features or clinical phenotypes which may signify a risk for developing glaucoma onset even in early disease stages allowing timely intervention and closer follow up.

Reference: Clinical spectrum of pseudoexfoliation syndrome—An electronic records audit. Aparna Rao , Debananda Padhy, Prity Sahay, Amiya Pradhan, Sarada Sarangi, Gopinath Das, Niranjan Raj. PLoS One. 2017 Oct 27.

Figure: Images show differences in clinical pattern of deposits in eyes with pseudoexfoliation which may result in glaucoma in some patients.

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RESEARCH HIGHLIGHTS

by Anusha Krishnan

Prof. Raghu Padinjat

The eye of the fly Is wondrous indeed, For capturing images At uncanny speeds. The molecular signal That makes this possible, Has a biochemical path Believed to be a cycle. Yet mathematics suggests An alternative course, And what appears circular May have a sink and a source! When light falls on the eye of a fly, ripples of messages flow through its cells. These messages are carried by molecular messengers that form an intricate information system that exists not just in the cells of a fly’s eye, but also in most living cells. Since most molecular messengers are not abundant and many are broken down during signal transfer, the cell must renew its stock of messenger molecules quickly and efficiently to maintain its signaling networks. Given this necessity, many molecular messengers are ‘recycled’, where the breakdown products of a signaling reaction are reconstructed via a series of enzymecatalyzed reactions to recreate the original messenger molecule.

Intermediate Fellow National Centre for Biological Sciences (NCBS), Bangalore

Several receptors on the cell surface use PIP2 as an intermediary for information transfer. When such receptors are activated, a signaling cascade is initiated to split PIP2 into two constituents— diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (IP3), both of which further continue the information transfer. Following this, DAG and IP3 were thought to be routed back into a multistep biochemical process to resynthesize PIP2, forming a ‘closed cycle’ with no net loss or addition of molecules during the process. However, when mathematical models using this ‘closed cycle’ assumption were constructed, the researchers found that the models’ predictions failed to mirror experimental data.

However, a new study from the National Centre for Biological Sciences (NCBS), Bangalore, now shows that the regeneration of a membrane-bound messenger molecule, phosphatidylinositol 4,5 bisphosphate (PIP2), is not as straightforward as it was once thought to be.

Under such models, if an enzyme converting DAG into the next intermediate in the PIP2 cycle were to be defective, an increase in DAG levels would be expected. Surprisingly, experimental data from mutant fruit flies with such a defective enzyme showed no increases in DAG levels as predicted.

Mathematical models imply that the commonly accepted ‘closed cycle’ of PIP2 breakdown and reconstruction, with no net addition or loss of molecules to the cycle may not hold true. Instead, it is likely that the PIP2 cycle is an ‘open cycle’, where PIP2 breakdown products are siphoned away to other biochemical pathways, and not fed back into a loop that resynthesizes PIP2.

“It was quite unexpected. We began to realize that perhaps there were gaps in our current understanding of the PIP2 cycle,” says Rohit Suratekar, who worked jointly with the Krishna and Padinjat groups. “After further rigorous investigation, we found that adding two additional reactions at two specific steps in the currently defined cycle could actually explain key experimental data,” he adds.

The work is a collaborative effort between Raghu Padinjat’s and Sandeep Krishna’s groups at NCBS. While Padinjat’s group mainly relies on an experimental approach using fruit flies to understand cellular signaling, Krishna’s group at the Simons Centre for Living Machines in NCBS, takes a theoretical and modeling approach to explore biological phenomena. A result of their combined efforts has led to the discovery that the PIP2 cycle, formulated many decades ago, is not as simple or complete as researchers believed it to be.

Of the two reactions Suratekar mentions, one proposes that the DAG formed as a breakdown product of PIP2 signaling is siphoned away to an undefined biochemical process or a ‘sink’ instead of being funneled into the next step, the formation of phosphatidic acid (PA) for PIP2 resynthesis. The second proposes that the PA required for PIP2 synthesis is acquired from another, as yet unknown biochemical pathway, or a ‘source’. Continued on next page…

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INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS

by Anusha Krishnan

Hence, the traditional ‘closed’ cycle for PIP2 recycling, may now need to be replaced with an ‘open’ cycle where some intermediate products are removed through a ‘sink’ and added through a ‘source’. One reason for this change may lie in the fact that PIP2 resynthesis is spread across two distinct compartments of the cell. Some reactions must occur on the membranes of the endoplasmic reticulum, while others occur on the cell surface membrane. Since PIP2, DAG, and several intermediates of the cycle are membranebound molecules, they cannot diffuse through the water-filled cell interior, and require coordinated transfers between these compartments. “Previous mathematical models of the PIP2 cycle have not taken note of the compartmentalized nature of cells,” says Raghu Padinjat. “Our new models not only account for how biochemical reactions are organized in time, but also include information on how these reactions may be structured in space,” he adds. “The continuous two-way interaction between theory and experiment was crucial for this discovery, and was also incredibly satisfying for us intellectually,” says Sandeep Krishna. “The value of this type of theoretical work lies in clarifying the assumptions that underlie our understanding of biological signaling and regulation, suggests new experiments, which in turn suggest new models, and so on,” he says, adding that this type of approach is crucial for raising entirely novel questions that can be explored experimentally and theoretically. “Relying on models based on the old PIP2 cycle could lead to wrong interpretations of experimental data,” cautions Suratekar. “As

this signaling cascade is involved in many cellular functions, studying this topic is highly important,” he further emphasizes. As Suratekar points out, the PIP2 cycle functions in many cell types. In humans, the cycle is essential for development, proper functioning in immune cells that defend the body against infections and neural tissue that is basis of human brain function. Genetic defects in elements needed to run the PIP2 cycle have been linked to various cancers, neurological diseases, and mental illness. “Designing drugs/inhibitors to treat human disease is often aided by a thorough insight into the biochemistry underlying the function of cells and tissues. Thus, a clear understanding of the organization of the PIP2 cycle may be crucial in designing drugs for therapy,” says Padinjat, adding that in the future, his group hopes to refine their new mathematical model to predict the effects of therapeutic drugs which act via the PIP2 cycle to modify cellular functions. Mukund Thattai, a faculty member from the Simons Centre unconnected with the study comments, “this project really reveals how theory-experiment collaborations work. It is a process, a backand-forth conversation; it takes time for each side to become comfortable with the other. Theorists start with the least amount of detail necessary, and experimentalists are confronted with all the detail at once. What's really commendable is how Rohit has managed to strike the perfect balance." Reference Evidence of sinks and sources in the phospholipase C-activated PIP2 cycle. Rohit Suratekar, Aniruddha Panda, Padinjat Raghu, Sandeep Krishna. FEBS Letters. February 2018

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INDIA ALLIANCE

FELLOW IN SPOTLIGHT

Dr. Sucharita Sambashivaiah Intermediate Fellow St John’s Medical College, Bangalore

Please tell us what you are working on and what impact do you hope it will have?

Is there a research area other than yours that interests you deeply?

The growing burden of Type 2 Diabetes Mellitus in India is of concern. The primary targets of insulin action to maintain glucose homeostasis are the skeletal muscle, liver, and adipose tissue. Among these, skeletal muscle is considered to be the largest insulin-sensitive organ. Despite normal body mass index, many Indians may be at risk of becoming insulin resistant, raising the possibility, that insulin resistance is related more to regional rather than general adiposity. Fat storage in non-adipose tissue could exist independent of generalized adiposity making it difficult to establish true associations between insulin resistance and body mass index. The present standard recommendations to either prevent or treat Type 2 Diabetes, are modifications in lifestyle habits. With a preexisting low muscle mass, it will be very important to evaluate the impact of caloric restriction, protein supplementation and resistance exercise in regulating and maintaining insulin sensitivity in Indian population. We are working towards understanding the role of skeletal muscle in the aetiology of Type 2 Diabetes in the Indian population and to evaluate the efficacy of interventions designed to target improvements in muscle mass, function and metabolic potential. A better understanding of the cause(s) of the predisposition of Indians to become Type 2 Diabetes will be very useful in evolving healthcare policy. Can you share some interesting findings from your research on "thin-fat Indians"? Asian Indians are thought to have a greater propensity for a phenotype that is characterized by an excessive accumulation of fat for a normal body mass index (BMI) (kg/m2), which has been termed ‘metabolically obese’, or simply ‘thin-fat’. They have also been demonstrated to be at a greater risk of becoming profoundly insulin resistant, even with a normal BMI, suggesting that their insulin resistance is related more to regional (muscle) rather than general adiposity. There is little information about intramyocellular fat (IMF) among Indians with prediabetes. As part of the cross-sectional component of my studies, quantitative histological examinations of biopsied quadriceps muscle cells from individuals with prediabetes and their age-matched controls were performed. These groups of individuals were comparable in terms of their BMI, muscle to fat ratio and beta cell function. Oil red O staining performed on biopsied tissue sections to identify their lipid content demonstrated a higher lipid accumulation in prediabetes group, such that the proportion of total area occupied by IMF was thrice than seen in controls. In comparison with Western populations with Type 2 diabetes, the skeletal muscle IMF content of Indians with prediabetes was 3 times higher. The current analysis provides proof of the existence of ectopic fat (IMF) among Indians with prediabetes. Further my fellowship will be able to evaluate the mechanisms that lead to the deposition of IMF and how reversible this phenomenon could be with lifestyle intervention programs such as exercise and diet.

Apart from working in the field of chronic diseases especially Type 2 Diabetes, I have always been intrigued with the process of ageing. There is always a difference in biological ageing versus chronological ageing. To lead a healthy and longer life it is important to focus on biological ageing. Evaluating factors modulating ageing and improving quality of life of an elderly through interventions interests me. In addition, being associated with skeletal muscle research of late, I have developed interest in understanding mechanisms underlying biomechanics especially in an athlete. How has Wellcome Trust/DBT India Alliance funding helped you and your research? The structure of fellowship program, flexibility in funding and platform provided for the fellows to setup and execute ideas is a blessing. The Wellcome Trust/DBT India Alliance fellowship gave me confidence and liberty to achieve things which otherwise would have been difficult. The Intermediate Fellowship gave me a platform to setup independent lab, explore, collaborate and translate research. The lifestyle modification program customized as part of the fellowship is now being accepted by the front end clinicians after seeing the benefits to the patients. The skeletal muscle function lab has gained momentum by itself, with clinicians wanting to evaluate skeletal muscle functional assessment for various clinical conditions. This fellowship allowed me to achieve my dreams of having an independent setup, test ideas and adapt it to see transformations.

Above: Sucharita’s muscle function lab Below: Study participant undergoing gym training as part of the lifestyle modification program

Continued on next page…

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INDIA ALLIANCE FELLOW IN SPOTLIGHT

Dr. Sucharita Sambashivaiah

How was your transition from being a clinician to a public health researcher? Any specific challenges you faced as a woman researcher?

department motivates me to reach newer heights.

I have been heading a Clinical Service Unit since couple of years now. The fact that I have been able to provide diagnosis and help in the treatment aspect has always sustained me to run the unit, in spite of challenges which accompanies it. The field of public health research has given me platform to help people at a larger scale. The transition for me has been really enjoyable and would recommend clinicians go through the same. The Wellcome Trust/DBT Indian Alliance fellowship offers clinicians to work closely with human disease-related questions. I believe if more and more clinicians could be part of such programs, future of Indian clinical research will be bright. Being a woman researcher I have not specifically faced any challenges. There are challenges which each and every researcher goes through, it is the way one looks at it and overcomes with positive attitude that matters. Any advise (from your own personal experience) for clinicians hoping to make the same transition? As a teacher to medical students, I feel it is high time we start sensitizing our medical graduates about the process and benefits of doing medical research. It should start early to have a greater impact later. In addition, the advantage of being a clinician one will be in a first-hand position to ask clinically-relevant research questions. Based on my experience one could translate some component of the research questions effectively. I would highly recommend young clinicians to utilize opportunity provided by fellowships offered by the India Alliance. What keeps you going everyday? Being able to face challenges every day and overcome it keeps me going. The hope and belief that the clinical research will soon help patients keeps me motivated. The ability to fill hope and aspiration among young researchers and clinicians makes me work harder. Last but not least is the highly inspiring work environment in my

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Sucharita and her team regularly conducts medical camps to increase awareness of Pre-diabetes as part of the public engagement aspect of the fellowship


INDIA ALLIANCE

WORKSHOPS

Developing Indian Physician Scientists (DIPS) workshop 4-7 March 2018, Hyderabad The second Developing Indian Physician Scientists (DIPS) workshop, was held at Centre for Cellular and Molecular Biology, Hyderabad from 4-7 March 2018. The workshop held over four days, introduced 33 young clinicians from around the country, to quantitative methods and research methodology and provided them an opportunity to discuss the relevance of biomedical research and career options with eminent Indian physician-scientists. Workshop faculty consisted of Dr. Anurag Agrawal, Dr. Rakesh Aggarwal, Dr. Giriraj Chandak, Dr. Rakesh Mishra, Dr. Sundeep Salvi, Dr. Amitabh Chattopadhyay, Dr. Vinod Scaria, Dr. Koundinya Desiraju, Dr.

Debojyoti Chakraborty, Dr. Sridhar Sivasubbu, Dr. Dipyaman Ganguly Dr. U Mabalirajan, Dr. Thangaraj and Dr. Manikandan Subramanian. The Developing Indian Physician Scientists (DIPS) workshops have been designed by Dr. Rakesh Aggarwal (SGPGI, Lucknow) and Dr. Anurag Agrawal (CSIR-IGIB, New Delhi) and facilitated and supported by the Wellcome Trust/DBT India Alliance. For more information on these workshops, visit http://www.wellcomedbt.org/news/164

Science Communication workshops India Alliance regularly organizes one-day Science Communication workshops across the country to train PhD students, Postdoc scholars and Clinical researchers in written and oral communication skills and provides guidance on making the right career choices. One-day SciComm101 workshop was held at Bhabha Atomic Research Centre (BARC), Mumbai, on 3 February, which was attended by around 80 PhD students, research staff and junior faculty from various departments. On 28 February, India Alliance in partnership with Nature India organized its one-day Science Communication and Career Workshop at Bio-Gene-Sys2018, national meeting organized by Pondicherry University. This workshop equipped young science

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researchers with tools and strategies for effective communication of their ideas, experiments and scientific results from a science communication perspective and discussed science career opportunities with the participants who came from various institutions from around the country. India Alliance also organized one-day SciComm101 workshop at Ahmedabad University on 9 March. To request a one-day Science Communication workshop at your institution or at a conference you are organizing, please visit our website for more details and send your request to workshops@wellcomedbt.org


INDIA ALLIANCE

EVENTS Life outside the lab: insights from researchers who chose to shed their lab coats Careers in Science 1 February 2018, Hyderabad

By Divya Raghuram

This article was first published on IndiaBioscience.org

As someone who has just entered the world of postdoctoral research, I registered for the “careers in science” workshop organised on the heels of ICCB 2018 at CCMB, Hyderabad, with a lot of curiosity. In hindsight, I am quite glad I attended the workshop, as it presented a fantastic opportunity to learn about the various careers open to science graduates, from the very people who have explored these options and are now established in their own niche areas. The workshop was organised by IndiaBioscience and Wellcome Trust/DBT India Alliance. Shahid Jameel of India Alliance started the session with a short introductory talk, where, he emphasised on the need to look beyond academic careers in science. First speaker of the day, Smita Jain, Associate Director at IndiaBioscience, talked about various career-related eresources available on the IndiaBioscience website. Ever since, I have been a regular to their website which holds a good repertoire of fascinating videos and a very informative booklet on careers in science. The Young Investigator Meetings(YIMs) she mentioned, would be extremely useful to young postdocs for networking with senior faculty members from institutes across the country, mentorship and community building. Jain also spoke about careers in science administration and management. She stressed on the need to “introspect before making a career choice” and eventually choosing something that resonates with your personality. The second talk of the day was delivered by Suveera Dhup, Grants Manager at India Alliance. Dhup took us through her personal journey, that started as a PhD student at National Institute of Immunology followed by a postdoctoral stint abroad and finally a chance encounter with somebody gave her the idea to apply as a Grants adviser at DBT-India Alliance. She also elaborated on the skills required in a grants manager and gave the audience a lowdown on what she loves and hates about her job. Coming from someone who has made a career shift from bench to an allied science field, this talk was definitely a great inspiration for people in the audience who were thinking of changing tracks from core academia. I was personally quite enthralled with Chitra Ravi’s talk- the third speaker of the day, who is also a faculty at Azim Premji University. After a very long time, I saw a person who did not use any presentation aids and yet could hold her audience in rapt attention for around 25 minutes. She talked about educating science teachers to help improve their pedagogy. This is something I had never thought about before and found to be quite interesting. She also talked about her experience as the co-editor of iWonder, a magazine for middle school teachers. Her work involves interaction with teachers to help them integrate experiential learning into

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their classrooms. Subhra Priyadarshini, Editor of Nature India, spoke about science journalism as a career option. She elaborated on medical and technical writing in media houses, publications and companies that recruit science writers. It was quite reassuring to know that a huge platform like Nature India actively encourages PhD graduates and postdoctoral fellows to contribute write-ups or do internships to get a hands-on experience in science journalism, before making the crucial career jump. She ended her talk with a short audio from Nature India podcast on the pioneer of DNA fingerprinting, Dr.Lalji Singh. Podcasts, still at a nascent stage in India, as she pointed out, are again a great opportunity for outgoing researchers to tap in and carve a niche for themselves. Arun Chandru’s talk gave a great insight into what it takes to start and run a startup. After a doctorate in aerospace engineering, he changed tracks to co-found Pandorum Technologies, a life sciencebased startup, working on designing artificial human tissue. He spoke about the challenges he faced in securing funding for their start-up, their vision of developing complete organs for medical research and therapeutic applications and gave a brief about the incubator, Centre for Cellular and Molecular Platforms (C-CAMP), where Pandorum Technologies is located. Chandru also said that a lot of government grants and other forms of financial support is now becoming available for deep-science driven startups, all you need to do is to “attract it”. Lastly, a career talk by Shyam Suryanarayan, from SciTal, addressed the issue of employability and career readiness that students ranging from bachelors to PhD face when looking for opportunities outside academia. A basic personality type check, such as the MyersBriggs Type Indicator® (MBTI®) could be a good starting point for those who are not sure which jobs they could fit in. He also summarised a range of job opportunities according to personality type, which I could immediately put to use in my own ongoing job search. The tea and lunch sessions provided a great opportunity to meet and interact with the speakers for one-on-one discussions about specific queries. The enthusiasm and the genuine interest of all the speakers to help students in any way they could, was definitely palpable in the environment. More such career workshops in various institutes will be a great guidance and exposure to life science students.


INDIA ALLIANCE EVENT REPORT

India Alliance – Science Policy Session on Global Challenges: Policies for funding research at International Congress of Cell Biology (ICCB) 2018, Hyderabad India Alliance organized Science policy session at the International Congress of Cell Biology in Hyderabad on 31 January 2018. This event, moderated by the India Alliance CEO, Dr. Shahid Jameel, brought together prominent researchers from India and overseas to address the opportunities and challenges for Life Sciences research in India, and to discuss the way forward.

ecosystems and how they can better connect, communicate and engage with the public, industry, policymakers, and science funders. India currently spends 0.7% of its GDP on scientific research. The speakers emphasised that increase in GDP spend on research is much needed but adequate infrastructure must be in place to absorb this rise. It was discussed that there exists a need for both basic and translational research in every country, irrespective of their socioeconomic status. It was also observed by some experts in the panel that presently researchers in India need handholding to translate their discoveries into products. And it is, therefore, imperative for scientific institutions to connect with the industry. While it was suggested that the Indian government stays the primary funder of science in the country, gradually as the private funds in science increase regulations have to be also carefully drafted and implemented so as to not compromise the rigour or intellectual property rights of the researchers. Panelists also agreed that good research management practices and open data are the tools that the scientific community will find handy in accelerating their research as well as to have a better connect with the international research community and the society at large. The panel unanimously underlined the importance of a collaborative culture at any Indian scientific institute to help in its progress. The necessity of connecting undergraduate students with the research community was also stressed by all the panellists to develop better scientific competence in the country.

Dr. Shahid Jameel setting the stage for the discussion. Photo credit: CCMB, Hyderabad

The panel comprised of Drs. Dr Vineeta Bal (IISER, Pune, India) Prof L S Shashidhara (IISER, Pune, India), Prof Michael Ferguson (University of Dundee, UK) Dr Bernd Pulverer (EMBO, Germany) and Prof William Earnshaw (University of Edinburgh, UK). The session focused on how India can build high quality research

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The learnings from the session is believed to help provide the essential points of deliberation for research institutes as well as funders towards framing the future of science and research in India. YouTube link of the session. With inputs from Somdatta Karak


INDIA ALLIANCE

PUBLIC ENGAGEMENT

Event report

Actor- Doctor Staging Public Health Matters The Project; Actors and Doctors: Staging Public Health matters was an endeavour by the Darpana Academy of Performing Arts , Ahmedabad, to initiate a two-way learning process between distinct yet connected fields of social and scientific enquiry. This we hope would lead to a more informed artistic and scientific practice and also result in initiating public discourse on important health issues. The two pronged approach of this art and health engagement aimed to, sensitize artists and art organisations to use public health as a theme for conceptualising and creating theatre and performance-oriented entertainment pieces for the general public. Additionally, the project aimed to address the growing debate within the research fraternity of making research more accessible to the public i.e. to actively involve the public in public health research. This part of the project involved exposing the public health researchers to innovative ways of reaching out to the public which would help bring out the “human” element of Public Health research. This project received funding support from the Wellcome Trust/DBT India Alliance. The implementation of India's first Public Health Theatre Festival, “Actor Doctor Project” started off with a two-day sensitization workshop held on the 16th and 17th December 2017 at Darpana Academy of Performing Arts, Ahmedabad and the final showcase on 17 February 2018.

The workshop’s purpose was to sensitize the participating theatre groups ; doctor experts collaborating on the project as well as expert performing artists to meet under one roof. Hear , learn , discuss and share their view points through words and imagery one topic that is public health. The two-day workshop interaction focused on three aspects providing understanding on a) public health issues, health communication methods & research; b) how theatre has been and can be used as a tool and most importantly c) the sensitivity in the portrayal of health issues on stage. Following this workshop, the Public Health Theatre Festival was organized on 17 February where the doctors and actors set up shows in various locations in Ahmedabad. The Actor Doctor Project lead video documented twenty performances across the city of Ahmedabad. Developed by young actors and directors in close conjunction with specialist doctors, the five different performances covered the fields of sex education, mental health and depression, environmental health and the need for balanced nutrition. This is the first time that such an expansive research project has been undertaken with expert doctors working in close conjunction with people from the creative world, to education ate the public. Performances took place in City and BD colleges, Anjuman Islam and MGIS school, Vanita Vishram, in the displaced peoples’ colony of Ganesh Nagar next to Piranha, around the University area, in two poles and at Law Garden, for very varied audiences. Feedback was sought from audience members and this will be analysed to determine the efficacy of using theatre to communicate public health messages. The aim of this project was to explore a unique way to deal with India’s health crises by using edutainment to empower people, to take knowledgeable decisions for preventive care. Details of the learnings from this project will be published soon so that this format can be scaled up. Click here to find out more about this project. Dr Kartik Sharma Project Lead, Actor-Doctors: Staging Public Health Matters Darpana Academy of Performing Arts, Ahmedabad

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INDIA ALLIANCE

PUBLIC ENGAGEMENT

Release of “Women in Science – A Listening Session” Report on International Women’s Day 8 March 2018 To better understand the landscape facing women in science in academia in India, the Wellcome Trust/DBT India Alliance (India Alliance) and the U.S. Embassy had organised “Women in ScienceA Listening Session” on 16 November 2017 at ICGEB, New Delhi, in which both policy makers and women in academia came together to engage in constructive dialogue about opportunities for supporting the advancement of women in science nationally and internationally. Dr. Ellen Carpenter, program director at the National Science Foundation, in the Division of Undergraduate Education and U.S. Embassy Science Fellow moderated the session. A detailed report and recommendations from this meeting can be downloaded here.

L-R: Hon’ble Dr. Harsh Vardhan, Dr. Anil Kakodkar, Dr. Ashutosh Sharma, Dr. Paramjit Khurana, Dr. Shahid Jameel

The Report was introduced by Dr. Shahid Jameel, CEO, India Alliance and released by the Hon'ble Union Minister for Science & Technology & Earth Sciences, Dr. Harsh Vardhan, at the "National Conference on Technological Empowerment of Women, organised by National Academy of Sciences, India (NASI), on 8 March 2018 to commemorate the International Women’s Day. Also present at the release were, Dr. Anil Kakodkar (President, NASI), Dr. (Mrs.) Manju Sharma(Distinguished Women Scientist Chair, NASI), Prof. Ashutosh Sharma (Secretary, Department of Science & Technology, Government of India), Prof. M. S. Swaminathan (Chairman, Advisory Committee, NASI Conference), Prof. Paramjit Khurana (General Secretary (OS), NASI) and Dr. Karen Nelson (President, J. Craig Venter Institute, USA).

Dr. Shahid Jameel at the NASI event

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INDIA ALLIANCE PUBLIC ENGAGEMENT

Women in Science series The Life of Science The India Alliance is supporting the project The Life of Science’ s “Women in Science series” that aims to highlight the work and challenges faced by women scientists in India and to showcase these scientists as role models for young girls. The Life of Science is a science media platform currently focussed on women scientists in India. Through this series, TLoS will feature around 30 India Alliance women Fellows through writing pieces, photo features, podcasts, etc. on their website and other popular media

Photoessay: Krishnaveni’s life-long medical case studies

channels over the next few weeks. Below are some of the India Alliance Fellows covered in this series so far. Click on the photo or the text link to read their stories. TLoS is currently working on two books on Indian Women in Science. You can support their endeavor here.

Sonam’s toolbox for DNA repairs

Mahak Polices Traffic in Cell City

On the tiger trail with Uma

Suhita’s No Garland Neuroscience

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INDIA ALLIANCE

NEW INTIATIVES

The Africa-India Mobility Fund (AIMF) is a two-year programme designed to provide researchers from Africa and India with opportunities for short visits in either direction to explore opportunities for building and strengthening scientific collaboration.

more people lead healthier lives. One of the ways individuals grow as leaders is through mobility, collaboration and broadening of experience.”

The AIMF initiative by the Wellcome Trust/DBT India Alliance (India Alliance) and the African Academy of Sciences intends to encourage South-South collaborations and learning between the two ecosystems. This is in recognition of the fact that Africa and India face similar challenges, both in the diseases that affect their populations and socio-political issues as well as the leadership required to address these. The exchanges are expected to enhance their skills and contribute to the growth of knowledge and leadership towards common health challenges.

Purpose To establish links and cultivate a culture of collaboration between African and Indian researchers that will serve as a vehicle to improve research capacity and build leadership in biomedical and clinical research for Africa and India.

Purpose, Objectives and Scope of the Initiative

In Africa, the travel grants will be administered by the Alliance for Accelerating Excellence in Science in Africa (AESA) and in India by the India Alliance.

Objectives To strengthen research & innovation capacity and knowledge exchange To strengthen scientific collaboration between Indian and African teams Scope

“We are pleased to be launching these two schemes, which provide an opportunity for researchers to build strategic partnerships to harness science to transform lives of Africans and Indians. Shared challenges between African and India, including a high disease burden for both communicable and non-communicable diseases, require a multi- and interdisciplinary research approach to problem solving and knowledge creation,” said AESA Director Prof Tom Kariuki. “Africa and India share many problems of health and the asset of a young population. India Alliance is pleased to join hands with AESA and AAS in launching this Africa-India Mobility Fund. We hope that the coming together of researchers from these geographies would lead to sustainable solutions for our common problems”.Dr. Shahid Jameel, CEO, Wellcome Trust/DBT India Alliance. The AIMF comes on the heels of the Third India-Africa Forum Summit held in October 2015 and where Heads of State adopted the Delhi Declaration renewing their commitment to work with each other, and outlining the priority areas and ways in which Africa and India can work together to improve the lives of their people. It is also one of many efforts to exploit the synergistic relationship between Africa and India outlined in the India Africa Health Sciences Summit held in 2016. Over the last two years, the India Alliance and AESA have also hosted African and Indian biomedical researchers, respectively, at their Annual Grantees Meetings. These travel grants will be supported by the India Alliance (for Indian researchers) and the Wellcome (for African researchers, administered through AAS and AESA). Dr Simon Kay, Wellcome’s Head of International Operations and Partnerships, said “At Wellcome we are passionate about supporting researchers in Africa and India to become leaders in biomedical and health research, inspiring and training the next generation and helping

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Applications broadly focused on infectious and non-communicable diseases of relevance to local, national, or global health will be accepted every month. The scope of the collaborative opportunity may include but is not limited to HIV/AIDS, TB, dengue, malaria, vector-borne diseases, parasitic infections, emerging infections, cancer, diabetes, hypertension, health systems research, antimicrobial resistance, drug development, microbiome and general biomedical sciences. While applications that involve existing collaborations will be considered, applications that target new collaborations and encourage diversity especially female and young applicants are particularly encouraged. Application Process, Review and Deadlines Applications for the Africa India Mobility Fund open on 3 April 2018. All application forms should be submitted through the AAS Grants Management System (Ishango). Register as a user to apply. See sample application form here Click here to find out more about these travel grants. References: Why it’s time African researchers stopped working in silos. The Conversation. May 2016 Health research: Africa–India health-science partnerships. Nature. September 2016 Outwards to Africa. The Hindu, September 2016 Bringing together African and Indian Biomedical Researchers. India Alliance Newsletter, September 2016 India meets Africa again: Recognising common research goals and mapping the road ahead. India Alliance Newsletter, September 2017


INDIA ALLIANCE NEW INTIATIVES

IRMI: an initiative to strengthen institutional ecosystems The new initiative of Wellcome Trust/DBT India Alliance, India Research Management Initiative (IRMI), will provide a mechanism for enabling research management at institutions in India thereby help them to navigate the high demands for funding, outreach and governance of research. In this interview originally published by BioVoice, Dr. Shahid Jameel, CEO, India Alliance and Dr. Savita Ayyar, Consultant IRMI share more details of this initiative. participating in the IRMI initiative will have the opportunity to discuss this and future requirements with the IRMI team. Research management requires professionals who are able to span diverse skills including science. As the IRMI program evolves, it is expected that there will be opportunities created for non-academic careers in science, at multiple institutions across the country. The IRMI program will help with creating standards for research management roles at participating institutions. In the longer term, IRMI would enable Indian institutions to have successful research managers in place and for these individuals to be connected through a professional national network. Such a network will be hugely enabling for their career growth and professional competence. Individual excellence will feed back into the research institutions.

What was the thought process behind the launch of IRMI? Any experiences in India that were discussed during the initial stage, leading to brainstorming and ultimately finalization? Research is an international activity driven by curiosity, social need and technology. Research across the world is influenced by developments such as international opportunities for collaboration, funder priorities, emerging technologies and the cost of research infrastructure. This landscape has led to the creation of a new support system for research worldwide, which is at the boundaries of science and society and is termed as Research Management. In today’s world, every research organization requires access to a well-developed research management base in order to continue being internationally competitive. India is making significant strides in science and technology. There is a lot that is expected of Indian researchers, both in terms of contribution to knowledge generation worldwide and in generating research-based solutions to India’s unique problems. IRMI arose in response to the need for reducing the amount of time spent by Indian researchers on administration, for generating a cadre of professionals able to support research management in India and to allow Indian researchers to make the best use of international collaborative funding opportunities. There is now awareness about the need for Research Management, as brought out at workshops and sessions steered by organizations including the Wellcome Trust/DBT India Alliance. However, a recent scoping exercise commissioned by the Wellcome Trust, UK and implemented across a section of Indian institutions by the Wellcome DBT/India Alliance, suggests that Research Management is not widely practised at Indian research institutions. The IRMI pilot will help to establish a more detailed account of research management prevalence at Indian research institutions, to identify gaps in the system and to create solutions addressing these gaps in the longer term. What should the research institutes expect from this initiative? The IRMI pilot phase is expected to create awareness about research management in India, in a dialogue facilitated by the India Alliance with research institutions. A key aspect of this is to help institutions share their learning, identify gaps and find longer term solutions, towards a goal of streamlined research management. Each research institution has a specific scientific mandate, which will govern the details of its research management needs. Institutions

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Please explain to us the methodology that would be followed once an institute decides to join in? How would be the progress measured? Institutions wishing to participate in IRMI should complete a registration form available on the India Alliance website. Participating institutions would have the opportunity to discuss their research management systems and future requirements with the IRMI team. There will be training and networking opportunities made available through IRMI, both for entry level research managers and for more experienced ones, who require support for career progression. Details for these opportunities would be shared on the India Alliance website as appropriate.

A small number of institutions will receive detailed support for setting their research management support in place. This decision will be taken by the India Alliance based on learning opportunities and institutional commitment. Success of research management at participating institutions will be assessed in the longer term. What is the deadline for participating in the initiative? How have the various institutes in India responded to it so far? There is no deadline, this is an open call. There have been several expressions of interest from research institutions carrying out both basic and translational research. These include institutions with existing research management infrastructure who are looking for career development opportunities and also institutions wishing to make a start.

What is the total budget for this initiative? Would it be an annual exercise now and what are the long-term goals? The IRMI pilot will be implemented over 2018. Outcomes from this phase will determine its future directions and scale. What kind of challenges do you expect during implementation? Any new initiative always encounters challenges. A key aspect of the IRMI pilot will be to identify the gaps in research management across diverse organizations in India. The success of any such programme would depend upon the full participation and commitment of institutions and a willingness to adapt and change for the better.

Interested institutions can register their interest in participating in IRMI pilot here


INDIA ALLIANCE

STAFF CORNER

Dr. Shingar Sharma Grants Adviser, India Alliance

What is your background?

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

My family hails from Punjab and Haryana. I was born in Lucknow, after which my parents moved to the USA for some time, where my father did his postdoctoral work at the Scripps Research Institute. We then moved back to Delhi, where I have lived all these years. I completed my entire education, from primary school to PhD, in this city. I have spent several memorable years at the Delhi University where I joined as an undergraduate student in Zoology (Gargi College) and then went on to do my PhD at the Department of Biochemistry, South Campus.

I don’t have much leisure time these days but I cherish the desire to learn playing the guitar someday.

What led you to a career in research/grants management?

It was during the second year of my PhD that a casual conversation with one my professors sparked my curiosity about non-academic careers for science graduates. The words that stuck in my mind from that conversation were “public health projects, WHO, UN, funding”. This got me thinking. I talked with older friends and senior colleagues, who gave useful advice and listed out all the good, the bad and the ugly about academic and non-academic career choices for PhDs. I became highly fascinated with the alternative choices. My father himself offered valuable advice and support, even though I was hesitant initially to tell him that I did not want to go for a postdoc. It was on his encouragement that I finally started applying for positions in funding agencies and as luck would have it, landed my first job at DST! At the Technology Development Board, we funded commercial entities for developing and implementing innovative technologies and scientific solutions across the entire spectrum of economic sectors that the Government of India supports. I mainly handled the medical devices sector portfolio. How has your India Alliance journey been so far and what are you looking forward to?

I joined the India Alliance in July 2017 and it has been a wonderful learning experience. I thoroughly enjoy being part of a very capable and talented team, where I have learnt the importance of camaraderie. I am glad to be part of the process that supports and enables brilliant minds of the country to carry out scientific research par excellence, and further helps to shape a thriving research ecosystem. It is indeed a great platform for me to get to know about the cutting edge research being done, even though I am no longer an active researcher. I have attended the Science Communication workshops, and other conferences and symposia supported by the India Alliance and have enjoyed every moment of it. I am eagerly looking forward to the times to come and playing an integral part in the workings of this organization.

22.

Which book are you reading right now? I recently finished reading The Last Man by Mary Shelley, which is a fiction novel describing a post- apocalyptic world where humankind is being wiped out by a plague pandemic. It is a very enjoyable read, despite the dark themes, or maybe I just prefer dark stories. The protagonists of the story are in fact based on Percy Bysshe Shelley and Lord Byron. (I have always harbored a strange adoration for Byron “mad, bad and dangerous to know”) What was the last piece of research that you found exciting? Stephen Hawking’s recent passing away generated a lot interest and buzz about the last paper he was working on. I read some articles on it, though the actual paper itself (pre-print version) is beyond my understanding since it is all theoretical physics. However, I was quite fascinated by the thoughts put forth in that paper that perhaps we can find evidence in background radiation of our universe being just one of many in a multitude of universes (“multiverse”) arising from the phenomenon of eternal inflation (space-time expansion, the kind that happened after the Big Bang). Who inspires you (living or dead)? My biggest inspiration, aside from my parents, is Dr. Daisaku Ikeda, a Buddhist scholar, philosopher and peace activist. He is the president of the Soka Gakkai (society for value-creation), a worldwide community-based organization dedicated to promoting peace, culture and education based on the humanistic principles of Buddhism. He is a champion for the cause of nuclear disarmament, an author, a poet, a photographer. Dr Ikeda has conducted dialogues with world leaders in the fields of politics, academics, culture and education, with the firm belief that only open and honest dialogue can be the foundation of lasting peace. This begins with the selftransformation of an individual (a concept termed “human revolution”), the ripples of which spread out into the immediate community and further in society thus creating a network of empowered global citizens. His life is an incredibly inspiring journey, overcoming seemingly insurmountable odds through sheer determination and perseverance. And it inspires me to cultivate a vision that goes beyond just my own small world to a much vaster horizon and work towards not just my own happiness but for others as well.


OTHER ANNOUNCEMENTS

1)

NEXUS Startup Hub

diagnostics and devices that meet certain criteria.

On February 8, 2018 the U.S. Ambassador to India, Kenneth I. Juster, launched Nexus - an innovation hub and a business incubator housed at the American Center, New Delhi. TheNexus Incubator, through its flagship “Pre-incubation program” offers selected startups excellent access to a networks of industry and government partners; training from the top commercialization experts around the world; an extensive mentor network as well as access to both private, and public fund managers specializing in supporting startups. Aspiring Women Entrepreneurs offers free training and a trip to The University of Texas at Austin to help young women take innovations to market. Eligibility: women who are currently enrolled in an Indian university and who have a specific innovation to commercialize may apply by March 16.

2) CARB-X – Call for applications

Combating Antibiotic-Resistant Bacteria Accelerator (CARB-X), a U.S. Department of Health and Human Services (HHS) initiative, announced its 2018 rounds of funding to support research into the development of antibiotics, vaccines, diagnostics, devices and other life-saving products to respond to the threat of drug-resistant bacteria. 2018 Funding Round 1 will open for Expressions of Interest on March 22 through March 29, 2018, with the scope restricted to new classes of direct-acting small molecule and large molecule antibacterials that target certain Gram-negative bacteria. • 2018 Funding Round 2 will follow, with Expressions of Interest welcome starting on June 1 through June 8, 2018. Round 2 funding includes direct-acting therapeutics and covers a broader scope of therapeutics, vaccines, •

Full details of the scope of both funding rounds can be found here.

Information about the application process can be found here.

3) 2019 Fulbright Fellowship- Call for applications The United States-India Educational Foundation (USIEF) announces the opening of its annual competition for Fulbright-Nehru, Fulbright-Kalam and other Fulbright fellowships. Such exchanges have helped bring the people of India and the United States closer together through opportunities that enrich fellows’ academic, research, teaching and professional capacity. USIEF expects to offer approximately 100 Fulbright-Nehru and six Fulbright-Kalam Climate Fellowships to Indian applicants in 2019. Fellowship details are posted on the USIEF website (www.usief.org.in) and the first application deadline is June 15, 2018. Applicants may send any queries to ip@usief.org.in or contact one of the USIEF offices in New Delhi, Chennai, Hyderabad, Kolkata, or Mumbai.

4) Hamied Foundation UK-India AMR Visiting Professorships These awards support short visits that seek to facilitate collaboration between the most talented researchers in the field of antimicrobial resistance (AMR) in the UK and India. Key dates The first round is now open. Deadline: Friday 06 April 2018, 16.00 GMT.

Please send your feedback, suggestions and contributions to public.engagement@wellcomedbt.org Follow us on www.wellcomedbt.org 23.


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