India Alliance Newsletter I Issue 19 I January 2018

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News & Views Issue 19 January 2018


EDITORIAL Best wishes for the New Year from all of us at the India Alliance. In the first issue of 2018 we bring to you updates on our Fellowships and events, new research stories by India Alliance Fellows, new initiatives and interviews. We hope you find this issue an engaging and informative read.

To begin with, heartiest congratulations to our Senior Fellow, Dr. Vikram Mathews (CMC Vellore) for receiving the Sun Pharma Award for Medical Sciences, Indo American Cancer Associations’ Lifetime Achievement Award for Outstanding Contributions to HematologyOncology and for being elected to the Indian Academy of Sciences (Bangalore). We are also happy to share that Dr. Arun Shukla (IIT Kanpur), second IA Fellow (and scientist from India) has been selected as EMBO Young Investigator. Congratulations to him! Updates on the Fellowship front- we are presently accepting applications for our Senior and Intermediate Fellowships (SIF) and Clinical and Public Health Research Fellowships (CPH). Check our website for regular updates on our funding schemes. This issue also includes recently recommended India Alliance Fellowship awardees. As always, we are pleased to bring to you a diverse mix of recently published research of our Fellows in the Research Highlights section. Dr. Subba Reddy Maddika and his team at CDFD Hyderabad have found a new role of a tumour suppressor protein in regulating glucose uptake by cells. Dr. Roop Mallik and Dr. Priyanka Rai’s (TIFR Mumbai) recently published research in collaboration with IA Fellow Dr. Siddhesh S. Kamath (IISER Pune) provides new insights into the regulation of fat secretion from the liver and Hepatitis-C virus replication. This work suggests possible drug targeting of this chronic virus by blocking an important transport mechanism of fat droplets inside liver.

Some of these research stories were also covered in the popular media, links of which are included in this section. This issue also includes interview of our Intermediate Fellow Dr. Smarajit Polley at Bose Institute and profiles of our new Fellows. This issue also features an article by Intermediate Fellow at ACTREC Mumbai, Dr. Sonam Mehrotra, in which she writes about how she got her research career back on track after a two-year break from work with a DBT and then an India Alliance Fellowship (part of Journey of Investigator JOYI series by IndiaBioscience). The first Developing Indian Physician Scientist (DIPS) workshop was held from 23-26 November at CSIR-IGIB, New Delhi, a short report of this workshop is included in this issue. Next DIPS workshop will be in Hyderabad from 4-7 March 2018 (applications are now closed for this workshop). Visit our website to find out more about these workshops. In the Public Engagement section, read about the recently held two-day workshop at Darpana Academy of Performing Arts in Ahmedabad that was organised as part of the public engagement project the “Actor Doctor Theatre project” that intends to foster cross-disciplinary exploration of health. This section also includes announcement of our new initiative Superheroes against Superbugs that aims to inform and engage with the public on the emerging threat of antibiotic resistance. IA Fellow, Dr. Abhijit Majumder (IIT Bombay) along with colleagues in Mumbai have launched Curiosity Circle to promote public understanding of science- find out more about this initiative in this issue. Sense about Science and NHS in the UK have developed a fantastic guide for researchers on how to involve the public in working out how to communicate their research – also shared in this section. Through its various programs, India Alliance constantly strives to promote and support international research collaborations and has recently joined “Together Science Can”, a global campaign to encourage researchers around the world to join together to protect the future of vital research collaborations. More information on this campaign has been included in this newsletter.

Inspired by insect wing surfaces that are capable of warding off bacteria including drug-resistant strains, Dr. Jafar Hasan and colleagues at IISc Bangalore have developed etched aluminum surfaces with similar property. Use of such material can help minimize spread of bacterial infections especially in the hospital environment.

Finally, we are pleased to launch IRMI, a new Research Management programme for India, which aims to strengthen institutional ecosystems. India Research Management Initiative (IRMI), will provide a mechanism for enabling research management at institutions in India. Read about this new initiative in this issue.

Prof. Raghu Padinjat (NCBS Bangalore) and his team’s latest research provides new insights into the GPS-like system of cells and its potential implications in neurodegenerative diseases such as ALS, which currently has no treatment.

A big thank you to all those who have contributed to this newsletter.

Latest research from Prof. Annapoorni Rangarajan's lab at IISc Bangalore reveals a novel interplay and role reversal of two crucial cellular proteins in regulating spread of cancer cells. This work provides new therapeutic strategy to control spread of cancer (metastasis).

Special thanks to Prof. Annapoorni Rangarajan for sharing the cover image which shows cancer spheres formed by breast cancer cells.

Dr. Benu Brata Das along with his team and collaborators at IACS Kolkata, have designed a novel and potent compound that selectively kills cancer cells by disrupting their DNA repair machinery.

Find archives of our past newsletters here.

As always, it’s a pleasure to receive your valuable comments and suggestions for the newsletter so please do keep them coming.

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

Finally, Dr. Tavpritesh Sethi (AIIMS Delhi) in collaboration with Dr. Anurag Agrawal (CSIR-IGIB, New Delhi) have used Artificial Intelligence to diagnose and detect Asthma sub-types in children.

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CONTENT 4

India Alliance Fellowships

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India Alliance Recently Recommended Awardees

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New India Alliance Fellows

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India Alliance Fellows’ Research Highlights:

Recently published research of

Dr. Subba Reddy Maddika (CDFD, Hyderabad), Dr. Roop Mallik (TIFR, Mumbai), Prof.Raghu Padinjat (NCBS, Bangalore), Dr. Jafar Hasan (IISc Bangalore), Prof. Annapoorni Rangarajan (IISc, Bangalore), Dr. Benu Brata Das (IASC, Kolkata), Dr. Tavpritesh Sethi (AIIMS, New Delhi)

12 India Alliance Fellow in Spotlight Interview with Dr. Smarajit Polley, Bose Institute, Kolkata

15 Resuming a scientific career after a break Dr. Sonam Mehrotra (ACTREC, Mumbai)

16 India Alliance workshops & events *Report on 1st Developing Indian Physician Scientist (DIPS) workshop, Delhi *Upcoming workshops *Report on Young Scientist Research Symposium

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Public Engagement *Actor and Doctor – Public Health Theatre Festival *Superheroes against Superbugs *Curiosity Circle *Resources for Public Engagement with Science

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Together Science Can Global campaign to promote international collaborations

22 India I EMBO Symposia : Call for applications & recent awards

23 India Research Management Initiative (IRMI) 24 Other announcements Dr. Paul Janssen Award for Biomedical Research

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INDIA ALLIANCE

FELLOWSHIPS Clinical and Public Health Research Fellowships Preliminary application deadline : 07 February 2018 Eligibility

successful in building a track record of pursuing a cutting edge research and wish to establish their own independent clinical/public health research program in India. Suitable for applicants with 4-7 years of relevant experience.

Eligibility limit covers the entire range of Clinical and Public Health Research Fellowship schemes • No age or Nationality restrictions. • The candidates need not be resident in India while applying but should be willing to establish an independent research career in India. • Clinicians and Public health researchers do not require a PhD to apply. • This competition is open for clinicians and public health researchers with up to 15 years of post-MD/MS/MPH/PhD or equivalent clinical / public health research experience. • Applicants are advised to choose the most appropriate scheme suitable for them based on their qualification, research experience, career trajectory and track record. Please refer to the guidance notes, provisions and mandate of the scheme for assessing your eligibility on the website. The Office reserves the right to advice on the suitability of the scheme accordingly. Eligibility guidance notes: Early Career Fellowship: For those applicants who have shown promise to pursue research and wish to further their efforts to build a research career under the supervision of a Fellowship supervisor. Suitable for applicants in the final year PhD/MD/MS/MPH or have up to 4 years of relevant experience

Intermediate Fellowship: For those applicants who have been

Senior Fellowship: For those applicants who have demonstrated their potential to lead an independent research program and want to expand it further to undertake pioneering research. Suitable for applicants with 7-15 years of relevant experience. Provisions: The 5 year Fellowship support provides • interested clinicians the opportunity to pursue their research goals in combination with their clinical duties. • competitive personal support • generous research support with flexibility to accommodate requirements of clinical and public health research. • Flexibility to request additional support staff • Support training cost and research sabbatical • Funds for International training and travel Application process: Application forms are available on the India Alliance online application System (IASys) Please visit our website for further information on the remit, provisions and application process. Write to us at info@wellcomedbt.org

Senior and Intermediate Fellowships in Biomedical Research Preliminary application deadline : 21 February 2018 Senior and Intermediate Fellowships are available across the full spectrum of biomedical research from fundamental molecular and cellular studies through clinical and public health research*. Interdisciplinary projects are also welcome. Eligibility: • No age or nationality restrictions. The applicant need not be resident in India while applying but should be willing to relocate to and work in India. • A salaried position or commitment towards a salaried position at the Host Institution is not required. • Applicant can have a PhD in any discipline of science. • This competition is open for basic science/veterinary researchers between 4 -15 years of post-PhD research experience. • Applicants are advised to choose the most appropriate scheme suitable for them based on their qualification, research experience, career trajectory and track record. Please refer to the guidance notes, provisions and mandate of the scheme for deciding on the scheme you wish to compete for. The Office reserves the right to advise on the suitability of the scheme accordingly. Eligibility guidance notes: Senior Fellowship: For researchers who have demonstrated their potential to lead an independent research program and want to expand it further to undertake pioneering research. Suitable for applicants with 7-15 years of post-PhD research experience.

research and wish to establish their own independent research program in India. Suitable for applicants with 4-7 years of post-PhD research experience. Provisions: The 5 year Fellowship support provides • • •

competitive personal salary support generous and flexible funds for research funds to develop international collaborations

Requirements: The following are essential for the application. • • •

A research proposal that is based on a hypothesis and seeks to answer an original biomedical research question A not-for-profit Host Institution in India that will administer the Fellowship for the full duration of the award A sponsor at the Host Institution, who can guarantee space and resources for the duration of the award

Application process: After the call for application has been made, you can complete the online application form available on the India Alliance online application System (IASys) Please visit our website for further information on the remit, provisions and application process. Write to us at info@wellcomedbt.org

Intermediate Fellowship: For postdoctoral researchers who have been successful in building a track record of pursuing a cutting edge

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* We encourage Clinicians and Public Health researchers to apply in the separate Clinical and Public Health competition (see below)


RECENTLY RECOMMENDED INDIA ALLIANCE

FELLOWSHIP AWARDEES India Alliance is pleased to announce Fellowship Awardees for Basic Biomedical Research Fellowships and Clinical and Public Health Research Fellowships. Interviews for these Fellowships took place in November 2017. Please note, these Fellowship Awards have been recommended by the India Alliance Fellowship Committee. Recommended Awardees, who accept the India Alliance Fellowship, are listed on our Fellows page. * indicates newly awarded Host Institution.

Basic Biomedical Research Fellowships 2017 Intermediate Fellowships November 2017 round

Senior Fellowships November 2017 round

Dr Manikandan Subramanian,Institute of Genomics and Integrative

Dr Vatsala Thirumalai, National Centre for Biological Sciences,

Biology, New Delhi

Bangalore

Dr Tanweer Hussain, Indian Institute of Science, Bangalore

Dr B Krishna, National Brain Research Centre, Gurugram

Dr Ramray Bhat, Indian Institute of Science, Bangalore

Dr R V Shaji, Christian Medical College, Vellore

Dr Manikandan Narayanan,Indian Institute of Technology, Madras Dr H Raghuraman,*Saha Institute of Nuclear Physics, Kolkata Dr Ashwini Hinge,*Interactive Research School for Health Affairs, Bharati Vidyapeeth Deemed University

Clinical and Public Health Research Fellowships 2017 Early Career Fellowships

Intermediate Fellowships Dr Devasena Anantharaman, Rajiv Gandhi Centre For Biotechnology,

Dr Uday Kulkarni, Christian Medical College, Vellore

Thiruvananthapuram

Dr Kirthiga M, *Sri Ramachandra University, Chennai

Dr Anita Chopra, All India Institute of Medical Sciences, Delhi

Dr Pragati Hebbar, Institute of Public Health, Bangalore

Dr Upendra Bhojani, Institute of Public Health, Bangalore

Dr Aastha Aggarwal, Public Health Foundation of India, Delhi

Dr Susmita Chatterjee, Public Health Foundation of India, Gurugram

Senior Fellowships Dr Rupjyoti Talukdar, Asian Institute of Gastroenterology, Hyderabad

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NEW

INDIA ALLIANCE FELLOWS

INTERMEDIATE FELLOW 2016

Clinical and Public Health Research Fellowships

Assessing Equity of Universal Health Coverage in India: From Data to Decision-making using Mixed Methods Dr. Devaki Nambiar

sequences (10s-1000s kb) to segregation of chromosomes into territories, and trans-interactions between domains on different chromosomes has been linked with development, differentiation and disease. Although application of various biochemical, genome sequencing, imaging and polymer modeling methods have significantly improved our understanding of genome organization, the principles governing the three-dimensional organization of genome are just beginning to get uncovered. We are interested in understanding the mechanical basis of genome organization. To address this problem we are using an interdisciplinary approach including protein biochemistry/biophysics, genome wide sequencing based methods (like ChIP-seq, Chromosome conformation capture, MNase-seq and RNA-seq), mass spectrometry to polymer modeling.

Project THETA: Towards Health Equity and Transformative Action in tribal health

The George Institute for Global Health WEBSITE

Dr. Rohit Anthony Sinha As we advance towards the achievement of Sustainable Development Goal 3 for health through Universal Health Coverage (UHC) reforms in various Indian states, prior experience suggests that health interventions tend to privilege already advantaged populations, creating inequality. This research seeks to understand the magnitude of inequalities in coverage of UHC at the state level related to age, sex, place of residence, religion, caste status, tribal status, district, as appropriate, and how they have come about using both quantitative and qualitative research methods. She proposes to make her analysis visual and interactive, so that decision-makers and the public can design actions to make health reform a leveller, rather than perpetuator, of inequality.

Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow WEBSITE

Research is primarily focused on understanding the role of lysosomes and autophagy in the process of hormone secretion. Glucagon is glycoprotein hormone secreted by pancreatic alpha(Îą)-cells and plays a significant role in the pathogenesis of both Type I and Type II diabetes mellitus (DM). Under normal physiological conditions, glucagon secretion is increased and insulin secretion is decreased during starvation to counteract hypoglycaemia in humans via increasing hepatic glucose output. However, in diabetes, glucagon secretion becomes insensitive to both high glucose and insulin inhibition, and contributes to hyperglycaemia. In my current research, I aim to understand and modulate a cellular degradative process known as autophagy to reduce the amount of glucagon content inside the pancreatic alpha-cells which secrete them. We believe that the results obtained from this study would benefit future diabetes research and treatment.

INTERMEDIATE FELLOWS 2016 Basic Biomedical Research Fellowships

Protein-protein interactions of chromatin-bound proteins in shaping genome architecture Dr. Ajaz Ul H Wani University of Kashmir, Srinagar WEBSITE

How different cell types acquire and maintain their identity is a fundamental problem in biology. Cellular identity is determined by the combinatorial expression state of hundreds of genes, which in turn is regulated by three-dimensional (3D) organization of chromatin. Multiscale organization of chromatin ranging from loops between enhancers and promoters (1-1000s kb), formation of Topologically-Associating-Domains (TADs) by contiguous

Mitophagy as visualized in Transmission Electron Microscopy (TEM) with a damaged mitochondrial (red) seen engulfed by an electron dense double membrane structure.

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NEW

INDIA ALLIANCE FELLOWS

Functional interrogation of interferon lambda 4 (IFN-L4) in human health and disease Dr. Sreedhar Chinnaswamy National Institute of Biomedical Genomics, Kalyani

defense against cancer, normal healthy cells detect and eliminate the unfit cells. In our group, we are trying address some of the most critical but unresolved questions related to cell competition such as: How do the cells measure the fitness of their neighbors? What do they effectively measure? And how does the fitnessmeasurement determine the cellular fate? To this end, we are undertaking an interdisciplinary approach, in which measuring forces at the cell-cell and cell-matrix junctions becomes central. Ultimately, we would intend to combine the mechanobiology tools of our laboratory with the conventional molecular biology techniques to elucidate the molecular mechanisms and possibly the guiding principles of cell competition.

WEBSITE The broader question I seek to answer in this project is: What is the function of IFN-λ4 in human health and disease. I am interested to better define the functions of IFN-λ4 as an immunomodulatory cytokine, and seek to answers to the questions: what other cellular proteins does it interacts with? How does the potential to express a functional IFN-λ4 affect the basal antiviral states in healthy individuals? What is the molecular mechanism behind the association of the functional IFN-λ4generating polymorphism with allergic asthma? Does the potential to express a functional IFN-λ4 associate with a less severe dengue disease?

The image depicts how mutant and potentially tumor forming cells expressing an oncogenic version of Ras proteins (green) are physically compacted before getting eliminated by the surrounding wild type cells that do not express this protein. Cell nuclei are shown in red.

The answers to these questions are important to know since human IFN-λ4 is an important and potent antiviral cytokine that is expressed in only a subset of the individuals in any given population. It is expressed out of a frame-shift causing genetic polymorphism that varies in allele frequency based on ethnicity. Its expression is the highest in people of African ancestry, intermediate in the European population and the least in the eastAsian population. Potential to express a functional IFN-λ4 is known to be detrimental in some instances (like hepatitis C virus infections) but beneficial in others (like inflammatory conditions). Defining its functions will allow us to understand several disease and health conditions in humans that the IFN-λ4-generating polymorphism is associated with.

SENIOR FELLOW 2017

Basic Biomedical Research Fellowships

Regulation of host splicing machinery by factors from Mycobacterium tuberculosis and its impact on host innate defense mechanism

INTERMEDIATE FELLOW 2017 Basic Biomedical Research Fellowships

Dr. Dhiraj Kumar

Mechanobiology of cell competition

International Centre For Genetic Engineering And Biotechnology, New Delhi

Dr. Tamal Das

WEBSITE

Tata Institute of Fundamental Research Hyderabad

Among many interesting lines of investigation, we recently discovered, through an inter-disciplinary approach, that infection of human macrophages with Mycobacterium tuberculosis (Mtb) causes massive alterations in the pattern of RNA splicing in the host transcriptome. Further, the alterations selectively targeted molecules and pathways of the innate immune mechanism, which eventually helped Mtb to survive better in the macrophages. Through the India Alliance Senior Fellowship, our main goal is to identify how Mtb could achieve such specific disruption of a highly fundamental process like RNA splicing in the host. This is a tremendously challenging question and I believe the support and flexibility provided by the India Alliance fellowship will enable us to address this exciting aspect of tuberculosis pathogenesis.

WEBSITE

Mutations in the genetic material can have devastating consequences on the integrity of our tissue and organ systems. If remain undetected, mutated cells can compromise the tissue fitness and serve as the cradle for cancer formation. It is, therefore, essential to understand how the tissues in our body, especially the epithelial tissues, maintain their fitness for a considerably long period, in face of incessant spouting of mutated cells. In this respect, cell competition is a fundamental fitness-sensing process. Through cell competition, which is also known as the epithelial

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INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS Role of a tumour suppressor protein in regulating glucose in cells Dr. Subba Reddy Maddika, Senior Fellow

Centre for DNA Fingerprinting and Diagnostics (CDFD) Hyderabad Recently published work from our group has demonstrated a new link between tumour suppressor protein PTEN and SNX27Retromer complex to regulate glucose uptake by cells.

Glucose uptake by most tissues is carried out through facilitated transport mediated by membrane proteins called glucose transporters (GLUTs). Out of 14 GLUTs identified in humans, only four of them (GLUT1-4) have been characterized to be specific for glucose transport. Each GLUT plays a specific role in glucose metabolism dependent on tissue expression and transport kinetics. While GLUT2, 3 and 4 are expressed in hepatocytes, neurons and adipose tissues respectively, GLUT1 is ubiquitously expressed in all the cells of the body and is responsible for basal glucose uptake. For cellular glucose uptake, the cytoplasmic vesicular GLUT1 need to be trafficked to the cell membrane. Translocation of the GLUT1 transporter from cytoplasmic sorting vesicles to the plasma membrane is mediated by retromer (a heterotrimer of VPS26VPS29-VPS35)-SNX27 complex. In our study, we identified an essential regulatory role for tumour suppressor PTEN in controlling GLUT1 recycling to plasma membrane through disruption of SNX27-retromer complex. PTEN is a well characterized tumour suppressor phosphatase found to be deleted or mutated in various cancers. By using an interaction proteomics approach, we identified SNX27 as a novel binding

partner for PTEN in cells. PTEN competes with the binding of SNX27 with its retromer components, specifically with VPS26, and thus PTEN prevents the assembly of SNX27-retromer complex. Subsequently, disruption of SNX27-retomer complex assembly by PTEN results in reduced GLUT1 at the plasma membrane due to defective recycling and thus reduced cellular glucose uptake. PTEN is known to execute its cellular and tumour suppressor functions majorly through controlling AKT pathway via its phosphatase activity. Interestingly, we have shown that PTEN regulates retromer assembly and GLUT1 recycling in a phosphatase and AKT independent manner. Together, our findings reveal a fundamental role of PTEN in regulation of glucose transport and provides an alternate phosphatase independent tumour suppressor function for PTEN in human cancers. PTEN Regulates Glucose Transporter Recycling by Impairing SNX27 Retromer Assembly. Swapnil Rohidas Shinde and Subbareddy Maddika. Cell Reports, 2017 Nov 7;21(6):1655-1666. Banner image (above): Plasma membrane localized GLUT1 detected by staining HeLa cells with anti-GLUT1 antibody followed by confocal imaging

New insights into the regulation of fat secretion from the liver & Hepatitis-C virus replication Dr. Roop Mallik, Senior Fellow

Tata Institute of Fundamental Research (TIFR) Mumbai Our liver secretes fat into blood in a precisely controlled manner despite vast changes in the fat content inside liver. When the liver fails to control how much fat it secretes out, this shows up in our blood report as elevated triglycerides, a cause for much alarm. How the liver controls secretion of fat into blood is unknown but this is crucial for understanding a vast variety of diseases including obesity, diabetes, fatty liver and liver cancer. Our group, in collaboration with scientists from IISER Pune and IISc Bangalore now show that the Motor protein Kinesin actually

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transports fat-containing droplets to the endoplasmic reticulum (ER) in liver cells. This transport engineers physical interactions between the ER and fat droplet, thus supplying fat for secretion from the liver. When we fast (for example, when we go to bed every night) there is massive accumulation of fat in the liver. If the liver secreted all this fat into blood, that would be serious trouble!! To prevent this from happening, the Kinesin motor is removed from fat droplets in Continued on next page‌


INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS fasted state. This reduces fat supply to the ER and tempers fat secretion from the liver in fasted state. This entire mechanism is shown to depend on insulin, explaining how kinesin on fat particles responds to the fed/fasted state of an animal. Further, we show that reducing kinesin also blocks propagation of Hepatitis-C Virus (HCV) inside liver cells. This suggests possible drug targeting of this chronic virus by blocking this Kinesindependent transport of fat droplets inside liver.

Secretion from the Liver. Priyanka Rai*, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S. Kamat* and Roop Mallik. PNAS. November 2017 *Drs Siddhesh S. Kamat (Intermediate Fellow) and Priyanka Rai (Early Career Fellow) are also India Alliance Fellows. Media report: Transport Protein Helps Maintain Amount of Fat in Blood: New Study. India Science Wire

A Kinesin dependent Mechanism for Controlling Triglyceride

Etched aluminum capable of killing bacteria including drug-resistant strains Dr. Jafar Hasan, Early Career Fellow

Indian Institute of Science (IISc) Bangalore

To combat hospital-acquired infections (HAI) or “nosocomial” infection, our research group has etched commercially available aluminum alloys to generate micro- and nanoscale roughness on the surfaces, inspired by insect wing surfaces that ward off bacteria including drug-resistant strains. Antimicrobial resistance (AMR) is a one of the biggest health threats of this century. Microorganisms such as viruses, bacteria, fungi etc. that become resistant to the toxic effects of drugs are called drug-resistant microbes. Drug-resistant bacteria are the cause of many infections in sensitive areas of hospitals in India such as ICUs, operation theatres, hospital beds, sinks, toilets, door knobs, elevator, and other instruments used by doctors and the hospital staff. According to WHO, of every 100 hospitalized patients at any given time, 7 in developed and 10 in developing countries will acquire at least one HAI. This highlights the need for better hospital hygeine practices as well as material that can be used to make bacteria-resistant medical equipment to reduce spread of infections. We have developed etched aluminum surfaces that were found to kill as well as repel wide range of disease-causing as well as drugresistant bacterial strains- 82 % of E. coli, 25 % of K. pneumoniae and 86 % of P. aeruginosa. The etched alloy surface also reduced the number of S. aureus cells to one-tenth of the attached cells on the control alloy surface. In general, the surface roughness induced at microscale was able to resist the bacterial attachment whereas the multi-scale roughness, especially the nanostructures, imparts a bactericidal property to the surface. The fabrication method of etching is also shown to be easily scalable for industrial

applications where larger area of A4 size aluminum sheets were fabricated with the same surface topography. Roughness measurements on the surfaces followed by statistical analysis revealed that specific ranged values of several parameters can yield a highly bactericidal surface; thereby providing the design to make an efficient bactericidal surface irrespective of the method of fabrication. It is predicted that such engineered surfaces with multi-scale topography can help to minimize spread of bacterial infections especially in the hospital environment.

Multi-scale surface topography to minimize adherence and viability of nosocomial drug-resistant bacteria. Jafar Hasan, Shubham Jain, Rinsha Padmarajan, Swathi Purighalla, Vasan K. Sambandamurthy, Kaushik Chatterjee. Materials & Design. November 2017. Media report: IISc: Chemically etched aluminium kills, keep surfaces bacteria-free. The Hindu

GPS-like system of cells and its potential implications in neurodegenerative diseases Prof. Raghu Padinjat, Senior Fellow

National Centre for Biological Sciences (NCBS), Bangalore Living cells are constructed from biomolecules such as proteins, lipids and carbohydrates that are required for normal function. Every cell has a unique composition, i.e. it is put together from a specific set of molecules. In addition, these molecules need to be positioned at the correct locations within the 3D organization in the cell. How does this work and what are the consequences of not placing a protein in the correct location?

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In a recently published study from my group, we investigated the localization of a protein called RDGB that acts as a ferry moving lipid molecules from the interior of the cell to the surface membrane. We studied this in a fruit fly (Drosophila) system. The presence of the correct amounts of the right lipids at the plasma membrane is important for normal cell function. Inappropriate control of lipid levels at the cell membrane results in many human diseases. Continued on next page…


INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS

Genetic disorders such as mutations in the PTEN gene alters the lipid composition of the plasma membrane and frequently results in human cancers. Understanding how molecules such as RDGB control lipid composition may help develop new ways of treating cancers.

Lateral sclerosis (ALS). However, we still do not know why the motor neurons of individuals with ALS undergo degeneration. Studies such as ours provide new insights into why patients with ALS undergo neurodegeneration leading to possible treatments. Presently there is no treatment for ALS.

The study provides an insight into the importance of correctly localizing the RDGB protein. They also identified the components of the GPS system that the cell uses to locate the RDGB protein precisely where it is required.

RDGBα localization and function at a membrane contact site is regulated by FFAT/VAP interactions. Shweta Yadav, Rajan Thakur, Plamen Georgiev, Senthilkumar Deivasigamani, Harini K, Girish Ratnaparkhi, Padinjat Raghu. Journal of Cell Science. November 2017.

Experiments revealed that it is important to correctly localize the RDGB protein to a very unique part of the cell. In the absence of such correct localization the photoreceptor cells do not function normally; in this case fail to respond to light and undergo degeneration. They have found some key parts of the cellular GPS system that help in correct localization and also the signals within the RDGB protein that are read by the GPS system.

Media report- Understanding Positioning System Of Cells May Help Unravel Key Diseases. India Science Wire

One key component of the GPS system that localizes RDGB is the protein VAP. Mutations in human VAP have been identified in cases of the fatal human neurodegenerative disease called Amyotrophic

Banner image description: Confocal microscopy image through the Drosophila retina showing the ommatidia that make up the compound eye. Photosensitive plasma membrane marked with phalloidin is shown in red. The RDGB protein arranged precisely at the base of the plasma membrane is stained in green. At this membrane contact site, RDGB transfers lipids between the endoplasmic reticulum and plasma membrane thus controlling its lipid composition.

Role reversal: Interplay of two crucial cellular proteins in regulating spread of cancer cells Prof. Annapoorni Rangarajan, Senior Fellow IISc, Bangalore

Recent research from our group has demonstrated how two important cellular proteins (and drug targets), Akt and AMPK, undergo a role reversal and interact to regulate the spread of cancer cells, providing a novel therapeutic strategy to control cancer metastasis.

inhibition is necessary for adaptation of cancer cells to survive matrix-deprival. When the detached cancer cells are allowed to reattach, thus mimicking their establishment at the distant organ, Akt is once again re-activated that leads to the concurrent inactivation of AMPK. We further show that two enzymes named PHLPP and PP2C-α mediate this switch between Akt and AMPK signaling. Thus, we have identified a molecular switchinvolving AMPK and Akt that controls the growth and survival of cancer cells during the attachment ↔ detachment cascade in metastasis.

Majority of cancer-related deaths are due to metastasis, a process by which cancer cells spread from the primary site to distant organs. It involves detachment of the tumor cells from the primary site, entry into the blood or lymphatic system followed by their renewed adhesion at a secondary organ where a new tumor is established. However, cell-detachment from the extracellular matrix triggers cell death known as anoikis. Therefore, detached tumor cells must first learn to survive matrix-deprival and then regain attachment to the substratum at the secondary site in order to induce new tumor growth. It is yet not clear how this reciprocal attachment ↔ detachment switch in cancer cells is regulated.

Our work enriches the cancer field by challenging and contradicting the existing dogma in which Akt is required for cell survival and for promoting tumorigenesis whereas AMPK is thought to have a tumor-suppressive function. In our study, we establish a contextual role-reversal for these two proteins in breast cancer progression. This study further predicts AMPK inhibition as a novel strategy to curb metastatic cancer spread. Ironically, the anti-diabetic drug metformin, which activates AMPK, is currently being repurposed for cancer treatment. Our findings raise concern on possible prometastatic side effects of metformin, suggesting that the potential of AMPK-targeting agents in cancer treatment needs further investigations.

Our recently published research shows that two cellular proteins, Akt (Protein Kinase B) and AMPK (5' AMP-activated protein kinase), control this switch by negatively regulating each other. Akt and AMPK are two important cellular kinases that inversely regulate cellular growth and metabolism. Akt supports building up (anabolic) processes required for growth and proliferation, whereas AMPK promotes breaking down (catabolic) processes that result in growth suppression. However, no link between these two proteins was known thus far in cancer metastasis. Our work reveals that the detachment of breast cancer cells triggers AMPK activity that leads to the concurrent inhibition of Akt. This AMPK-mediated Akt

AMPK-AKT double negative feedback loop in breast cancer cells regulates their adaptation to matrix deprivation. Manipa Saha, Saurav Kumar, Shoiab Bukhari, Sai A Balaji, Prashant Kumar, Sravanth K, Hindupur and Annapoorni Rangarajan*. Cancer Research. January 2018

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INDIA ALLIANCE FELLOWS’

RESEARCH HIGHLIGHTS

Novel and potent compound that selectively kills cancer cells by disrupting their DNA repair machinery Dr. Benu Brata Das, Intermediate Fellow

Indian Association for the Cultivation of Science (IACS), Kolkata Our recent work published in Journal of Medicinal Chemistry reports the identification of a novel and potent compound that was shown to be effective in killing cancer cells by disrupting their DNA repair machinery. Cancer is marked by uncontrolled cellular division and growth. Topoisomerase 1 (Top1) enzyme plays a pivotal role by releasing the DNA supercoiling generated during replication and transcription and facilitates cell division. Top1 is a validated target for cancer chemotherapy. Top1 inhibitors, like camptothecin (CPT) and its derivatives, trap Top1 on the DNA to exert its cytotoxicity and are now used for the treatment of metastatic colorectal, pediatric tumors and ovarian cancer. However, these drugs suffer from several limitations including chemoresistance. In the present work, we discovered a novel class of neutral porphyrin compounds that inhibit Top1 without trapping Top1-DNA cleavage complexes, a mechanism which is unique in comparison to the existing Top1 inhibitors like CPT. We provide evidence that in contrast to CPT, the selected porphyrin derivative (we call it,

compound 8) binds reversibly to the free enzyme and effectively inhibits the formation of Top1-DNA cleavage complex both in vitro and in live cells to exert its anticancer activity. We further validated that compound 8 directly targets cellular Top1 using Top1- knocked down breast cancer cells. We show that compound 8 was effective in killing cancer cells by triggering proteasome-mediated Top1 degradation, accumulation of reactive oxygen species (ROS), PARP1 cleavage, DNA fragmentation and apoptotic cell death. Future challenge include animal studies to establish its therapeutic potential. Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes. Subhendu K. Das, Arijit Ghosh, Srijita Paul Chowdhuri, Nyancy Halder, Ishita Rehman, Souvik Sengupta, Krushna Chandra Sahoo, Harapriya Rath* and Benu Brata Das*. Journal of Medicinal Chemistry. January 2018. Media report - IACS researchers use a novel compound to kill cancer cells. The Hindu

Using Artificial Intelligence to diagnose and detect Asthma sub-types in children Dr. Tavpritesh Sethi, Early Career Fellow

All India Institute of Medical Sciences, New Delhi

Advances in genomics and molecular sciences are helping us refine the disease definitions and to tailor treatments. Such ‘precisionmedicine’ or ‘stratified-medicine’ strategies often rely upon discovery of new endotypes, i.e. sub-divisions of a disease. In diseases such as breast cancer, molecular stratification helps doctors to choose drugs and save more lives. In complex diseases such as asthma and diabetes also, clinical experience indicates the existence of endotypes. However, these are much harder to discover because common diseases are also more nuanced (complex). We addressed the challenge of discovering endotypes of childhood asthma by analyzing breath through chemical patterns which are difficult to see by human eye. Since artificial-intelligence and machine-learning have been shown to perform better than humans in complex-repetitive tasks, we used these for pattern discovery.

The study was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi, where children were monitored over a period of five years and the experiments were conducted at CSIR-Institute of Genomics and Integrative Biology., New Delhi At the time of first enrollment, the children breathed into an apparatus that condensed the water-vapor and metabolites in their breath (Exhaled Breath Condensate, EBC), a reflection of their lungs and airway chemistry. EBC was then analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy, a technique commonly used to understand the chemical composition of mixtures. The NMR spectra generated were used to train a machine-learning algorithms (Random Forest) which works like a committee of experts, evaluating a candidate as asthmatic or non-asthmatic and further dividing asthma into endotypes. These endotypes were learnt by the computer without expert input and served as a

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snapshot of airway chemistry at enrollment time. While these endotypes of asthmatic children did not differ in severity of disease at enrollment, they had markedly different 5year incidence of breakthrough exacerbations despite being on treatment. This not only expands our understanding breathchemistry associated with long-term exacerbations in asthma, but also suggests the potential of deciding treatment strategies tailored to the discovered endotypes to improve outcomes in childhood asthma. Exhaled breath condensate metabolome clusters for endotype discovery in asthma. Anirban Sinha, Koundinya Desiraju*, Kunal Aggarwal*, Rintu Kutum, Siddhartha Roy, Rakesh Lodha, S. K. Kabra, Balaram Ghosh, Tavpritesh Sethi and Anurag Agrawal *contributed equally


INDIA ALLIANCE

FELLOW IN SPOTLIGHT

Dr. Smarajit Polley Intermediate Fellow Bose Institute, Kolkata

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

distinct paradigm of kinase regulation.

Molecular processes within a unicellular or multicultural organism is precisely regulated with bidirectional control. Protein molecules inside the cells are often modified even after they have been made, which is known as post-translational modification; examples of which include phosphorylation, methylation, acetylation etc. Reversibility of these modifications are highly coordinated and tightly regulated. For example, while protein enzymes catalyze addition of a phosphate group on to its substrates (phosphorylation), phosphatases remove them (dephosphorylation). A critical balance and precise regulation of these two classes of enzymes help maintain the ‘healthy’ phospho-proteome of a cell/organism. Loss of this balance might have disastrous consequence on the well-being of those cells or the organism as a whole. And, my laboratory is primarily interested in understanding the behavior and functions of protein kinases. Human genome encodes for more than 500 protein kinases, many of which serve as the therapeutic intervention point in a number of disease scenarios. Some of these kinases show complex behavior; they play both beneficial and harmful roles in our body depending upon the situation. In our group, we are trying to decipher biochemical and structural basis of regulation of two such kinase systems using interdisciplinary experimental approaches. Inhibitor of kappaB kinase (IKK) is known to regulate a number of cellular pathways in response to diverse extra-cellular stimuli ranging from pathogenderived substances to inflammatory cytokines, to antigens, to metabolic and genotoxic stresses. IKK-activity is very tightly regulated in cells, that become apparent only on demand in specific situations. Aberrant IKK-activity is associated with a large number of human diseases. However, efforts to develop IKK inhibitors of clinical relevance achieved little success. Active-site directed inhibitors are highly potent but inhibit IKK-activity indiscriminately without any regard to its beneficial roles. It is desirable to design inhibitors that will block aberrant activity of IKK without affecting its protective role. As the importance of higher order assemblies in signal transduction is becoming increasingly clearer, it will be beneficial to realize the structural and biochemical differences between the IKK-complexes (minimal and higher order), before and after induction by a stimulus. Targeting novel protein:protein interaction interfaces in the activated complex may lead to better clinical outcomes. Specific inhibition of activated IKK-kinase will help better tackle autoimmune diseases and cancers. Another line of interest in our lab involves understanding the activation and regulation of the Dual Leucine Zipper Kinase (DLK) MAPKKK, which is essential for regeneration and degeneration of adult nervous system. Prolonging the Dual Leucine Zipper Kinase (DLK)-activity may lead to beneficial effect on neuronal regeneration after injury. This part of the study is undertaken in collaboration with another IA fellow, Dr. Anindya Ghosh Roy at NBRC. Though we are not actively designing drugs, I am hopeful that our studies will help design potent and safer molecules to control two

What motivated you to become a scientist? I was born in a small village in West Bengal, and had a very relaxed childhood. Education system at that time in the village was not very structured, in the sense that we didn’t have to go to tutors or special classes etc. Teachers in the school were more like extended family, and we could approach them for anything and everything. They would often tell us stories related to lives of scientists and their discoveries around the globe. Those stories related to Galileo, Einstein, Gauss, Pasteur, J.C. Bose, P.C. Ray, Ramanujan, C.V. Raman, S.N. Bose and many others would have me engrossed and exhilarated. The effect: I fell in love with science along with literature. In addition, the atmosphere in my family was also not very strict to focus on a particular career path. I had the liberty to choose my own path, though my parents had their secret dreams --they never imposed it on me. Also, I had my uncle (maternal) doing his Ph.D. at that time who was my idol. He inspired me and all my cousins a lot, and that had a permanent carving on my being to desire to become a scientist. But still I was not sold to the idea of becoming a scientist when I left school. As a teenager, I wandered in my mind whether to become a scientist or a doctor or an engineer or a journalist or to join Indian Navy or Air Force or Administrative Services. It was in college that I met the Cat (Schrodinger’s), and I knew I wanted to be a scientist. As you can see, biology was not my first love; it was physics. But I became a biologist who uses principles and methodologies related to physics (X-ray, cryo-EM, mass spectrometry). This change is a different story, and I shall keep it for a different occasion. Bose Institute is celebrating its centenary year. As an alumnus and current faculty at Bose Institute, can you tell us about how the institute has helped shape your scientific journey so far? In the last section I talked about how I made up my mind to become a scientist, but I didn’t tell you what kind of science. During my MSc days, due to a specific bend of mind (seeing is believing!), I wanted to do structural biology. I wanted to find out what exactly the term ‘conformational changes’ meant that popped up so many times in the class room. What change? How does it look, in two different states? So, I joined MBU, IISc Bangalore as a graduate student. However, due to some unavoidable circumstances back home I came back to Kolkata and joined Bose Institute for my Ph.D.

Acharya Jagadish Chandra Bose, one of the most eminent visionaries of modern India, established Bose Institute in 1917. The institute was dedicated to pursue cutting edge research for investigating, in Acharya’s own words, "the many and ever opening problems of the nascent science which includes both life and non-life". Continued on next page…

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INDIA ALLIANCE FELLOW IN SPOTLIGHT

Dr. Smarajit Polley

Bose Institute continued to enrich scientific achievements of modern India ever since its inception in different areas of science ranging from theoretical astrophysics to experimental biology. The legacy of the institute continues till date with the accumulation of an impeccable group of young and experienced scientists with varying interests and expertise. I have always found Bose Institute as a place with an encouraging academic aura that fosters multidisciplinary collaborative research. It has a thriving intellectual atmosphere that brings together people from different walks of science in pursuing common interest to solve a complex problem. Throughout my tenure at the Bose Institute, I have enjoyed the company of scientists with different interests and expertise. I have always been enriched by interactions with scientists from completely different fields, and in many cases, they introduced new turns in my thinking.

At the organism level, I find neuroimmunology fascinating. Our nervous and immune systems are by far the two most important aspects of the process called life. For a long time, it was thought that they worked independent of each other without any apparent dialogue between them. However, for the last two decades or so the concept has been changing, and more and more evidence is available to show that they do interact and their interaction plays and important role. Though I have not actively plunged into this area, I hope to do so in future. As you can realize, it has to be a truly multi-disciplinary and multi-lab effort to jump into this area, and I am constantly in conversation with a few of my peers here in India about the possibilities. As it so happens, we all are busy working towards our immediate goals in the realm of our current research programs. Hopefully, we shall find the right moment suitable for ourselves to delve deeper into this area of research.

I remember my thesis mentor telling us how it was more important to keep an alert eye on the experimental design and details than on the result it produces. A great result from a lousy experiment was the last thing one should look for. As a researcher, I follow this mantra. It is at Bose Institute that I learned of dreaming big amidst odds. It is where I learned, success in scientific research is rather a state of the mind, more philosophical and personal than something that could be measured with any metrics.

At the molecular level, the overall aspects of regulation of eukaryotic gene expression constantly intrigues me. Be it regulation imparted by the non-translatable RNA molecules (like lincRNAs) or transcription machinery (transcription factors and their mutants, for example WT and GoF mutants of p53; epigenetic changes etc.) or developing synthetic gene regulatory circuits that respond to chemical cues in a designed/predictable fashion (i.e., to combine structural, chemical and synthetic biology). Apart from the very last one, I think, my group will be able to participate and contribute to the other two areas in the near future given our expertise in structural and chemical biology along with our deep understanding of biochemistry.

Apart from doing science confined in a lab, the Institute fosters the philosophy of spreading biotechnology tools and measures in the rural areas that either help solve a local problem or help locals manage these difficulties and make a better livelihood. Is there a research area other than yours that interests you deeply and that you would like to perhaps integrate in your current research? First of all, let me tell you briefly about a few things that excites me beyond my current research program. These would be, not in any particular order of preference, neuroimmunology, RNA biology, regulation of transcription.

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What is on your wish list this year as a scientist? We are going to move to a brand new Unified Academic Campus of Bose Institute in a new location. So, my wish is that we have all the experiments start and run smoothly in the lab at the new location. I hope that we have some of our biological complexes ready for crystallization as well cryo-EM studies. I wish a few more cryo-EM facilities come up in India so that we as a community can survive and thrive in the game internationally. Continued on next page‌


INDIA ALLIANCE FELLOW IN SPOTLIGHT

Dr. Smarajit Polley

How has Wellcome Trust/DBT India Alliance funding helped you and your research? Based on your experience, any advice for those applying for India Alliance Fellowships? Let me tell you the truth. Without the support from the India Alliance I would not have been able to do much, not even dream of doing what we are trying to do in the lab. Our aims are challenging, high risk. I was lucky to have convinced the IA to fund this project. I see many of my peers who have done very well and back in India without such fellowships struggling a lot to pursue what they thought of doing. I saw a lot more of them suffering when such funding scopes were not there. I believe many of them would have excelled beyond what they have achieved had they been a recipient, or had such a scheme started in their time. Many of the research approaches that we are trying at this moment require materials that are highly specialized and expensive. I would have possibly not thought of approaching this problem in the same scale or in the same way that we are doing right now if I did not receive this funding. The alternatives would have been inadequate to do justice to the inherent complexity of the problem at our hands. I must confess at this moment that I am not a die-hard fan of any particular experimental technique; I am sold to a problem, and ready to try anything and everything to find an answer (or a clue, for that matter). And, this funding allows me try all those different options. To a prospective applicant, my suggestion is to be yourself and be

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daring. What you have done so far must have been great and productive, and in some cases, may have been routine (may not have been a mundane business when you started, but time has changed). So, you can be adventurous, yet remain logical. Something that seemed impossible when you were a postdoc is not necessarily so at the time of your application or in the near future. You must be aware what is going on around, not just in your field but in other areas, such that you can apply the big leaps coming in other fields in your own research. You must give an idea that you are able to handle a challenging and intriguing problem, and are not afraid of taking risks and of failures associated with a challenging problem. What keeps you going every day? My family, friends and the eagerness to learn something new. Also, a strong desire to do something that is going to be useful in dealing with some/any of the daunting biomedical problems that are still enigmatic. I believe this eagerness to learn keeps me on my toes and provides the impetus to do good science. Sometimes I don’t get results, but the learning process still makes me feel happy. Scientific problems where path to success is not apparent or easily discernible gives me the much-needed kick. Sounds obscure? Can’t help, that’s how I am. In many such cases the path is long, but the journey is enchanting (if one can endure it). I believe ‘what doesn’t kill you makes you stronger’. Cheers!


Resuming a scientific career after a break Dr. Sonam Mehrotra Intermediate Fellow ACTREC Mumbai This article was originally posted on IndiaBioscience. This article is part of their ongoing “Journey of Young Investigator (JOYI)” series To succeed in academia is hard for anyone. It becomes even more challenging if one takes a career break to take care of family needs or due to any other personal circumstances. Is it possible to return to a research career after a prolonged break and still be successful? From my own experience, I can say, it is possible but is definitely not easy.

I returned to research after a gap of almost two years as a Scientist-D at the Centre for Excellence (CoE) in epigenetics at IISER Pune. I started working on projects related to the CoE’s objectives and also developed my own independent research project with support from my grant. There had been significant technical advancements in my field while I was away from the bench. Initially, I felt nervous and wondered if I would be able to execute and design successful experiments. After joining the IISER Pune, the first thing I tried to do was to interact with PhD students and postdocs in the lab and re-train myself in current technologies and research methods. My association with the CoE and IISER Pune helped me in a big way to update my existing research skills and regain confidence. My advisor and mentor at IISER Pune encouraged me to apply for the Wellcome Trust/DBT India Alliance (India Alliance) Intermediate Career Fellowship. Initially I was quite hesitant, but on realising that this exercise would at least help me prepare a good grant proposal, I applied for the fellowship. I was fortunate that the fellowship was awarded to me and I got this opportunity to begin independent research once again.

Unlike other Principal Investigators (PIs), I became one after a significant unintended but a circumstantial gap in my scientific journey. Though I did not go to the lab while on this socalled “break”, I could not really keep myself away from science. I thought about alternate career options but did not find anything more interesting than a career in research. So, I tried to keep in touch with new developments in my field by regularly browsing through new journal articles and talking to friends who were pursuing research. During my PhD and post-doctoral studies in the U.S, not only did I gain extensive research experience, I also got a chance to involve myself in writing several grant applications with my mentors. This experience in grant writing proved to be a crucial factor in helping me resume my scientific journey after a break.

I moved to ACTREC a year ago and started working with a small research group comprising of a research fellow, a postdoc and a few trainees. The India Alliance fellowship has given a great boost to my scientific career. I have managed to re-enter the academia, but I still have to pass the test of time, publish quality science and achieve my scientific goals. As I continue on my journey, I feel immensely grateful to my mentors, family and friends because of whom I did not give up and quit science.

I constantly looked out for any re-entry schemes that could offer me a route to re-enter academia in India. Eventually, with the help and support from a senior Principal Investigator who sponsored my grant application and provided me space in his laboratory two of my applications were accepted. I was awarded fellowships, one each from Department of Biotechnology (DBT) and Department of Science and Technology (DST). As I could avail only one of these at a time, I chose the BioCARe fellowship sponsored by DBT.

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INDIA ALLIANCE

WORKSHOPS REPORT

Developing Indian Physician Scientists (DIPS) workshop 23-26 November 2017, New Delhi

The first Developing Indian Physician Scientists (DIPS) workshop, with an aim to ignite scientific curiosity in young doctors, was held at CSIR-Institute of Genomics and Integrative Biology (IGIB), Mathura Road, New Delhi from 23-26 November 2017. The workshop held over four days, introduced 36 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, Prof. M. K. Bhan, Dr. Samir Brahmachari, Dr. Sundeep Salvi, Dr. Vinod Scaria, Dr. Shinjini Bhatnagar, Dr. Koundinya Desiraju, Dr. Debojyoti Chakraborty, Dr. Sridhar Sivasubbu, Dr. M Faruq, Dr. U Mabalirajan and Dr. Mani Subramanian Dr M.K. Bhan, President JIPMER, former Secretary of Department of Biotechnology (DBT), Government of India, and an inspirational physician-scientist talked to the attendees on his research journey. Dr Samir Brahmachari, former Director General of Council of Scientific & Industrial Research (CSIR), delivered a strong message

of the dire need for physicians-scientists. Dr. Sundeep Salvi in his talk explored his views on importance of asking the right questions in the field of research. He emphasized that, without the right question, the time and all the other inputs into research become futile. Without a right question, it is not possible to design a study. Dr. Rakesh Aggarwal, Professor, Department of Gastroenterology, SGPGI, Lucknow and a well-known epidemiologist introduced the fields of epidemiology and research. He also alluded to the fact that one needs to consider issues like inherent variability in experiments, bias and confounding, while designing the experiments. Dr. Anurag Agrawal, Director, CSIR-IGIB, discussed Artificial Intelligence, and how this has already started to have an impact on the practice of medicine. In addition, he facilitated an online lecture by Dr. Atul Butte, on the availability of immense stores of free data for research, and how these routinely-collected data could be used for understanding biomedical processes. An important aspect explored by the faculty was the field of genomics and genetic engineering by Drs Vinod Scaria and Debojyoti Chakraborty. On the first day, the participants were given a tour of a genomics facility. Also, they were taken around the data processing facility of IGIB to give them an idea of the type of processing power and storage capability needed for genomics work. The idea to sequence, remove or insert a new gene in the genome has given new hopes. Many clinical conditions that previously remained undiagnosed can now be fully understood in terms of causation and pathogenesis; in some cases, an understanding of the pathogenesis also opens new vistas for treatment, early diagnosis such as through ante-natal diagnosis, and prevention of serious illness. New technologies in gene editing involving CRISPR technology to create new animal knockout models for the field of experimental biology has enabled the study of role of genes by creating various knockout mice and zebrafish models. The field of experimental biology and the role of yeast, zebrafish and other animal models was introduced on the last day. They also toured the zebrafish facility and had an opportunity to see development of zebrafish starting from a fertilized ovum to an adult. Mouse models were discussed in detail, especially models of respiratory and cardiac disease. In particular, the participants were shown the thinking behind model development and, with advantages and limitations, using asthma as a focus topic Overall the attendees showed great enthusiasm throughout the workshop with active discussions. Online groups were made at the end of the conference for further interaction. The last day will be changed between workshops. The next DIPS workshop will be held at CCMB, Hyderabad from 4-7 March 2018. Applications for this workshop is now closed. The Developing Indian Physician Scientists (DIPS) workshops have been designed by Dr. Rakesh Aggarwal and Dr. Anurag Agrawal and facilitated and supported by the Wellcome Trust/DBT India Alliance.

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INDIA ALLIANCE UPCOMING WORKSHOPS

SciComm101 @ BARC, Mumbai – 3 February 2018 Developing Indian Physician Scientists (DIPS) workshop – 4-7 March 2018 SciComm101 @ Ahmedabad University – 8 March 2018 EMBO Research Leadership Course – 19-22 March 2018 I Delhi ; 26-29 March 2018 I Hyderabad 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 EVENT REPORT

Young Scientist Research Symposium 9 November, IIT Madras PhD students and postdoctoral researchers working in the labs of India Alliance Fellows were provided a platform to showcase their work, interact with India Alliance Selection Committee Members, and strengthen their professional networks at the 1st Young Scientist Research Symposium on 9 November 2017 at IIT Madras. The symposium was supported and facilitated by the India Alliance and hosted by Department of Biotechnology, IIT Madras.

Young scientist talks

Poster presentations & Panel discussions

The symposium included expert talks by India Alliance Committee Members, oral presentations by young scientists, poster presentations, and panel discussions on grant writing and the interface of basic and clinical research.

Expert talks were given by Prof. Douglas Young (The Francis Crick Institute, London, UK), Prof. Mohan Balasubramanian (University of Warwick, UK) and Prof. Shyni Varghese (University of California at San Diego, USA). In addition to talks by experts and young researchers, Prof. Noel Buckley (University of Oxford, UK), Prof. Shankar Subramaniam, (UCSD, USA) and Dr. Shahid Jameel (CEO, India Alliance) shared pointers on writing good grants. Finally, Prof. Ajit Lalvani, Imperial College, UK facilitated an important discussion on the importance of collaborations between basic and clinical research, with Prof. Irwin Nazareth (UCL, UK), Prof. Sudhir Krishna (NCBS Bangalore), Prof. David Osrin (Institute of Child Health, UCL, UK) and Prof. George Griffin (St. George’s Hospital, UCL, UK).

Mr. Bapu Koundinya Desiraju, CSIR – IGIB, New Delhi

Dr. Srishti Dar, TIFR, Mumbai

Dr. Harish Katti, IISc, Bangalore

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Ms. Sakshi Malik, THSTI, Faridabad


INDIA ALLIANCE

PUBLIC ENGAGEMENT

Workshop report

Actor- Doctor Staging Public Health Matters The implementation of India's first Public Health Theatre Festival started off with a two-day sensitization workshop held on the 16th and 17th December 2017 at Darpana Academy of Performing Arts, Ahmedabad. 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 main stakeholders were 15 theatre directors ranging from drama groups at National Institute of Design and Indian Institute of Management (IIM) Ahmedabad; first-time directors like doctors and researchers with decades of experience in healthcare systems and community outreach efforts and finally purely entertainment based theatre groups.

Health, Mental Health and seasoned theatre activists who have been using theatre as a device for reaching out to the community. This was followed by screening of the film by Dr. Sharma, 'The Code' on Obsessive Compulsive Disorder (OCD) which was recently awarded the best film in the Docu-drama health film category at the Global Nature Film Festival, New Delhi. This was followed by a discussion on the importance of building entertaining healththemed plots for engaging as well entertaining the audience. After a rigorous Day 1 of absorption for the participants; Day 2 gave them the chance to implement their learning in a full day theatre workshop on Augusto Boal Forum Theatre Technique with Dr. Radha Ramaswamy of Centre for Community Change and Dialogue, Bangalore. A well-respected Boal practitioner in the area of health humanities and social behavior change through theatre.

The first day of the workshop started with Dr. Mallika Sarabhai taking the participants through Darpana's rich history and how Shrimati Mrillani Sarabhai innovatively changed the mindset of the society towards women empowerment and dowry deaths snowballing then Prime Minister Jawaharlal Nehru's inquiry into the matter, along with an audio-video on how Darpana through different projects has been using street plays in local communities for reproductive health awareness. Dr . Kartik Sharma, who conceptualized the project, is a public health researcher and Principal Investigator of the project; took the participants through key concepts of Health Communication and Promotion, with case studies on his previous work and social marketing concepts on the lines of 'Nudge' and 'Thinking Fast and thinking slow. In the following session Mr. Jignesh Patel a theatre instructor at Darpana and coordinator in the project assigned lottery selected individual health topics to the participants followed by interactions with Health experts in Cardiology, Reproductive

Dr. Radha Ramaswamy (L) with workshop participants

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. The Public Health Theatre Festival is to be organized in the second week of February and the doctors and actors are currently playing their parts for setting up a show for the audience on the shores of Sabarmati river in Ahmedabad.

Click here to find out more about this project. By Dr Kartik Sharma Project Lead, Actor-Doctors: Staging Public Health Matters

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INDIA ALLIANCE PUBLIC ENGAGEMENT

Superheroes against Superbugs Engaging with the Public to tackle the threat of Antibiotic Resistance The global challenge of antimicrobial resistance (AMR), particularly resistance to antibiotics, has been looming large and threatening to turn infectious diseases into humanity’s biggest killers once again. If the current trend continues, estimates put the death toll due to AMR at 10 million a year by 2050, more deaths than due to cancer and diabetes combined. This single statistic drives home the gravity of the situation and the necessity to tackle this issue urgently. Inappropriate use of antibiotics, both overuse and misuse, is a major contributor to growing resistance. There is, therefore, an urgent need to spread awareness, especially in a country like India where there is relatively higher incidence and greater levels of antibiotic resistance due to easy availability and higher consumption of antibiotics. The World Health Organization issued a Global Action Plan on Antimicrobial Resistance (GAP-AMR) in May 2015 to help countries take concrete steps against this threat. The National Action Plan against AMR of the Government of India released last year aligns with GAP-AMR and emphasises the importance of community action in addressing the threat posed by antibiotic resistance. The Superheroes against Superbugs (SaS) program powered by the India Alliance aims to engage with the general public to increase scientific understanding of antibiotic resistance, to improve awareness of this global threat and build a society of smart antibiotic users. Engagement will be through various mediums such as social media, creative workshops, arts, theater and discussions. In addition, Superheroes against Superbugs school engagement

program aims to promote awareness about antibiotic resistance in school children to develop a future generation of scientifically literate antibiotic users. These school workshops will comprise of interactive games and creative activities around antibiotic resistance as well as discussions with scientists and doctors working in this area. Participating children will be encouraged to innovate and create novel concepts on the issue (comic book stories, mobile apps, video game, virtual reality videos, short films etc.) that will be developed into tools. Both, the activities and the tools, will be made available to everyone to create further awareness around antibiotic resistance. India Alliance invites its Fellows and others to become ambassadors of Superheroes against Superbugs by contributing in any way they can. Those interested in contributing to this important and urgent cause are requested to write to us at public.engagement@wellcomedbt.org Superheroes against Superbugs emphasises the need for the general public to become superheroes as much as we need our scientists and doctors to fight this century’s biggest health threat, by improving our understanding of antibiotic resistance so that appropriate measures can be taken at an individual and community level. Read here to find out why “everyone needs to be an antibiotic resistance fighter”. Join Superheroes against Superbugs

Curiosity Circle To Promote Public Understanding of Science Humans are inherently curious. A kid explores everything till they find a satisfactory answer, even if their so-called satisfactory answer might not be true. As they grow up, their answers become more accurate and are based on scientific evidence. However, they also experience a trade-off as they go through school, they are taught in a way that makes them less curious. Ideally, by gathering more facts and evidence, the child should shed their old ideas, embrace new ones by asking more questions. Any hindrance to this process is detrimental for their intellectual growth and well-being. Same is true for the society. Society, with progress in science, must question its old beliefs, ask new questions to find new answers. Any hindrance in this process will thwart the growth of human civilization. Curiosity Circle, Mumbai or CC, Mumbai aims to play a role in rejuvenating our curiosity, once again. CC is a platform that will bridge the gap between scientists and the society. It plans to bring people from different walks of life to a common arena where they are free to question old beliefs, ask new questions and explore new answers together. The idea germinated from India March For Science that was held in August 2017 which had two major goals increase government funding for scientific research and to stop the spread of pseudo-science. A few of us gathered afterwards and

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collectively felt that both these goals can be achieved by spreading the true spirit of evidence-based science and foster scientific temper among the masses. Keeping this goal in mind, Curiosity Circle was formed.

The present organizing group, which is absolutely informal in its shape and size, includes around 5-6 scientists and 4-5 young science enthusiasts. We aim to organize scientific talks on contemporary scientific and social issues every second Saturday of the month, followed by intense interaction between the audience and the speaker. We hope that such interaction will give rise to more questions than it will answer. As Prof. Nagarjuna, TIFR, Mumbai, told to Hindustan Times, “This is an effort to promote a culture of scientific thinking among people, most importantly among the ‘non science’ community as most people think of science as just facts and information. But, there is so much that is changing about the way we already know things in science.” With this aim, we will post blogs by the speaker and the full video of the talk and discussion after each session to reach the wider audience. We also plan to rotate the meeting at different places so that people from different areas of Mumbai can easily attend. Continued on next page..


INDIA ALLIANCE PUBLIC ENGAGEMENT

Curiosity Circle In the first ever session of CC that was held recently at Homi Bhabha Centre for Science Education, TIFR, Mumbai on 13th of January, 2018. Prof. S.G. Dani, (TIFR (retd.), IITB (retd.), UM-DAE Centre for Excellence in Basic Sciences, Mumbai (present)) spoke about "how the potential of scientific thought may be nurtured, for the good of all". The talk was attended by more than 70 people including school children.

CC is a not-for-profit effort by an ever-expanding group of people and the activities are sustained with the help of well-wishers. We hope that in near future it will spread to other cities too.

To follow our activities and video of the first talk, visit our website , Facebook page or write to us at curiositycircle.mumbai@gmail.com

By Dr. Abhijit Majumder, India Alliance Early Career Fellow Assistant Professor, IIT Bombay

Prof. S.G. Dani giving the first CC Mumbai talk

Resources for Public Engagement with Science

A practical guide developed by Sense about Science and NHS in the UK, “for researchers on involving the public in working out how to communicate findings - from the earliest stages of projects, and on the most challenging of subjects.� Click here to download the guide.

If you have a novel and creative public engagement idea, we would love to hear from you. Please write to us at public.engagement@wellcomedbt.org

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The Wellcome Trust/DBT India Alliance has joined the global campaign “Together Science Can” to promote and celebrate international collaboration in science. Launched last year, Together Science Can encourages researchers around the world to join together to protect the future of vital collaboration.

can speak up for science during key global events.

Collaboration across borders makes science work better and faster. Solving complex problems such as epidemics, the growing burden of dementia, and climate change relies on the best ideas, wherever they come from. But world events threaten the environments within which collaboration thrives, creating an uncertain future for researchers. Together Science Can unites researchers and institutes from across the world and the full spectrum of sciences to mobilise political and social support for global scientific collaboration. It’s a partnership between Wellcome Trust (UK), Wellcome Trust/DBT India Alliance, Royal Society, Helmholtz Association, Max Planck Society, “la Caixa” Foundation, Novo Nordisk Foundation, Wallenberg Foundations, J&J Innovation, Global Health Technologies Coalition and African Academy of Sciences/Accelerating Excellence in Science in Africa.

The campaign calls on researchers to come together with colleagues in their labs or across their organisations and join hands in a gesture that signifies partnership. Dedicated Together Science Can Instagram and Twitter pages will celebrate and champion these partnerships, showcasing the stories that are helping to tackle major global challenges. Researchers and supporters are also encouraged to sign up via the campaign website (togethersciencecan.org), creating a network that

"India Alliance has joined this campaign because we believe that science is collaborative, participatory and makes most sense when it solves real problems for real people. We have also joined this to give leadership opportunities to our researchers. Only enlightened leadership will take forward science, and through it, development both locally and globally." Dr Shahid Jameel, CEO, Wellcome Trust/DBT India Alliance. Dr Jeremy Farrar, Director of Wellcome, said: “Together science can tackle some of the biggest global challenges of our time. But creating barriers betrays the foundations of science, which should be about the exchange of ideas across borders, and we must speak up to prevent this. We can do so much more when we work together, and that includes influencing the decisions that affect scientific progress.” To find out more about Together Science Can visit the website: https://togethersciencecan.org/ Together Science Can can be found on social media using #TogetherScienceCan, or on: •Instagram: @togethersciencecan •Twitter: @togetherscican •Facebook: Together Science Can If you have ideas, issues and/or stories that you would like to highlight through this campaign, please get in touch with us at public.engagement@wellcomedbt.org

Thank you everyone who have extended their support for the campaign so far. Seen above (L-R) Dr. Zahid Kamal (IA Fellow, National Centre for Cell Science, Pune), Dr. Shyni Varghese (IA Fellowship Committee member, Duke University, USA), Dr. Shadhidhara (Indian Institute for Science Education and Research Pune), Dr. Nick Grant & Dr Anne Wozencraft (Cancer Research UK) with Dr. Shahid Jameel (CEO, India Alliance), Dr. Ellen Carpenter (National Science Foundation, USA)

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Application deadline: 15 February 2018 About India I EMBO Symposia The Wellcome Trust/DBT India Alliance and European Molecular Biology Organization (EMBO) will jointly fund up to three meetings per year in India. The meetings should address discovery and innovation through an interdisciplinary approach, with the speakers and participants discussing important global challenges in the context of the life sciences. The meetings should be small, with 10 – 15 highly acclaimed international speakers and 50 – 75 participants, allowing early to mid career scientists to interact with leading international experts during a period of three days. Proceedings from the meeting should be drafted as a position paper to advise the India Alliance regarding this area of research. The paper should in particular outline if and how research covered by the meeting could be beneficial to India. India Alliance may consider increasing funding for research in that area following expert advice and review. Benefits • The maximum funding available for an India | EMBO Symposia is 60,000 euros. • EMBO also supports the organizers and meeting in the following ways: • EMBO creates a dedicated meeting webpage, including registration and abstract submission forms. • EMBO provides a poster and advertising in selected print and social media channels. • Organizers can apply for funds for an EMBO Young Investigator lecture, EMBO Science Policy lecture and EMBO Women in Science lecture. Eligibility • India | EMBO Symposia must take place in India, but scientists from anywhere in the world are eligible to apply, independent of their nationality. • India | EMBO Symposia must cover frontier, pioneering and interdisciplinary areas of life sciences that are underserved in India, and include speakers with interdisciplinary expertise. Furthermore, the application should include a list of (mostly) confirmed speakers.

• For detailed information on the eligibility criteria, including the format of the meeting, please consult the application guidelines (pdf). Please note: After the meeting, the organizers must provide a position paper on the theme that includes a plan to catalyze research in that area in India. India Alliance may consider funding research in that area following expert advice and review. Application process

• The deadline for applications for meetings taking place between the 1st of January 2019 and the 31st of December 2019 is 15 February 2018, 14:00 CEST. • Applicants will be asked to complete an online and an offline application form. • All incoming applications are screened to ensure eligibility requirements are met. • The decision on which proposals receive funding is jointly made by the EMBO Course Committee and the India Alliance Meetings Committee in May. • All applicants are informed of the outcome of their application by email shortly after the committee meetings. Selection process The selection process involves the following steps: • All incoming applications are screened to ensure eligibility requirements are met. • The decision on which proposals receive funding is jointly made by the EMBO Course Committee and the India Alliance Meetings Committee in May and October. • All applicants are informed of the outcome of their application by email shortly after the committee meetings. For detailed information on the application process, key dates, format of the meeting and required documentation, please consult the application guidelines or visit India | EMBO Symposia website. Contacts: workshops@wellcomedbt.org (for questions related to the proposal) courses_workshops@embo.org (for technical questions related to the application system)

The India Alliance and EMBO are pleased to announce the awards for the India I EMBO Symposia 2018 Big Data in Biomedicine (registration closed) 25-27 February 2018 Organisers: CSIR-IGIB, New Delhi RNA viruses: Immunology, pathogenesis & translational opportunities (click on the link to register for the meeting) 28-30 March 2018 Organisers: THSTI, Faridabad From synapses to memory: RNA based regulatory mechanisms (click on the link to register for the meeting) 15-18 October 2018 Organisers: NBRC, Manesar

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The Wellcome Trust/ DBT India Alliance announces the launch of IRMI, a new Research Management programme for India, which aims to enhance institutional ecosystems. IRMI, or India Research Management Initiative, will provide a mechanism for enabling research management at institutions in India. Effective research management helps institutions navigate the high demands for funding, outreach and governance of research. It spans activities that support research, such as national and international funding opportunities, science communication, policy and regulatory matters and intellectual property. India currently lacks a well-developed research management base, which IRMI hopes to address. Good Research Management requires a diverse set of skills and capabilities at the boundaries of research and other disciplines, including business and communications. Individual research managers need training and career progression opportunities to develop the varied attributes of successful research management. IRMI will provide opportunities for research managers in India to receive training and also create a network of practitioners for serving broader career development needs. A Research Management Consultant working with India Alliance would lead the IRMI effort. “We believe that efficient research management structures are needed for Indian institutions to become globally competitive. This initiative aims to catalyze that. It also supports our mission of building excellence in Indian science.” Dr. Shahid Jameel, CEO, Wellcome Trust/DBT India Alliance. “We are delighted to support the India Alliance in developing this proactive and much needed initiative. It reflects very well that Indian science has grown in volume and quality to such an extent that greater professionalization of research management is now needed to support it. We are pleased that the India Alliance is taking a lead on helping with this development.” Professor Mike Turner, Head of Infection and Immunobiology at The Wellcome Trust and Trustee at the India Alliance About the IRMI Pilot phase IRMI would initially be implemented as a pilot, with building capacity in grants administration at a few institutions. This would include mentorship, training, career development and networking opportunities for research managers and advice for the participating institution on its research management infrastructure. IRMI is expected to allow researchers more time to focus on their research instead of grants administration. The outcomes and feedback from the pilot phase would guide the future directions for IRMI.

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How to apply • Institutions wishing to be considered for participation in the IRMI pilot program should contact the Wellcome Trust/DBT India Alliance by filling out this form. • An authorized official (e.g. Director, Dean, Registrar, etc.) should apply on behalf of the Institution. • The decision of the India Alliance will be final. Role of host institution Host institutions would be expected, in future, to recruit research managers and develop their careers. An institutional contact should work with the IRMI team over the course of the pilot phase. What is included in the pilot phase The IRMI pilot phase would provide support with recruitment (if needed), mentoring and training of research managers in alignment with institutional aspirations and international best practice. Contact For further information, please contact IRMI@wellcomedbt.org

About the Research Management Consultant: Dr Savita Ayyar is a Research Management professional and Consultant with over ten years of experience in diverse areas of the field. She is the Founder of Jaquaranda Tree, a private consultancy service supporting organizations in India with capacity building for optimising research funding from diverse sources. Dr Ayyar initiated her career in Research Management at the Wellcome Trust in London, UK (2007-2010). She was formerly the Head of Research Development (2010-2017) at the National Centre for Biological Sciences, Bangalore, where she worked to initiate, implement and nurture the activities of the Research Development Office (RDO), a pioneer of its kind in India. Under her stewardship, operations at the NCBS RDO spanned grant management, philanthropic fundraising and endowments, intramural funding and News and Communications. She has significant experience as a mentor for science administrators, science communicators and other staff in research management roles. Dr Ayyar received her initial training in Biochemistry at the University of Delhi and Biotechnology at AIIMS, New Delhi. She completed her doctoral and post-doctoral work in Developmental Biology and Neurobiology, respectively at the University of Cambridge, UK.


OTHER ANNOUNCEMENTS

Please send your feedback, suggestions and contributions to public.engagement@wellcomedbt.org Follow us on www.wellcomedbt.org 24.


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