India Alliance Newsletter I Issue 11 I September 2016

News & Views Issue 10 Issue 11 July 2016 2016 September

News & Views Issue 10 July 2016

News & Views Issue 10 July 2016

INDIA ALLIANCE

EDITORIAL

Welcome to the September 2016 issue of the India Alliance Newsletter. In this issue we bring to you updates on India Alliance funded researchers, events, new research stories by our Fellows, general articles and interviews. We hope you find this an enjoyable and informative read.

At the outset, we would like to congratulate our Intermediate Fellow Dr Arun Shukla (IIT Kanpur) who recently received NASI-Young Scientist Platinum Jubilee Award in the field of Biomedical, Molecular Biology and Biotechnology by the National Academy of Sciences, India. As we mentioned in our last newsletter, India Alliance Fellows, Dr Shantanu Chowdhury (IGIB, New Delhi), Dr Abhik Saha (Presidency University, Kolkata), Dr Amit Dutt (ACTREC Mumbai), Dr Mahesh Kate (CMC Ludhiana) and Dr Rajiv Sarkar (CMC Vellore) along with the India Alliance CEO, Dr Shahid Jameel participated and represented the India Alliance at the first annual meeting of the DELTAS (Developing Excellence in Leadership, Training and Science) initiative in Nairobi on 5 and 6 July. The DELTAS initiative is managed by the Alliance for Accelerating Excellence in Science in Africa (AESA), and funded by the Wellcome Trust and Department of International Development (UK). This issue includes a short account of our Fellows’ experience at these meetings in Nairobi, Kenya. The India Alliance also participated at the recently held India-Africa Health Science Summit in New Delhi from 1-3 September. We will continue to bring updates on India Alliance’s efforts in fostering these India-Africa exchanges.

We are presently not accepting applications for any of our Fellowship schemes . The next call for applications will be announced for Clinical and Public Health Research Fellowships later this year/early January 2017. This issue features our new Early Career Fellows- Drs Sveta Chakrabarti, Preethi Badrinarayan and Paulomi Sangahvi.

The India Alliance continues to support various events aimed at increasing public awareness of science and important public health issues. Read about the public event in Shillong “Let’s talk Cancer in the North East” in this issue, which was held on 26 July in partnership with Indian Institute of Public Health, Shillong as part of our ongoing “Voices for Health” series. The next two public awareness events in this series will be on the topics of Environmental and Mental Health. More information on these programmes will be shared on our website shortly.

Our 14th biannual two-day Science Communication workshop will be held in Hyderabad on 26 and 27 2.

September. The next one-day SciComm and Career workshop in partnership with Nature India and Nature Jobs will be held at the XXXIV Annual Meeting of Indian Academy of Neuroscience on 18th October. This issue also includes information on the Science Communication competition, Famelab, that is being organized in India for the first time by the British Council.

In the Research Highlights section we bring to you the recently published work of Intermediate Fellow Dr Amit Dutt (Tata Memorial Centre - Advanced Centre for Treatment, Research and Education in Cancer, Mumbai) whose research provides novel therapeutic target for early stage tongue cancer. His group recently developed the first Indian germline database to catalog the variations in the genome of Indian population. Also find in this section, Intermediate Fellow, Dr Benu Brata Das (Indian Association for the Cultivation of Science, Kolkata) and his group’s recent work that provides a new rationale for cancer drug discovery involving cellular DNA repair machinery. Intermediate Fellow, Dr Guruprasad Medigeshi and his team based at Translational Health Science Institute, Faridabad, have identified new drugs for dengue virus from an existing pool of pharmacologically active drugs already approved for human use. This section also includes latest research stories of our Intermediate Fellows, Dr Mukund Thattai’s (NCBS, Bangalore) work on unravelling the evolution of eukaryotic cell’s transport system and Dr Dasaradhi Palakodeti’s (inStem, Bangalore) research on stem cell regulation, cancer and tissue regeneration in a flat worm model.

This issue also includes interviews of our Senior Fellow Dr Annapoorni Rangarajan, who is based at Indian Institute of Science, Bangalore and Dr Shivani Kanodia, Grants Adviser at the India Alliance.

As always, our heartfelt gratitude goes to all those who have contributed to this newsletter. Special thanks to Dr Amit Dutt for sharing an image for the cover of this issue, which is a schematic visual representation of different read outs from genomic sequencing.

We look forward to your valuable comments and suggestions for this newsletter.

Best wishes, Sarah Iqbal, PhD Public Engagement Officer

CONTENT

4 INDIA ALLIANCE FELLOWS New Early Career Fellows: Drs Sveta Chakrabarti, Preethi Badrinarayan and Paulomi Sanghavi

6 PUBLIC ENGAGEMENT CORNER Report on Public event : Let’s talk Cancer in the North East

9 SCIENCE COMMUNICATION Famelab, upcoming SciComm workshops

10 INDIA ALLIANCE RESEARCH HIGHLIGHTS Recently published works of Drs Amit Dutt, Benu Brata Das, Guruprasad Medigeshi, Mukund Thattai and Dasaradhi Palakodeti

14 INDIA ALLIANCE FELLOW IN SPOTLIGHT Dr Annapoorni Rangarajan, Senior Fellow, Indian Institute of Science, Bangalore

15 BRIDGING THE GAP BETWEEN INDIAN AND AFRICAN SCIENTISTS AND HEALTH SCIENCE RESEARCH

By Dr Shantanu Chowdhury, Dr Abhik Saha, Dr Amit Dutt, Dr Mahesh Kate and Dr Rajiv Sarkar

18 INDIA ALLIANCE STAFF CORNER Dr Shivani Kanodia, Grants Adviser, India Alliance

19 EXTERNAL ANNOUNCEMENTS Young Investigators’ meeting Chicago 2016,

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EARLY CAREER FELLOWS

New

INDIA ALLIANCE FELLOWS

Early Career Fellowship (basic research scheme) is a mentored Fellowship programme that provides a unique opportunity for postdoctoral researchers to carry out research in India towards building an independent research career. Applicants are expected to identify an important biomedical research question and design a project that would help answer this question. The proposal would also suggest how the proposed work would help develop the applicant's future independent research program. Submitted proposals are expected to be globally competitive. Applicants may set up long term training or collaborative laboratory visits (work outside Host Institution) for up to 24 months, anywhere in the world.

Next Call for Applications : May 2017 (tentatively).

Visit our website for more information on this Fellowship.

Uncovering the mechanisms of the systemic and gut immune response in Drosophila

This pathway plays important roles in both immunity and repair, where its dysfunction can lead to diseases such as blood cancers and severe compromised immunodeficiency.

Studies on the precise function of this pathway have been hampered due to its extreme complexity, which stems from multiple genes being involved at each step. We plan to use Drosophila as the model organism in our studies, as it has a simplified JAK/STAT pathway with a single receptor (Domeless), one Janus Kinase (JAK), and one STAT transcription factor, making this an ideal model to work mechanisms on how JAK/STAT signaling contributes towards wound healing, immunity and host survival.

Dr Sveta Chakrabarti Early Career Fellow 2016 Indian Institute of Science, Bangalore Website

Targeting kinase protein-protein interactions as cancer therapy

As a researcher in biology, I strive towards making an impact and on improving human health. After having successfully a very productive PhD in Life Sciences at the École Polytechnique Fédérale de Lausanne as well as a yearlong PostDoc, I am now excited to begin the next chapter of my career.

Dr Preethi Badrinarayan Early Career Fellow 2016 CSIR- Institute of Microbial Technology, Chandigarh

During the 4 years of my PhD studies in Switzerland, I brought a new topic of research to our group, i.e. stress signalling in model organisms. I worked on the cross talk of these stress pathways in context of immunity, which was the main focus of our group. My research showed for the first time that stress pathways, which usually contribute to enduring damage caused by infection, when excessively activated contribute to pathogenesis.

Website

Science has always been fascinating but I don’t know when it became a passion for me. The mystery associated with it and the joy of discovery are the main reasons that motivated me to seek a career in research. While a decent academic record with two gold medals; research support from DST, Fulbright and now Wellcome Trust/DBT India Alliance Fellowship along with the development of three new methods for drug discovery have encouraged me; the journal referees have left no stone unturned to keep me grounded. These experiences have laid the foundation for my formative years as a researcher and also enthused me to do better.

I have lived not only in Switzerland, but also in Austria and the United States of America. I think an international experience has given me a broad perspective to important issues of science in these two continents as well as in the developing world due to my Indian origins. Most importantly, I think my biggest training has been communicating my research in open days at EPFL, to a general audience as well as to other researchers outside my domain of expertise at many conferences.

Having majored in Microbiology, most of my pre-PhD work carried out in industry and academia was based on developing new enzyme immobilization techniques followed up with an advance diploma in bioinformatics at CSIR-Indian Institute of Chemical Technology (CSIR-IICT).

The major focus of my research is to investigate the influence of mutations on protein-protein interaction networks in oncogenic kinases in order to aid the development of targeted therapies for cancer. The motivation that led to defining this research problem was the curiosity instated during my PhD at CSIR-IICT to

I started as a Wellcome Trust/DBT Early Career Fellow in June 2016 at one of the most renowned institutes in India, the Indian Institute of Science. At IISc, I will be working on uncovering mechanisms of the systemic and gut immune response in Drosophila. In recent years, Drosophila melanogaster has emerged as a critical model system for deciphering molecular mechanisms on how signaling pathways respond to external stimuli. One such important pathway is the JAK/STAT pathway that is conserved from flies to mammals.

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EARLY CAREER FELLOWS

New

INDIA ALLIANCE FELLOWS

discover how the existing repertoire of kinase inhibitors with high efficacy can be honed to become more target specific. Thanks to my PhD supervisor, Dr G Narahari Sastry, who always supported my drive to work independently both during PhD and postdoctoral period. I am grateful to him for grooming me not only to conduct independent research but also for acquainting me with other areas affiliated with scientific pursuits.

Kinesin but also requires an opposite polarity motor, Dynein. This was when I got extremely interested in studying molecular motors, in particular the working of the Dynein motor deeply fascinated me.

The main reason for applying for the India Alliance fellowship, is the freedom that it gives to young researchers like me to explore our own ideas independently. My thrust has always been to integrate experiments with computation to solve my research problems. Use the data thus obtained to develop new methods and translate the findings from basic research into applications for societal good. I therefore approached Professor Susan Taylor, University of California San Diego; Dr. G. P. S. Raghava, CSIR-Institute of Microbial Technology; and Professor Holger Gohlke, University of Dusseldorf. While Professor Taylor is a world leader in kinase research who integrates both experiments and computations; Dr Raghava is an expert in bioinformatics and Professor Gohlke is the developer for AMBER. Thanks to the Wellcome Trust/DBT India Alliance fellowship, I have got an opportunity to get exposed to the rigours of method development as well as to an interdisciplinary way of kinase drug discovery. This is a lot more than what any young researcher like me would aspire for and with this experience the future independent research career is bound to have a logical direction and momentum.

Although cytoplasmic Dynein was discovered almost three decades ago, as compared to Kinesin the mechanism of Dynein function remains poorly understood. This has to do with its huge structure and its complex regulation pattern.

I gradually realized that in order to perform mechanistic. studies with these motors or any cellular process per se, one needs to complement in vivo biological approaches with some of the powerful physics based in vitro techniques. My postdoc in Dr. Roop’s Mallik lab at TIFR is the first step in that direction.

Dr. Mallik’s lab provides a highly favorable environment to closely study motor-based transport in an in vitro setting.

Here we extract latex bead phagosomes (LBPs) from Dictyostelium and study transport of these LBPs using optical trapping on in vitropolymerized microtubules.

Optical trapping is an extremely valuable technique. It provides tremendous information about various physical properties of motors (such as their force generation, velocity, processivity etc.), which is generally difficult to predict from other in vivo techniques. I strongly feel a combination of these biophysical measurements along with other biochemical techniques will provide a holistic view of the motor-based transport in the cell.

Investigating cellular transport proteins

My aim is to gain expertise in using these new techniques and acquire a skillset that is very different from what I have pursued. My long-term goal is to use this integrative approach to bridge the existing gaps in field of cellular biology and understand broadly how cellular transport occurs. Funding from Wellcome Trust/DBT India Alliance has definitely been a stepping-stone towards my goals. It has not only helped me become more independent but has also provided me an excellent platform to explore various avenues that are currently beyond my field of research

Dr Paulomi Sanghavi Early Career Fellow 2016 Tata Institute of Fundamental Research, Mumbai Website

I have always been interested in studying fundamental cellular processes that can be applied to most cell types. I believe that in order to cure a disease it is essential to first understand the normal mechanism by which the cell functions. My PhD research focused on studying the mechanism by which messenger RNAs are localized to specific cellular regions. We were interested in studying one such developmentally important mRNA, oskar, which localizes at the posterior region of the Drosophila oocyte.

Our lab mainly used Drosophila genetics along with other in vivo approaches to study this process. It was earlier shown that transport of oskar mRNA requires microtubules and microtubule plus end motor Kinesin. Surprisingly, our work showed that transport of this transcript not only requires

Presently we are not accepting applications for any Fellowship scheme. Our next competition will be announced later this year/early January 2017. Check our website for regular updates.

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PUBLIC ENGAGEMENT CORNER REPORT LET’S 26 JULY 2016

TALK CANCER IN THE NORTH EAST

India’s emergence as a fast growing economy and its consequential change in lifestyle-related behaviours are partially responsible for the country’s increasing cancer burden.

This disease is among the top leading causes of death among both rural and urban India. According to the latest National Cancer Registry Program, some of the highest incidence of cancer rates among men and women in the country were observed in Aizwal district in Mizoram and East Khasi district in Meghalaya.

The Wellcome Trust/DBT India Alliance and the Indian Institute of Public Health Shillong organised a public engagement event “Let’s Talk Cancer in the North East” on 26 July 2016 at the State Convention Centre, Shillong, to discuss the issue of cancer in the north east. This event is part of Voices for Health, an initiative that aims to celebrate biomedical research, discuss its impact and to create better understanding of public health issues in the country. The event assumed significance in light of growing incidence of cancer in India and particularly in the North East.

The discussion covered various aspects of the disease, ranging from risk factors for cancer, cancer diagnosis, disease management, socio-cultural behaviour towards cancer in the North East and more. The eminent panel included, Dr Preet Dhillon, epidemiologist at the Public Health Foundation of India, New Delhi, who started the discussion by giving an overview of cancer incidence in India, with particular focus on Meghalaya and the North East. The other panellists included prominent clinicians and academics from Shillong, Dr Judita Syiemlieh, oncologist at Civil Hospital Shillong, Prof (Dr) P Bhattacharya, Head, Department of Anesthesiology and Intensive Care at North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS)- Shillong, Dr Caleb Harris, Surgical Oncologist at NEIGRIHMS- Shillong and editor of Shillong Times, Ms Patricia Mukhim.

At the outset, Dr Dhillon alluded to the recent data from the ICMR Cancer Registry program when talking about the 1.5 million cancer cases every year in India and acknowledged that even though the registry programs such as these focussed on small population pockets in the states, they provided the best picture of cancer incidence in the country. It was very clear from

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the data that the North East and particularly Meghalaya had highest incidence of cancer, and also the highest proportion of tobacco-related cancers in the country (male 69.5%, female 45%). The data from the National Cancer Registry Program also showed that highest rates of tongue cancer and hypopharynx cancer in the world are in Meghalaya. Dr Dhillon opined that at least 15 years of data is required to be able to suggest conclusively how cancer rates are changing and suggested that investigations in North East should focus on the varieties of local tobacco and its consumption pattern, dietary habits, infections, genetic susceptibility, environmental exposure. In her address, leading cancer oncologist in Shillong, Dr Judita highlighted the need for building manpower in the health professions and promoting tobacco control more aggressively to tackle cancer effectively. Dr Caleb Harris, who recently moved to NEIGRIHMS, talked about the different cancer therapies. He informed the audience that at NEIGRIHMS, they have created a multidisciplinary team of cancer surgeons, radiologist, palliative care professionals, pathologist who discuss and decide the best possible treatment for different cancer cases that come to the hospital.

REPORT LET’S TALK CANCER IN THE NORTH EAST 26 JULY 2016

Organisers (IIPH Shillong and Wellcome Trust/DBT India Alliance) with the panelists

Dr Bhattacharya, who was instrumental in starting the first palliative care centre in Meghalaya NEIGRIHMS, stressed on the importance of emotional support for cancer patients. He was of the opinion that failure to cure cancer does not equal complete failure of the treatment and cancer treatment should always be accompanied by palliative care for the patient. Editor of the Shillong Times, Ms Patricia Mukhim, encouraged the audience, specially the younger health professionals and scientists, to write more about health for popular media. She called for more comprehensible science writing related to cancer and other diseases to be made available to the media to improve public understanding of diseases such as cancer which would lead to them making healthier lifestyle choices.

The event was attended by primarily young audience comprising of carers, doctors, academics, patients, students of social work, nursing, counselling and psychology and allied health, members of NGOs and the general public. The questions asked by the audience were on topics such as, cancer risk factors, cancer data collection methodologies,

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cancer screening and treatment, reasons behind high cancer rates in Khasi Hills and lack of seriousness about cancer prevention, effectiveness of cancer awareness programmes, family support for cancer patients, exposure to toxic radioactive substances and many others. Some serious issues were raised through this discussion concerning cancer awareness in the North East India, and tangible and useful solutions were offered by the panelists. At the event, Director of the newly formed IIPH Shillong, Dr Sandra Albert also announced that many such public programmes will be held in Shillong in the coming future. In addition to the discussion, informational material on cancer was available for the attendees. Members of the Palliative Care centre at NEIGRIHMS had set up a stall through which they shared information on the services provided by them. This event will hopefully act as a springboard for other public awareness programmes on cancer and other health issues in the North East.

Join "Voices for Health" here https://www.facebook.com/voicesforhealth/

REPORT LET’S TALK CANCER IN THE NORTH EAST 26 JULY 2016

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SCIENCE COMMUNICATION

Upcoming India Alliance Workshops One-day SciComm and Career workshop 18 October 2016

Two-day SciComm workshop 26-27 September 2016, Hyderabad Not accepting applications

XXXIV Annual Meeting of Indian Academy of Neurosciences NBRC, Manesar

For more details visit "SciComm Workshop" under "Quick Links" on our website 9.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

Novel therapeutic target for early stage tongue cancer

By Amit Dutt, Intermediate Fellow Tata Memorial Centre - Advanced Centre for Treatment, Research and Education in Cancer (TMC-ACTREC),Mumbai

Notch signaling pathway is a highly conserved cell signaling pathway present in most multicellular organisms. Mammals have four notch receptors, Notch1, Notch2, Notch3 and Notch4 which are present on the surface of the cell. Notch signalling pathway has a central role in cell to cell communication and has been shown to play a complex role in promoting stem cell maintenance, oncogenic or in inducing terminal differentiation in potential cancerinitiating cells; it acts as an oncogene in lymphocytes and mammary tissue or plays a growth-suppressive role in leukemia, liver, skin, and head and neck cancer. In our recent work, we present a novel clinical and functional significance of NOTCH1 alterations in early stage tongue cancer (tongue squamous cell carcinoma, TSCC).

Recent large-scale genome sequencing efforts of head and neck squamous cell carcinoma (HNSCC) have found inactivating NOTCH1 mutations in 10% to 15% tumors among Caucasian patients but no therapeutically relevant ‘oncogenic driver’ genes were identified. More recently, oral cancer studies among Chinese patients have revealed potential activating NOTCH1 mutations, suggesting somatic NOTCH1 mutations may reflect diversity of etiological complexity across ethnicities, with divergent role in oral cancer biology. Here, we describe Notch family members alterations across a sub set of oral cancer tumors: 68 early staged primary tongue squamous cell carcinoma samples (TSCC) of Indian patients by whole-exome, whole transcriptome sequencing, real-time PCR for copy number, along with transcript expression, and immuno-histochemical analysis.

Our results demonstrate that NOTCH1 harbors significantly lower inactivating mutations (~4%) compared to Caucasians (the Tumor Cancer Genome Atlas (TCGA) study) oral cancer data set, and that a considerable fraction of TSCC tumors (~37%) have upregulated Notch pathway that we show may be important in maintenance of stem cell component in

these tumors. Our study indicates inhibition of NOTCH activation by gamma secretase inhibitor or shRNA mediated knockdown of NOTCH1 inhibits spheroid forming capacity, transformation, survival and migration of the HNSCC cells suggesting an oncogenic role of NOTCH1 in tongue cancer.

This study has identified a sub group of tongue cancer patients that show hyperactivation of Notch signaling pathway. This unrestricted hyperactivation of Notch pathway causes dependency of these tumors on this pathway for its basic survival (“oncogenic addiction”). Given that Notch pathway activation can be blocked by a chemical compound, doing so can effectively kill the tumor cells in these patients in an exclusive manner while it would have no effect on other tongue cancer patients whose tumors do not harbor such molecular alterations and hence are not dependent on its function for its survival. In addition to identifying that a sub group of patients harbor Notch activation, this study further finds that these group of patients are largely non-smokers whose tumors have already spread to the lymph nodes. In brief, an early stage tongue cancer patient who is a nonsmoker and whose tumor has spread to lymph nodes are very likely to get benefitted with this discovery as Notch pathway inhibitors (already under clinical trial for other cancer types) are more likely to benefit them than other early tongue cancer patients.

Taken together, we present the first evidence for association of Notch pathway activation with tumors having spread to the lymph nodes and non-smoking status in early tongue cancer patients. We anticipate that these results could be the basis for therapeutic targeting of NOTCH1 in tongue cancer.

Notch pathway activation is essential for maintenance of stem-like cells in early tongue cancer Pawan Upadhyay,*, Sudhir Nair,*, Ekjot Kaur, Jyotirmoi Aich, Prachi Dani, Vidyalakshmi Sethunath, Nilesh Gardi, Pratik Chandrani, Mukul Godbole, Kavita Sonawane, Ratnam Prasad, Sadhana Kannan, Beamon Agarwal, Shubhada Kane, Sudeep Gupta, Shilpee Dutt, Amit Dutt. Oncotarget

First Indian germline database to catalog the variations in the genome of Indian population Cancer is a genetic disease caused by a sequential accumulation of mutations in the genome. Unlike normal cell genomes, a typical cancer cell genome harbors two kinds of variations: in addition to post birth acquired somatic mutations that are associated with the disease, it also contains germline variations, called as single nucleotide polymorphism (SNP),

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with frequency varying by ethnicity. Apropos, a crucial aspect of any tumor genome sequence analysis involves subtraction of such common SNPs that are also present in a normal cell of the same individual, followed by known SNPs present in the population, as reported in public databases such as dbSNP and 1000 Genomes Project.

INDIA ALLIANCE RESEARCH HIGHLIGHTS

The current built of dbSNP— the most comprehensive public SNP database—however, inadequately represents several non-European Caucasian populations, posing a limitation in cancer genomic analyses of data from these populations.

To fill this gap of Indian specific normal SNPdb, we present the first concerted effort to comprehensively identify and catalogue novel SNPs present exclusively in Indian population to generate a normal baseline reference database of SNPs present exclusively in Indian population, along with some caveats as detailed in the research manuscript. The TMC-SNPdb – Tata Memorial Center SNPdb-- is the first open source freely available, flexible and upgradable SNP database from whole exome data of 62 normal samples derived from cancer patients (hosted at ANNOVAR) from India origin. It consists of 114, 309 unique germline variants prevalent exclusively among Indian population at variant frequency. The TMC-SNPdb comes along with a companion subtraction tool that can be executed with command line option or using an easy-to-use graphical user interface (GUI) to deplete Indian population-specific SNPs, in addition to the dbSNP and 1000 Genomes Project.

Beyond cancer genome analyses, we anticipate universal utility of the TMC-SNPdb in several Mendelian germline diseases. Any researcher working on genome sequencing of any disease would wish for a normal germline SNP db from Indian population. More importantly, it comes along with a flexibility to allow researchers to add their own germline sequences to the TMC-SNPdb to filter Indian specific SNPs. This database has been incorporated in the dbSNP (the official database of all known SNPs in the world) and will be officially released with the next build of dbSNP release (build 149), scheduled for later this year. The TMC-SNPdb is also be available for immediate download from the ANNOVAR and our lab web page: http://www.actrec.gov.in/piwebpages/AmitDutt/TMCSNP/TMCSNPdp.html TMC-SNPdb: an Indian germline variant database derived from whole exome sequences Pawan Upadhyay, Nilesh Gardi, Sanket Desai, Bikram Sahoo, Ankita Singh, Trupti Togar, Prajish Iyer, Ratnam Prasad, Pratik Chandrani, Sudeep Gupta and Amit Dutt*

New rationale for cancer drug discovery involving cellular DNA repair machinery

By Dr Benu Brata Das, Intermediate Fellow Indian Association for the Cultivation of Science, Kolkata

“Synthetic lethality” or “Cancer specific cell killing” is the most exciting change in cancer treatment strategy since the invention of recent personalized chemotherapy. In this connection, Poly (ADP-ribose) polymerase (PARP) inhibitors have gained an immense interest in the clinical trial as a single agent for the treatment of breast and ovarian cancer due to mutations in the DNA repair genes like BRCA1 and BRCA2 or in combination with DNA topoisomerase 1 (Top1) inhibitors. FDA recently approved PARP inhibitors for ovarian cancer.

PARP is a family of 17 nuclear proteins involved in DNA repair and programmed cell death. One of the family members, PARP1, has been proposed to play a critical role in the early detection and repair of Top1cc-induced DNA breaks, a process known as PARylation. DNA topoisomerase 1, Top1, regulates DNA supercoiling both in the nucleus and mitochondria to enable faithful transmission of our genetic information to the offspring. However, Top1 is toxic when trapped on the DNA (Top1 cleavage complexes; Top1cc) in the presence of anticancer drug camptothecin (CPT) or endogenous DNA damage generated by reactive oxygen species (ROS). PARP1 catalyzes the addition of ADP-ribose polymers (PAR polymers) onto itself and Top1 and PARP inhibitors enhance the cytotoxicity of CPT in the clinical trials. Until the current study, PARP inhibitors were assumed to kill cancer cells by inhibiting the repair of Top1-induced DNA lesions. However, the molecular mechanism by which PARylation regulates Top1 nuclear dynamics is not fully understood.

In our recently published study we describe a novel role for PAR polymers on Top1 nuclear dynamics, which is

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independent from Top1-PARP1 interaction but dependent on PARP catalytic activity. We examine the effects of PARP inhibitors and/or in combination with CPT on fluorescently tagged-human Top1 subnuclear dynamics in living cells.

Using a combination of live cell microscopy and fluorescence recovery after photobleaching (FRAP) experiments, we establish that orally bioactive PARP inhibitors (Veliparib, ABT-888) efflux Top1 from the nucleolus to the nucleoplasm.

FRAP data reveals that combination of ABT-888 with CPT markedly increased the bound/immobile fraction of Top1 (Top1cc) across the nuclear genome compared to CPT alone, which is associated with increased cytotoxicity in the proliferating cells exposed to the combination of PARP inhibitor with Top1 inhibitor. In an unprecedented finding, we conclusively demonstrate that mutant Top1 (Top1N722S) is restricted to the nucleolus due to its deficiency in accumulation of CPT-induced Top1-PARylation and Top1cc formation.

The present study provides new mechanistic insights into the action of PARP inhibitors in combination with Top1 inhibitors relevant for cancer chemotherapy. PARylation of Top1 counteracts CPT-induced stabilization of Top1cc. Therefore ABT-888 markedly increased CPT-induced trapping of Top1 across the nuclear genome, which is coupled with increased cytotoxicity in cancer cells.

Poly(ADP-ribose) polymers regulate DNA topoisomerase I (Top1) nuclear dynamics and camptothecin sensitivity in living cells.Das, S.K., Rehman, I., Ghosh, A., Sengupta, S., Majumder, P., Jana, B and Das BB*. Nucleic. Acids Res., 2016 July

INDIA ALLIANCE RESEARCH HIGHLIGHTS

Drug repurposing: augmenting the drug discovery pipeline for dengue

By Dr Guruprasad Medigeshi, Intermediate Fellow Translational Health Science and Technology Institute, Faridabad WELLCOME IMAGES

As per the recent estimates, close to 60 million symptomatic dengue cases occur every year and the overall economic burden of dengue is nearly US$ 9 billion. Vaccine development efforts have resulted in the introduction of first ever dengue vaccine for human use in many countries and other promising vaccine candidates are in advanced stages of clinical trials. Nevertheless, there is lack of significant progress in antiviral development for dengue virus. A number of compounds have been identified as dengue inhibitors using in vitro and in silico approaches but no compounds have advanced to clinical trials in humans and proven to be effective. Repurposing drugs is one way of fast-tracking antiviral discovery as it builds on the pre-existing knowledge of the candidate drug. In cases where the drug has been proven to be safe for human use in other conditions, this process helps to bring the drug to human use faster than a new candidate drug, which, as per the industry estimates, takes 12-15 years from discovery to therapeutic use.

We screened the library of 1280 pharmacologically active compounds (LOPAC1280) for anti-dengue activity.

LOPAC1280 covers most major pharmacologically relevant target classes and many of them are approved as drugs for human use, thus providing an excellent platform for repurposing as antivirals. In our study, we used an imagingbased screening approach to screen LOPAC1280 for dengue inhibitors. We identified three inhibitors that specifically blocked early stages of dengue viral RNA replication. Our data suggest that treatment with the three dengue inhibitors, N-Desmethylclozapine, Fluoxetine and Salmeterol, leads to alteration in the autophagosome/lysosome biogenesis affecting early stages of DENV life-cycle. Our data further underscores the value and economic benefits of drug repositioning efforts that could be harnessed to augment the antiviral pipeline.

N-Desmethylclozapine, Fluoxetine and Salmeterol inhibit post-entry stages of dengue virus life-cycle.

Antimicrobial Agents and Chemotherapy. Medigeshi GR, Kumar R, Dhamija E, Agrawal T, Kar M. 2016. doi: 10.1128/aac.01367-16.

Evolution of the modern eukaryotic cell’s transport machinery Dr Mukund Thattai, Intermediate Fellow National Institute of Biological Sciences (NCBS), Bangalore

By Anusha Krishnan, Research Communications officer NCBS, Bangalore The inside of a present day plant or animal cell quite closely resembles a busy city. Like an urban metropolis with different districts interlinked by a traffic network, a cell has distinct compartments connected to each other by a dynamic transport system.

special selection mechanism.

Within cells, the Golgi complex is a set of compartments that is essential for processing, packaging and transporting proteins and other molecules. A key characteristic of the Golgi is its organisation as a ‘maturation chain’ with different compartments having variable molecular compositions.

These compartments perform different processing and packaging functions, especially in the synthesis and transport of giant proteins like collagen.

One set of such interlinked compartments – the Golgi complex – is essential for many cellular functions, and a question that has long puzzled scientists is: how did such a complex compartment and traffic system arise within a cell?

Scientists from the National Centre for Biological Sciences have a possible answer to this question through a mathematical approach to explore how such organisation could have evolved. Somya Mani and Mukund Thattai from the Simons Centre at NCBS have shown that the Golgi complex with its attendant traffic system can emerge spontaneously from a simple model with no need for a

The different compartments of the Golgi complex are connected to each other and to other cellular areas via mobile membrane-bound chambers called vesicles. Vesicles constantly bud off or fuse with compartments, forming a cell-wide transport system for different types of molecules.

In order to investigate the origins of the Golgi complex,

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INDIA ALLIANCE RESEARCH HIGHLIGHTS

Mani and Thattai simulated this traffic system. Built on broad and simple rules, they modelled the stream of vesicles budding out of source compartments and fusing with target compartments within a cell. These events were specified by budding and fusion matrices to create a collection of simulated cellular traffic networks that had settled into a state of equilibrium.

Now, Mani and Thattai did something unconventional – they filled up the budding and fusion matrices at random.

Therefore, budding and fusion events were random, with no specific purpose guiding these events.

But then, they got an astonishing result. In roughly 25% of their simulations, the researchers came across traffic networks that had developed distinct patterns closely resembling those of a Golgi complex. This means that despite the lack of a selection mechanism for budding or

fusion, a vesicular traffic network in a cell could give rise to a functional ‘maturation chain’ of compartments purely by chance.

In other words, Mani and Thattai’s work shows that the evolution of the Golgi complex is likely to have been nonadaptive – no selection system need have pushed cells to develop a Golgi complex.

The scientists are now planning to use their model to study infectious systems like tuberculosis and HIV, which are caused by intracellular parasites that hijack a cell’s vesicular traffic system for their own use.

Stacking the odds for Golgi cisternal maturation Somya Mani and Mukund Thattai. elife Read the original research story on the NCBS website

Study in flatworm model provide insights into stem cell regulation, cancer and tissue regeneration Dr Dasaradhi Palakodeti, Intermediate Fellow Institute for Stem Cell Biology and Regenerative Medicine, Bangalore

By Anusha Krishnan, Research Communications officer, NCBS, Bangalore Imagine trying to fly a kite without a tail. It swoops and loops and wiggles and finally crashes down into the ground. A kite without a tail is unstable, but add a tail at the right place, and your kite will fly steady.

Curiously, a similar connection between possessing a tail and being stable exists in molecules within living cells. Messenger molecules called mRNAs that convey instructions from DNA to protein factories for protein synthesis behave somewhat like kites. The messengers require a special tail to stabilise them so that they can function. Variability in the tail – in length or in their position, affects the function of the mRNAs, and hence influences gene expression.

Now, a team of scientists from the Institute for Stem Cell Biology and Regenerative Medicine (inStem) and the National Centre for Biological Sciences (NCBS) have found that many mRNAs – about 40% of the total – in the flatworm Schmidtea mediterranea have alternate forms that vary in the lengths and positions of their tails.

This study on S. mediterranea is the first of its kind in flatworm model systems, which, due to their incredible regeneration abilities, provide insights to stem cell regulation, cancer and tissue regeneration. This study could further our understanding of how varying mRNA tails could control gene expression in the context of regeneration.

In a typical cell, the expression of a gene encoding for a protein involves two major steps – the coding of a messenger RNA or mRNA from the genetic information in DNA, followed by the translation of the mRNA’s message into protein products at the cell’s protein factories. However, before translation, a process called ‘polyadenylation’ adds tails to mRNAs to stabilise these messengers and influence their function.

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The addition of these tails generally happens at specific sites – non-coding parts of mRNAs called 3’-untranslated regions or 3’-UTRs. However, through a phenomenon known as ‘alternative polyadenylation’, these tails can be added on to different sites on the mRNA, affecting its stability and therefore the amount or type of protein product formed.

The work has been a collaborative effort between Dasaradhi Palakodeti’s group at inStem and Aswin Seshasayee from NCBS. Apart from using a host of cutting-edge molecular techniques such as Next Generation Sequencing or NGS, the researchers also had to develop specific bioinformatics tools for analysing large amounts of genomic data.

The current study, which has focused on defining and characterizing a genome-wide database of the 3’- UTRs in S. mediterranea could be a very useful resource for researchers in this field. The tools and methods used in the work have been described in a publication in the journal G3:Genes|Genome|Genetics.

The authors of this paper believe that these tools and methods will lay the foundation for crucial breakthroughs in the flatworm model system and in our understanding of stem cell biology and the process of regeneration.

Genome-wide analysis of polyadenylation events in Schmidtea mediterranea. Vairavan Lakshmanan, Dhiru Bansal, Jahnavi Kulkarni, Deepak Poduval, Srikar Krishna, Vidyanand Sasidharan, Praveen Anand, Aswin Seshasayee,and Dasaradhi Palakodeti. G3. Genes I Genomes I Genetics Read the original research story on the NCBS website

INDIA ALLIANCE FELLOW IN SPOTLIGHT

DR ANNAPOORNI RANGARAJAN Senior Fellow, Indian Institute of Science, Bangalore

Dr Annapoorni Rangarajan is an Assistant Professor and Wellcome Trust/DBT India Alliance Senior Fellow based at the Indian Institute of Science, Bangalore. Her group is studying the molecular mechanisms that regulate self-renewal in normal and cancerous stem cells.

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

The major research focus of my laboratory is to investigate the molecular mechanisms that regulate the stemness of cancer cells. The sub-population of cancer stem cells are highly enriched in stemness and possess drug-resistance properties. Consequently, they are hard to kill with current therapeutic methods, and are suspected to be a major cause of cancer re-lapse. I believe that our findings have the potential to identify novel targets that can alleviate cancer stemness, thus aiding in making anti-cancer therapy more effective.

does not interfere with the other, has helped me find a balance. Saturdays are the ‘mummy-baby days’, when I try not to schedule a meeting or fiddle with emails while at home. Having satisfied one part of my brain, and without the feel of guilt for that part, I take my time out the next day (that is the Sunday!) for science and self. It is not the loss of one day, but the gain of the next day, fully rejuvenated, that seems to do the trick. Learning to say ‘no’ at times, even if it hurts my career growth, is another important thing that I practice.

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

I applied for India Alliance funding after five years of my career at IISc. By then, I had fully established my lab and a working system, trained a few students, and initiated clinical collaborations. Most importantly, we had obtained important scientific leads that needed pursuing. The India Alliance fellowship helped me test these hypotheses at the right phase of my career.

What keeps you going everyday?

From the success of trouble-shooting a small problem such as DNA/RNA prep to finding the missing link to a bigger scientific problem.

Annapoorni’s research group at IISc Bangalore

What inspired you to become a scientist?

To find out ‘how things work’. It started with the functioning of a ball-point pen and piecing together puzzles, and then got moulded while working on my Master’s dissertation topic on Judah Folkman’s early discoveries on angiogenesis – the quest for the unknown, the challenges en route, and the freedom to follow ones intuitions.

What challenges do you see for yourself as a woman scientist and how do you overcome them?

The biggest challenge I face is managing the demands of science and of my family, without feeling guilty of compromising one for the other. And amidst juggling between these two, finding time for myself! Keeping aside dedicated and compartmentalized time, where one chore

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Bringing together African and Indian Biomedical Researchers Dr Shahid Jameel, CEO Wellcome Trust/DBT India Alliance India and Africa have much in common – demography, disease burden and a predominantly young population.

Together, they support over a third of the world population and about half of its disease burden. With common problems, it makes sense to work towards common solutions.

The Wellcome Trust supports biomedical research at key international sites. The Wellcome Trust/DBT India Alliance, a co-funded partnership with the Department of Biotechnology (DBT), is one such example. In 2015, the Trust set up the Alliance for Accelerating Excellence in Science for Africa (AESA) with the African Academy of Sciences to build funding capacity, management and leadership in Africa. Its first initiative is called DELTAS (Developing Excellence in Leadership, Training and Science), which funds 11 groups across Africa to build leadership and capacity through human resource training and scientific research.

The collaboration between India Alliance and AESA started in November 2015 when two members of the AESA management team attended the India Alliance’s fellowship interviews and Annual Fellows Meeting. With a 6-year head start, India Alliance was seen as a model from which AESA could learn. The next step was to bring Fellows from the two programs together to establish scientific collaborations. This led to 5 India Alliance Fellows visiting Nairobi, Kenya in July 2016 for the DELTAS Africa Annual Grantees Meeting. The selection of India Alliance Fellows was based on their interest and the perceived research strengths on the African side.

Following this meeting, India Alliance Fellows also attended the Epidemiological Transition conference co-organised by the African Academy of Sciences (AAS) and Royal Society of Tropical Medicine and Hygiene (RSTMH).

proposed programs are translational in the truest sense, for example Afrique One –African Science Partnership for Intervention Research Excellence (ASPIRE) under the leadership of Dr Bassirou Bonfoh is conducting research on ecosystem of the pathogens, connecting humans, animals and environment together. This strategy will help us understand the need of co-habitation and not elimination as a target. Another example is IDeAL (the Initiative to Develop African Research Leaders) the program director Dr Sam Kinyanjui has pan life approach to theory of change involving students from schools, undergraduates and post graduates at various levels. Each program had a distinctive aim and approach to theory of change including bioinformatics, statistics, genomics, malaria eradication, tuberculosis/HIV infection, immunity and vocational excellence in research.

While all eleven programs are making great strides and forging ahead, they have met with fair share of hurdles, including administrative standoffs from institution or local government, lack of interest among the students and challenging work environment for the clinicians where research time is non-existent. Despite that the abstracts presented during the conference were high quality and practice changing. The most spoken and unspoken word throughout the conference was research integrity, which was truly reflected in the work presented in the abstracts.

India Alliance Fellow Dr Mahesh Kate (R) with Dr Bassirou Bonfoh (L) of Afrique One –ASPIRE

How did these meeting turn out from the Fellows’ perspective? Read on.

The Wellcome Trust has now set up an Advisory Group for Research Ecosystems in Africa and Asia. This group, which also includes the Director of AESA and the CEO of India Alliance, will chart out possible ways for DELTAS and India Alliance Fellows to collaborate, learn from each other and help build capacity on both sides.

--------Dr Mahesh Kate, Intermediate Fellow CMC Ludhiana Considering the immeasurable health and environmental challenges confronted by humans daily, collaboration among scientists is crucial. Furthermore, given the global nature of health problems a synergistic international diversity in collaboration may be real game changer. This opportunity to bridge health science across two continents was provided by the Wellcome Trust/DBT India Alliance and the African Academy of Sciences (AAS).

The DELTAS Africa is a unique five-year program, wherein 11 musketeers’ (read leading Scientists) will develop 1300 independent researchers in sub-Saharan Africa. The

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Following the DELTAS meeting, the conference on epidemiological transition was of acute interest to me. India and Africa are passing through a phase wherein the communicable diseases are reducing in number at the same time non-communicable diseases (NCDs) are increasing exponentially. What we are seeing uniquely in India-Africa, as we are passing through this phase is an interaction between communicable diseases and NCDs. We are seeing strokes in patients with tuberculosis, HIV, brucellosis, malaria, varicella zoster and invasive fungal infections. At the conference, it was emphasized that research focus on NCDs is vital for the future of a healthy society. However, we need solutions, which are sustainable and inclusive. Another interesting epidemiological transition noted is the occurrence of late age schistosomiasis, a devastating parasitic infestations, due to better childhood treatment. So the community has to be aware of the changing faces of these health challenges. Dr Dixon Chibanda of the University of Zimbabwe, in his keynote address drew the attention towards mental health issues. He highlighted the need of integration of mental health care in existing systems. However, the emphasis of his talk was on efficacy of non-pharmacological measures like community interaction to reduce the severity of depression.

Bringing together African and Indian Biomedical Researchers The India Alliance contingent was a diverse bunch, with a hookworm epidemiologist, lung cancer biologist, genomics expert, stroke clinician scientist and viral biologist- a perfect concoction, which brewed well for four days. We all took part in an innovative leadership forum during the conference.

Leader of our India Alliance contingent, Dr Shahid Jameel mentioned a very interesting aspect of a leader, generosity, citing a story between eminent Indian aerospace engineer Prof Satish Dhawan and former ISRO secretary and President of India, late Dr APJ Abdul Kalam. Prof Dhawan took the blame of the first launch failure of ROHINI satellite as a chairman but after a year when it was successfully launched he asked APJ Abdul Kalam to conduct the press conference, encouraging the young researcher to continue his pursuit in scientific research, which is otherwise riddled with mines of disappointment.

established and the budding African scientists was the commonalities between us – not only do we have similar disease profile, our research and workplace challenges too are very similar! Such a degree of overlap presents us with the opportunity to synergise our interests and expertise, and work together in multi-centric studies to address problems common to both places. While this is intuitively appealing, developing long-term, mutually-beneficial partnerships will require more interactions between Indian and African scientists. Holding joint India Alliance and DELTAS meetings at regular intervals could provide such a platform.

Encouraging scientific exchange through short and longterm travel grants and fellowships to researchers at all career trajectories can also go a long way in promoting research interactions, thereby creating opportunities for mutuallybeneficial research collaborations.

During the meeting we could meet with many international funding agencies such as, National Institute of Health, USA that has the H3 Africa initiative; Grand challenges Africa; Medical Research Council, UK; UK Department for International Development; Institut Pasteur, France and World Health Organization. The most interesting part was that funding is available for good research irrespective of the approach one takes to tackle human health problems. Grand Challenges Africa and MRC UK suggested I apply to them with my research project of preventing stroke in patients with tubercular meningitis, which may help approximately 1 million patients worldwide each year.

The India-Africa meeting with the DELTAS and AAS has brought us closer. The India Alliance has also offered African scientists to compete for their Fellowship schemes, thus throwing a door wide open for synergistic international collaborations. Kudos to the India Alliance, the Wellcome Trust and the African Academy of Sciences for this initiative.

One of the side meetings between India Alliance and DELTAS fellows (Photo credit: Abhik Saha)

Dr Abhik Saha, Intermediate Fellow Presidency University Kolkata One of the main reasons to apply to attend this meeting was because my lab works on tumor viruses – particularly EBV, the first human tumor virus identified from the Equatorial Africa Region – specifically Uganda. A number of virus mediated diseases resulted in some of the most challenging disease pandemics in human history particularly in Africa continent – such as, Human Immunodeficiency virus (HIV)/AIDS in Sub-Saharan Africa and recent outbreak of Ebola virus in West Africa. Even now, HIV-infections and its related diseases represent as one of the major public health concern throughout Africa. HIV infection leads to propagation of a number of communicable diseases triggered by tuberculosis (TB), Malaria and several viral infections. Tumor viruses’ infections increase the incidence of developing multiple cancers – both of lymphoid and epithelial in origin. The most prevalent cancers in HIVinfected populations are KSHV-associated Kaposi’s sarcoma (KS) in males and HPV associated cervical cancers in females.

In childhood cancers, Burkitt’s lymphoma is the most prevalent in children between the ages of five and nine. This raises the urgency of understanding the underlying mechanisms that govern viral disease emergence and subsequent cancer development in African populations. On a different note, the emergence of viral infection can also be understood by the mandate that every ‘traveler’ requires proper vaccinations against “Yellow Fever” and “Polio” – both are virus originated. These health scenarios perfectly align with my research interests and the opportunity to network at the Annual meeting will be useful for future collaborative engagements between India Alliance and the DELTAS on these similar disease landscapes.

The India Alliance contingent at the meetings: (L-R) Dr Shahid Jameel, Dr Rajiv Sarkar, Dr Mahesh Kate, Dr Amit Dutt, Dr Shantanu Chowdhury, Dr Abhik Saha (Photo credit: Shantanu Chowdhury)

Finding common grounds with African scientists Dr Rajiv Sarkar, Early Career Fellow CMC Vellore I was keen to utilise the opportunity to attend the DELTAS and RSTMH meetings to learn more about the biomedical research landscape in Africa and to establish research network with African scientists working on infectious diseases.

What was striking from my interactions with both the

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Bringing together African and Indian Biomedical Researchers keen to understand the diversity of somatic alterations in the back drop of germline diversity underlying different ethnicities. I sincerely hope there would be some follow up interactions leading to actual scientific collaboration with these few selected researchers.

Learnings from the meeting Dr Shantanu Chowdhury, Senior Fellow CSIR-IGIB, New Delhi It was a good learning experience to get a glimpse of African science and administration and I thank Indian Alliance for making this possible. A big take-home for me was the large scale planning that has been done to structure the DELTAS programs, spanning across mostly infectious disease management and modes of assessing its impact on healthcare.

The India Alliance team with Dr Thomas Kariuki, Director, AESA (Photo credit: Dr Abhik Saha)

Fostering India-Africa lab exchanges

Apart from the administrative structure laid out for each project, it was evident that there was dedicated expertise available to not only guide each program but also to gauge how each program was doing as it progressed. In addition, a program that made me think highly of the overall DELTAS arrangement and planning was their foresight to design something called 'theory of change'. From what I could understand, this was to learn and change as they move with individual programs and bring forth required changes from continuous engagement with program directors.

Dr Amit Dutt, Intermediate Fellow ACTREC, Mumbai Familiarity with the plural nature of the various research groups actively involved in research and direct interaction with them are the two essential criteria to foster organic collaboration. This trip to Nairobi was successful in fulfilling both these basic ingredients. To begin with, my familiarity with the research landscape in African countries started with learning several acronyms that otherwise I would have not come across, such as DELTAS Africa initiative; the AAS, AMARI; CARTA+; MECAD; WACCBIP , etc— of which, I found WACCBIP (West African Centre for Cell Biology of Infectious Pathogens) overlapping with my research interest. In general, I found most of the researchers presenting their work as pretty thorough in their work which speaks a lot about their sincerity and depth of their scientific temperament and dedication, despite limited resources. I also got a chance to interact with a few enthusiastic researchers who expressed their keen interest to get trained in my laboratory for making biological sense of high throughput data and their functional follow up.

Some clinicians expressed interest to collaborate for profiling EGFR and KRAS mutations in lung cancer patients of African (Kenyan) ethnicity. I found these initiatives very encouraging with mutual interest as I am personally very

Another important point that made an impression on me was the discussion surrounding science uptake - in general, this would mean how scientific output (laboratory or first level of evidence so to say) is taken to the next step. Here, discussion was justly on policy level changes given that most programs involved infectious disease management issues. In a broader sense, this could apply to any science project/proposal where defined goals are achieved. And then the next step could be technology transfer, healthcare diagnostics/management or policy. I realize this is different from the current India Alliance program where focus rightly is more on individual excellence. It is possible that this experience will be of benefit to us when we think of multiinvestigator programs in future with focus on healthcare impact in a pan-India sense.

Why India and Africa need aligned health research strategies Similar demographics and disease burden, and a visible shift from communicable to non-communicable diseases in both India and Africa present a strong case for ramping up south-south collaborations in health research, argue Shahid Jameel (CEO, Wellcome Trust/DBT India Alliance), Tom Kariuki (Director, Alliance for Accelerating Excellence in Science in Africa, Nairobi, Kenya) and Simon Kay (Head, International Operations and Partnerships, Wellcome Trust, London, UK).

Read the full article on Nature India website

Outwards to Africa With India aspiring to be a ‘knowledge economy’ and a global power, it must also use health research and innovation to improve people’s lives at home and overseas. Some key partnerships to build capacity, support health research and promote innovation have developed between international funders and either Africa or India. These African and Indian programmes should learn from each other and together build sustainable science-based partnerships. A useful trend with international funders now is to recognise the value of local decision-making and management. This will positively impact the partnerships writes Dr Shahid Jameel in the Hindu Read the full article in the Hindu

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INDIA ALLIANCE STAFF CORNER

DR SHIVANI KANODIA, Grants Adviser

Dr Shivani Kanodia joined the India Alliance grants team in September 2014 after finishing her PhD at ICGEB, New Delhi .

When not busy reviewing applications and advising Fellowship applicants, Shivani works on keeping her photographic and poetic interests alive.

What is your background?

I am a pakka “Dilliwali” (a true-blue Delhi-ite). I was born and brought up here and pursued BSc. (Biochemistry) from University of Delhi. After completing Masters in Biotechnology from School of Biotechnology , Jawaharlal Nehru University I joined International Centre for Genetic Engineering and Biotechnology, New Delhi for PhD. After a five year stint with the malaria parasite P.falciparum I joined India Alliance in September 2014. Despite being in Delhi throughout, work has taken me across the globe to attend various courses, meetings and conferences. A cell biology course at Hong Kong and a 15 day visit across Germany as a part of delegation representing India at The Lindau Nobel Laureate Meetings were perks of being a PhD student. My tenure as a Fulbright Fellow at Harvard School of Public Health, Boston was an enriching and a life changing experience from me. During this visit I got a chance to meet people from various academic streams from across the world. My interaction with people involved in science administration and policy influenced my decision to change gears and enter science administration.

Isolated from Mosquitoes”. I was once again in awe of nature after reading about this work. It talks about how various components of a virus need to get together to infect a mosquito. It describes Guaico Culex Virus, a multicomponent RNA virus isolated from mosquitoes which comprises five segments, each of which is packaged separately. The mosquito has to get infected by at least four out of five particles to acquire the infection. I have heard people in the field talking about multiple viruses infecting same cell for productive infection. Here, in this article nature shows us that it has thought of this already.

How has your India Alliance journey been so far?

Joining India Alliance was a conscious choice to move away from lab research to science administration. Seeing colleagues from various fields in science, transitioning smoothly to administration has been inspiring. It’s an entirely different experience but ground rules (passion and dedication for work) remain the same. We face several challenges while attempting to maintain excellence but an amicable team makes working at the India Alliance enjoyable. Healthy work environment and smiling faces at the office makes it a place to be. To sum it up, time spent at India Alliance has been Inspirational and Adventurous.

What book are you reading right now?

I have just finished reading “The Fault in our stars” by John Green. It’s a heartbreaking tale of terminally ill cancer patients Hazel and Augustus filled with hope, love and humor. Next on the list are some wordless picture books which I will be reviewing for a friend’s blog.

What was the last piece of research that excited you?

I have not been reading a lot of research articles of late (I can talk about a lot of children books though). A recent piece that comes to my mind is “A Multicomponent Animal Virus

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

Apart from reading and writing poetry, which takes a back seat off and on, my relationship with Nature has been quite consistent. A significant amount of my time is spent conversing with the chirping birds and the fluttering trees.

Cloud watching is one of my favorite activities. Nowadays, most of my time is spent with my 11 month old daughter “Aryah”. We read, enjoy rhymes, and go for nature walks. I love capturing these moments with my camera.

Who inspires you (living or dead)?

My father is my biggest inspiration He had faith in me at every turn, He taught me to stand for right And to fight for justice with all my might, His unshaken faith has sailed me through To take decisions about which I had no clue, He has always motivated me to go where we find happiness Be it ICGEB, India Alliance or somewhere else!!

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