India Alliance Newsletter I Issue 13 I January 2017

News & Views

EDITORIAL

Best wishes for the New Year from all of us at the India Alliance.

In the first issue of 2017 we bring to you updates on our Fellowships and events, new research stories penned by our Fellows themselves, new funding opportunities and interviews.

We hope you find this issue an engaging and informative read.

We are presently accepting applications for Senior and Intermediate Fellowships in Biomedical Research and Clinical and Public Health Research Fellowship schemes. More information on these Fellowships is included in this issue. This newsletter also features new India Alliance Fellows and the research they are pursuing.

In the Research Highlights section we feature research stories by our Fellows. Intermediate Fellow, Dr Nitin Gupta’s (IIT Kanpur) recently published work in Nature Communications which will further enable us to decode information processing in the brain. Dr Soumen Basak, Intermediate Fellow at National Institute of Immunology, Delhi, and his group’s latest research further elucidates the complex regulation of inflammatory immune response in macrophages. Dr Amit Awasthi (Intermediate Fellow, THSTI Faridabad) and his collaborators show protective effects of dietary potassium in bowel disease in their latest research published in Frontiers in Immunology. Dr Rashna Bhandari in collaboration with IA Fellow, Dr Roop Mallik, published their work in Biochemical Journal which provides novel insights into the role of molecular messengers, Inositol Pyrophosphates, in regulating cellular traffic. Dr Amit Dutt and his colleagues at ACTREC, Mumbai provide the first comprehensive description of druggable mutation spectrum in lung cancer patients in India. The research highlight section also features the research story of our Senior Fellow Dr Raghu Padinjat, in which he and his team provide new links between endocytosis and cell membrane recycling. This newsletter includes interviews of our Senior Fellow Dr Vikram Mathews, Christian Medical College, Vellore and India Alliance Programmes Manager Dr Srikrishna Sulgodu Ramachandra.

The India Alliance “Event Support” has been replaced by our new funding scheme for interdisciplinary meetings-the “India I EMBO Symposia” is a joint collaboration between the India Alliance and European Molecular Biology Organization (EMBO) which aims to support up to three meetings that will address discovery and innovation through an interdisciplinary approach, with the speakers and participants discussing important global challenges in the context of the life sciences.. More information on this funding opportunity is included in this issue and on the India I EMBO Symposia website. In an effort to inform Indian researchers abroad about science career landscape in India, India Alliance has supported various Young Investigator meetings (YIMs) in India and outside. One such YIM was held in Chicago (21-23 October 2016) for the first time, a report of

which is included in this issue. Our Intermediate Fellow Dr Smarajit Polley at the Bose institute, Kolkata, which hosted the 19th Transcription Assembly Meeting 2016, writes about this meeting and the road ahead for such exchanges on transcription and RNA biology in India. Intermediate Fellow, Dr Nitin Gupta and his colleagues at IIT Kanpur conducted the 3rd Annual BSBE Winter Workshop, 2016 (Neural Systems: from circuits to behaviour) on 17-18 December 2016. In this issue he gives us a brief glimpse into what took place at this workshop.

Both of these meetings were partly supported by the India Alliance.

The India Alliance continues to organise and lend its support to various Science Communication training activities. Our 3rd oneday SciComm and Career workshop in partnership with Nature India and Nature Jobs was held at the 15th All India Cell Biology Conference & International Symposium on Functional Genomics and Epigenomics at Jiwaji University, Gwalior on 16 November 2016 which was followed by our 18th SciComm101 workshop at SASTRA University, Thanjavur. The India Alliance also supported Science Communication competition, FameLab, which was brought to India for the very first time by the British Council India and Cheltenham Festival, UK. This issue includes brief reports on all these workshops.

As part of the ongoing “Voices for Health” public engagement series, India Alliance in partnership with Centre for Environmental Health, Public Health Foundation of India, organized a public awareness event around air pollution in Delhi on 13 December. This event was preceded by Environmental Health sensitization workshops at schools and undergraduate colleges with our partners, PHFI and Happy Hands Foundation. Read about this half-day public event in this issue.

As always, we really appreciate and value the contributions for this Newsletter. Special thank you to our Intermediate Fellow, Dr Nitin Gupta (IIT Kanpur) for the cover image, which is a high resolution microscopy image showing the dye-filled bundle of neurons (Kenyon cells) in the olfactory centre, also known as the mushroom body, of the insect brain. The different colours indicate depth.

Here's to another year of new beginnings, endless possibilities, growth and exciting explorations. We continue to look forward to your valuable comments and suggestions.

Best wishes, Sarah Iqbal, PhD Public Engagement Officer, Wellcome Trust/DBT India Alliance

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CONTENT

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CALL FOR APPLICATIONS

Senior and Intermediate Fellowships in Basic Biomedical Research Clinical and Public Health Research Fellowships

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New INDIA ALLIANCE FELLOWS Drs Akhilesh Pandey (Margdarshi Fellow), Srivatsan Seergazhi Gopalan (Senior Fellow), Mohan Joshi, Siddhesh S Kamat, Satish Khurana, Sonam Mehrotra (Intermediate Fellows), Aditi Maulik, Pinky Kain, Deepak Y Kamath (Early Career Fellows), Urvita Bhatia (Research Training Fellow)

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INDIA ALLIANCE FELLOW IN SPOTLIGHT Interview with Dr Vikram Mathews, Senior Fellow, Christian Medical College, Vellore

12 INDIA ALLIANCE FELLOWS’ RESEARCH HIGHLIGHTS Recently published works of Drs Rashna Bhandari, Raghu Padinjat, Soumen Basak, Amit Dutt, Amit Awasthi, Nitin Gupta

16 INDIA ALLIANCE EVENT SUPPORT Call for Applications- India I EMBO Symposia Reports of Young Investigator Meeting-Chicago, 19th Transcription Assembly Meeting 2016 3rd Annual BSBE Winter Workshop, 2016 (Neural Systems: from circuits to behaviour)

20 INDIA ALLIANCE SCIENCE COMMUNICATION 3rd SciComm & Career Workshop, FameLab Workshop-SciComm Workshops, 18th SciComm101 Workshop

21 INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER Public engagement events in ‘Voices for Health’ series - #OurEnvironmentOurHealth

22 INDIA ALLIANCE STAFF CORNER Dr Srikrishna Sulgodu Ramachandra, Programme Manager, India Alliance

23 EXTERNAL EVENTS Conference on Conservation Science and Sustainable Development at ATREE, Bangalore

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CALL FOR APPLICATIONS Senior and Intermediate Fellowships in Biomedical Research Preliminary application deadline 7 February 2017

The Wellcome Trust/DBT India Alliance invites applications for its Senior and Intermediate Fellowship scheme. These 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 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 advice 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 715 years of post-PhD research experience.

Intermediate Fellowship: For postdoctoral researchers who have been successful in building a track record of pursuing a cutting edge 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 forms are available on the India Alliance online application System (IASys) Please visit our website for further information on these Fellowships.

Write to us with queries to info@wellcomedbt.org *We encourage Clinicians and Public Health researchers to apply in a separate competition (see page 5).

RECENTLY RECOMMENDED AWARDEES Intermediate Fellowships (November 2016 round)

Senior Fellowships (November 2016 round)

Dr Aswin Sai Narain Seshasayee, National Centre for Biological Sciences, Bangalore Dr Harsha Gowda, Institute of Bioinformatics, Bangalore Professor Jaladhar Neelavalli, *Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram Dr Amit Kumar, *CSIR-Indian Institute of Toxicology Research, Lucknow Dr Rohit Anthony Sinha, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow Dr Ajaz Ul H Wani, *University of Kashmir, Srinagar Dr Sona Rajakumari, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram Dr Sanjeev Shukla, Indian Institute of Science Education and Research, Bhopal Dr Geeta Ram, All India Institute of Medical Sciences, New Delhi Dr Senthilkumari Srinivasan, *Aravind Medical Research Foundation, Madurai

Dr Rishikesh Narayanan, Indian Institute of Science, Bangalore Dr Thomas J Pucadyil, Indian Institute of Science Education and Research, Pune Dr Amit Singh, Indian Institute of Science, Bangalore Dr Uma Ramakrishnan, National Centre for Biological Sciences, Bangalore Dr Subba Reddy Maddika, Centre for DNA Fingerprinting and Diagnostics, Hyderabad

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

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CALL FOR APPLICATIONS Clinical and Public Health Research Fellowships Preliminary Application deadline 9 February 2017

The Wellcome Trust/DBT India Alliance invites applications for three Fellowship schemes: Early Career Fellowships, Intermediate Fellowships and Senior Fellowships.

Eligibility 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 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.

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 715 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 Essentials on the application: • A research proposal that 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 salaried position or commitment to a salaried position at the Host Institution is not required.

• A Sponsor at the Host Institution, who can guarantee space and resources for the duration of the award.

• In case of an Early Career Fellowship, a Fellowship Supervisor, who can guarantee access to laboratory space and resources required for the project as well as provide relevant scientific guidance for the tenure of the Fellowship.

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

RECENTLY RECOMMENDED AWARDEES Early Career Fellowships

Ms Madhumitha Balaji, Sangath, Porvorim

Dr Suparna Ghosh-Jerath, Public Health Foundation of India, Delhi Dr Janardhanan Narayanaswamy, National Institute of Mental Health and Neurosciences, Bangalore

Intermediate Fellowships

Senior Fellowships

Dr Prashanth Nuggehalli Srinivas, *Institute of Public Health, Bangalore Dr Rishikesh Behere, *KEM Hospital and Research Centre, Pune Dr Nivethida Thirugnanasambandam, National Institute of Mental Health and Neurosciences, Bangalore Dr Benedict Weobong, Sangath, Porvorim Dr Anita Nath, Public Health Foundation of India, IIPH-H, Bangalore campus, Bangalore Dr Devaki Nambiar, Public Health Foundation of India, Delhi

Dr Venkatesan Chakrapani, Postgraduate Institute of Medical Education and Research, Chandigarh Dr Ghattu Vedamurthy Krishnaveni, CSI Holdsworth Memorial Hospital, Mysore

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

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INDIA ALLIANCE FELLOWS

Dr Akhilesh Pandey Margdarshi Fellow 2015

National Institute of Mental Health and Neuro Sciences (NIMHANS) and Kidwai Memorial Institute of Oncology, Bangalore WEBSITE

Establishing a Center for Molecular Medicine The Wellcome Trust/DBT India Alliance Margdarshi fellowship will allow me to combine biology and medicine to address clinical problems in a holistic fashion and I am excited about translating our discoveries into clinically useful diagnostics, biomarkers and therapeutics. My goal is to establish a Center for Molecular Medicine to accelerate biomedical research and translation in a clinical setting. This core of this center will be a multi-disciplinary scientific team that will leverage the outstanding clinical resources and capabilities of NIMHANS and Kidwai Memorial Institute of Oncology to initiate research programs using a systems biology approach. Several sophisticated technology platforms - next generation sequencing, genome editing, mass spectrometry and bioinformatics – will be employed to drive the research that will be centered on the following themes: Cancer and personalized medicine We will characterize glioblastoma and gastric adenocarcinoma using genomic (exome sequencing) and proteomic approaches. We will generate cellular and animal models of these tumors and use them to identify activated signaling pathways and to test pharmacological inhibitors. We will also develop assays for detecting mutant cell free DNA in blood.

Cancer signaling We will develop a platform for using CRISPR/Cas9-based genome editing to generate isogenic cells expressing potential oncogenic drivers for systematic analysis of such mutations.

Protein Biomarkers

i) Parkinson’s disease: Parkinson’s disease is a neurodegenerative disorder for which there are currently no clear diagnostic or prognostic biomarkers for clinical use. We will apply mass spectrometry-based discovery and targeted validation approaches to identify novel biomarker candidates. ii) Traumatic brain injury: Traumatic brain injury (TBI) is a major cause of morbidity in vehicular accidents, contact sports and in military personnel.

The consequences of mild TBI include somatic, cognitive and behavioral symptoms whose biological underpinnings remain poorly understood. We will carry out mass spectrometry-based discovery experiments to identify potential biomarkers for TBI.

Figure description: Characterization of glioblastomas using genomic and proteomic approaches. The tumor exomes will be sequenced and the putative driver mutations will be monitored in the blood of patients. CRISPR/Cas9 based gene editing will be used to insert the identified driver mutations into normal cells to generate isogenic cellular models. These cells will be monitored for changes in their phenotypes induced by the driver mutations. The tumor tissue and cells engineered to contain potential driver mutations will be propagated in mice to study activated signaling pathways and test efficacy of drugs.

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Innovative Nucleoside Probes as Multifunctional Toolbox to Study RNA Structure, Dynamics and Function Dr Srivatsan Seergazhi Gopalan Senior Fellow 2015 Indian Institute of Science Education and Research (IISER), Pune

DNA and this process is conserved in all organisms, thereby playing an important role in genomic maintenance during repair of DNA double strand breaks and reactivation of stalled DNA replication fork. However, HR can also cause genomic instability via gene conversion, crossing over and mutation incorporation (under stress), thereby resulting in various genetic modifications. Therefore, HR plays a pivotal role in maintaining the equilibrium between genomic integrity and genetic diversity. Although HR is an extensively studied process, it remains unclear how this equilibrium is regulated during DNA repair. Recent data including our own suggested that, during cell division, chromosome cohesion is an evolutionary conserved process and bacteria may also utilize a cohesion-dependent mechanism for DNA double strand repair. Therefore, our work will utilize E. coli as a model to understand this process as it provides a highly tractable and mutable model to test the role of cohesion in HR dependent DNA double strand repair.

Investigating connections between lipid signaling networks and human diseases

WEBSITE Genome-wide computational analysis has revealed the presence of several putative G-quadruplex (GQ) forming sequences in the telomeric repeats, promoter DNA regions and untranslated regions (UTRs) of messenger RNA. Biochemical and biophysical investigations suggest that such sequences may play critical roles in chromosome maintenance and regulation of proliferation-associated genes. In terms of structure, G-rich sequences adopt a variety of folding topologies in vitro, which depend on the sequence and ionic conditions. Although the formation of GQ structures in mammalian cells has been documented recently, it is not clear what topology a G-rich sequence adopts inside the cell and which structure is responsible for its function.

In this context, moving away from the traditional approach of “one label-one technique”, we have employed an innovative approach to investigate the GQ structure and function in cell-free and cellular systems by using conformation-sensitive multifunctional nucleoside analogue probes. We have developed novel minimally perturbing nucleoside analogues equipped with hybrid labels, which would enable the concurrent analysis of GQs in real-time and 3D by fluorescence, NMR and X-ray crystallography techniques. These studies would not only accelerate the discovery of new diagnostic tools and therapeutic strategies, but also would significantly advance our fundamental understanding of nucleic acid structure and function.

Dr Siddhesh S. Kamat Intermediate Fellow 2015 Indian Institute of Science Education and Research (IISER), Pune WEBSITE

Chromosome cohesion in Homologous Recombinationdependent DNA double strand repair Dr Mohan C Joshi Intermediate Fellow 2015 Jamia Millia Islamia, New Delhi

WEBSITE Homologous Recombination (HR) is the major reason for the spread of antibiotic-resistant genes in pathogenic microbes. HR involves nucleotide exchange between two similar or identical molecules of

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PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, cataract) is a rare genetic neurological disorder in humans caused by deleterious mutations to the Abhd12 gene. The Abhd12 gene codes for the serine hydrolase (SH) ABHD12, which serves as the principal lysophosphatidylserine (lyso-PS) lipase enzyme in the mammalian brain, thereby terminating lyso-PS signaling. We recently discovered another SH enzyme ABHD16A, that functions upstream of ABHD12, and biosynthesizes lyso-PS lipids in the central nervous system (CNS) and immune system. Both ABHD12 and ABHD16A have high expression and activity in the CNS and the immune system (see the Figure below), and so do the recently characterized (deorphanized) lyso-PS receptors: GPR34, GPR174 and P2Y10. Our current work will investigate the connection between these lipid signaling networks and neuro-immunological processes using advanced “omics” techniques. Figure below shows a schematic representation of the ABHD12/ABHD16A-lyso-PS pathway.

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Investigating the role of a novel cancer associated gene

Uncovering underlying signaling mechanisms in adult and fetal hematopoiesis and their impact on ageing

Dr Sonam Mehrotra Intermediate Fellow 2016 Tata Memorial Centre Advanced Centre for Treatment, Research and Education of Cancer (ACTREC), Mumbai

Dr Satish Khurana Intermediate Fellow 2015 Indian Institute of Science Education and Research, Thiruvananthapuram

WEBSITE

WEBSITE The pool of hematopoietic stem cells (HSCs) required to keep up the production of all the blood cells in specific proportion is generated during fetal development. Multiple transient sites of hematopoiesis (blood cell development) appear during development (see figure) and this highly dynamic developmental process ends in establishing marrow of the freshly developing bones as the final site where blood cells will be produced for the rest of the life. Every stage of the life of an HSC, at least in part, is governed by extrinsic signals, which can come from immediate neighboring cells or a variety of humoral/chemical/physical factors (see figure below). Alteration in the dynamics of these factors results in age related deterioration of stem cell potential, leading to poor tissue function. HSCs happen to be one of the most studied of all the stem cells and are widely used in clinics for the treatment of a variety of hematologic and non-hematologic ailments. Evidently, expansion of these cells will be of use to clinicians, which has not been successful till now, an important underlying reason being, incomplete knowledge of key regulatory factors. In that direction, my lab will be working on mouse fetal liver (FL) as the model to uncover; (1) How the HSC pool is created during development and what are the mechanisms involved in symmetrical divisions? ; What are the extrinsic regulators that maintain the state of quiescence in adult HSCs? ; Molecular events that regulate functional changes in HSCs during aging ; Bioenergetic profile of the HSCs that leads to their differential function in different physiological states ; Outside-in integrin signaling in adult and fetal hematopoiesis

Detailed understanding of the molecular mechanisms required for maintaining normal cell functions and the identification of key molecules whose alterations result in cancer development are crucial for early detection and prevention strategies of cancer.

Replication stress is a primary cause of genomic instability leading to oncogenic transformation. Since non-cancerous cells employ a combination of robust DNA repair pathways and mechanisms to repair replication induced DNA lesions, replication stress is a common feature among cancer and precancerous cells but not observed in noncancerous cells. Exacerbating this property of cancer cells offers avenues for therapeutic intervention/s. Many components of Homologous-recombination (HR) mediated DNA repair, such as BRCA2 and RAD51 are involved in response to replication-stress where their functions are mechanistically different from their roles during HRdependent DNA repair. The roles of many other repair proteins during replication stress response remain poorly understood. It is therefore, imperative to understand the mechanistic details of the processes that prevent replication stress. My India Alliance-funded research embarks upon investigating the role of a novel cancer associated gene named BRCA2 and CDKN1A Interacting Protein (BCCIP), specifically, the characterization of its functions in prevention of replication stress. This knowledge will be etiologically important for BCCIP deficient cancers.

Structure, functions and recognition of long non-coding (lnc) RNA Dr Aditi Maulik Early Career Fellow 2016 Indian Institute of Science, Bangalore WEBSITE Long noncoding RNAs (lncRNAs) are large and diverse class of RNA molecules with > 200 nucleotides length that lack protein coding potential. LncRNAs have gained widespread attention in recent years due to their immense potential to regulate diverse biological processes.

Long Intergenic Non-coding RNAs (lincRNAs) are the largest class of lncRNAs in the eukaryotic genome, which originate from the intergenic regions. Although more than 3,000 human lincRNAs have been discovered using transcriptomic data and bioinformatics analysis, only a subset (less than 1%) have been functionally and mechanistically

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characterized in detail. These RNAs seems to be evolutionarily conserved at least in the mammalian genomes. One of the next challenges in biology is to ascertain the functions and mode of action of the newly discovered lncRNAs. My current project, funded by the India Alliance, propose to study the structural and mechanistic basis of select lncRNAs involved in gene regulation and telomere maintenance (e.g. TERRA, HOTAIR, lincRNA-p21 etc.). I aim to carryout a detailed phylogenetic, sequence conservation, secondary structure mapping, and recognition by effector proteins of lncRNAs using chemical and enzymatic probing, structural, and computational/bioinformatics approaches. This, I believe will be a timely study and the principles learned will be applicable on other lncRNA-protein systems.

Figure description: Schematic illustrating sweet taste processing in Drosophila: The axons of all peripheral gustatory receptor neurons terminate in the sub esophageal ganglion (SOG), the first relay for taste information in the fly brain. Labellar stimulation with sugars activates the sweet sensing Gustatory receptor Gr5a neurons (Green) that make synaptic connections with the first identified second order sweet gustatory projection neurons (NP1562 SGPNs-magenta) in the SOG. SGPNs axons relay sweet taste information to Antennal mechanosensory and motor center (AMMC) recently identified as an immediate higher-order processing center for sweet taste. Where and how the taste information for different taste modalities is conveyed from AMMC to higher brain center (mushroom body or Calyx) or back to SOG is not known.

Piloting a quality improvement intervention for the optimal medical management of patients with chronic heart failure (PANACEA-HF)

Understanding taste circuits and its modulation in Drosophila melanogaster Dr Pinky Kain Early Career Fellow 2016

Dr Deepak Y Kamath Early Career Fellow (Clinical and Public Health Fellowship) 2015

Regional Centre for Biotechnology, Faridabad WEBSITE

St John’s Medical College, Bengaluru

For all the animals, the sense of taste provides the ability to evaluate the quality of food sources. Food evaluation promotes ingestion of nutritious substances and discourages consumption of harmful substances. Food preference involves the peripheral taste system, but decision-making occurs in the central nervous system. I am interested in the gustatory system of Drosophila melanogaster to understand- how insects make the feeding decisions and the circuits involved?

Drosophila can sense same taste stimuli as mammals, including sugars, water, salts, acids, alcohols and bitter. These compounds facilitate acceptance or avoidance behaviors. Although innate taste behaviors may be modified by learning and experience. The simplicity of ligands and behaviors, along with the molecular, genetic, calcium imaging and electrophysiological approaches, allows one to examine taste processing from sensory input to motor output in a system that can also be modified by learning. For greater understanding of peripheral and central taste coding my research will focus on identifying neuronal taste circuits in the brain that influence feeding behaviors.

Physiological factors that can modulate taste signals, which are not well understood in insects. The results of this study can be applied for insect pest control and reduced pathogen transmission by insects that impact human health.

WEBSITE Heart failure is a condition characterized by a poor quality of life, owing to distressing smptoms, repeated hospitalizations and multi- morbidity.

Its prevalence in India is increasing. Heart failure patients tend to get re-hospitalized frequently due to fluid retention and severe breathlessness. Western studies that have employed ‘task-shifting’ interventions have shown that educating patients in self care (follow certain lifestyle measures, take their medications properly) and closer follow-ups, can reduce re-hospitalization rates, thus saving costs. While technology that bridges patient - care provider gap has been evaluated priorly in trials, we need more evidence to establish efficacy.

In this study, we will train lay health workers to educate patients with heart failure and/or their caregivers to record their own blood pressures and body weight as well as follow lifestyle modification, at the time point of discharge. The health worker will also enter the treatment plan (medications to be taken, dose, time of day, etc.) into the application at discharge. Centrally, the health worker will be equipped

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with a tablet. The mHealth system will be smart enough to alert the health worker about abrupt changes in body weight or uncontrolled BP. The health worker will work with the treating physician to take appropriate action (diuretic/ ACE-ARB/ beta blocker dose titration etc). The application will also prompt patients to take their medications. The health worker will make at least one home visit. Patients will be followed up for a year. We will employ an open label, individual patient, randomized controlled trial design (n = 230), with a 1:1 allocation ratio. Effects on all cause re-hospitalization and mortality will be documented, apart from a range of other clinical outcomes.

measures- score on the Coping Questionnaire, Family Member Impact Questionnaire, and Alcohol, Drugs and the Family Social Support Scale.

Ultimately, this work aims to help reduce the treatment gap, by taking care into the community in a culturally sensitive manner and giving a voice to a group that has traditionally been underserved.

Preliminary evaluation of Supporting Addiction Affected Families Effectively (SAFE) : a Pilot Randomised Controlled Trial Dr Urvita Bhatia Research Training Fellow 2016 (Clinical and Public Health Fellowship)

Sangath, Goa WEBSITE Apart from the direct consequences of problem drinking on the user, it negatively impacts their family members: including physical and mental ill-health: mood disorders, trauma, stress related conditions, and reduced quality of family relationships. India, the target of market expansion by producers of alcoholic beverages, has been experiencing a rapid increase in alcohol availability/consumption, lowering of the age of drinking onset, and higher levels of alcohol-related problems. This will cause a corresponding increase in prevalence of affected family members (AFMs), although this will be largely hidden because AFMs are a silent group; who deserve more attention in public health research.

Evidence-based interventions can help AFMs to reduce their symptom levels, and improve their coping methods. One such intervention, the 5Step Method, empowers AFMs by helping them reduce the strain experienced in living with a relative having alcohol problems, by reducing distress, and facilitating coping. However, in Low-and-Middle Income Countries (LMICs), two major barriers to making such psychosocial treatments accessible are the lack and inequitable distribution of skilled human resources for delivering such treatments and concerns regarding the contextual appropriateness and generalizability of treatments developed in ‘western’ cultural settings.

Evidence-based ways of making treatments accessible and acceptable in such low resource settings in LMICs are through adaptation of the treatment to overcome contextual barriers, and task-sharing (redistribution of tasks among health workforce) to address human resource shortages.

The Fellowship project follows the MRC framework for complex interventions, wherein a pilot Randomised Controlled Trial is being conducted to 1) contextually adapt the 5-Step Method using a systematic methodology to make it acceptable and feasible to be delivered by lay counsellors, and 2) to investigate preliminary effectiveness of the 5-Step Method by a primary outcome measurescore on the Symptom Rating Test, and secondary outcome

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INDIA ALLIANCE FELLOW IN SPOTLIGHT

Dr Vikram Mathews

Senior Fellow, Christian Medical College, Vellore Please tell us what you are working on and what impact do you hope it will have?

My area of research is centered on acute leukemia. There remain significant challenges in diagnosis, accurate prognostication and management of these conditions. Additionally, there are specific challenges in delivery of cost effective care in India and many parts of the developing world. A major problem in the management of acute leukemia is the high recurrence rate, especially in adults and the elderly.

While there has been a significant increase in the understanding of the biology of these malignancies the reasons for recurrence in spite of conventional therapy is not clear in most cases. More research is required to address the reasons and also ability to accurately predict relapse of acute leukemia. One area of special interest to our group is the role played by the micro-environment in the bone marrow in which these malignant cells reside in inducing resistance to therapy. Preliminary work by our group and others suggest that there is significant survival advantage and drug resistance to conventional therapy mediated by cells in the bone marrow microenvironment. Our preliminary data suggests that this phenomenon is seen in all types of leukemia though it would appear that the major mediators and pathways are different in different subtypes of leukemia. We have made significant progress in understanding the mechanism of microenvironment-mediated drug resistance to arsenic trioxide in acute promyelocytic leukemia (APL). In a recent publication from our group (Leukemia 2016) we have suggested a strategy in APL to overcome such resistance, which we have translated to the clinic. We hope that we will be able to identify similar strategies to overcome microenvironment mediated drug resistance to chemotherapeutic agents in other subtypes of acute leukemia. We feel this information along with additional work that we do in evaluating mechanisms of drug resistance will help direct our research on the use of novel agents and novel combinations of therapy to overcome such resistance. ​What ​ are some of the challenges ​ that remain in treating acute promyelocytic leukemia?

While APL is one of the leukemia which currently has the highest chance of long term cure, there still remain challenges in its management, especially in developing countries. Rapid diagnosis is critical to initiate therapy in this type of leukemia. Delay in initiating therapy can be fatal due to the high incidence of a unique bleeding diathesis seen only with this subtype of leukemia. In our country and many parts of the developing world making a rapid diagnosis validated by molecular techniques is still not widely available. Strategies and interventions that reduce the early mortality associated with this bleeding diathesis requires more work to be done. In the 10-20 percent of patients who do relapse after frontline therapy, the clinical outcomes remain poor especially in the absence of intensive therapies such as an autologous stem cell transplant.

What prompted you to transition from being a clinician to a researcher?

I had the fortune to train under Dr Mammen Chandy in my early years. He was a very enthusiastic teacher. Apart from being an excellent clinician he was very closely involved with laboratory work and encouraged all his students to have an interest in laboratory-related diagnostic and research work. His constant stimulating questions and encouragement was what facilitated my transition from being a clinician to a physicianscientist. Following completion of my training in Clinical Hematology I had the opportunity to do a post-doctoral fellowship at Washington University in St. Louis, USA. There under the close supervision of Dr.

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Timothy Graubert my basic science research career was born. I owe a lot to him and Dr. John DiPersio who helped me throughout my career and continue to support me in my work.

How can this transition be better facilitated and encouraged in India?

I think it is very important for young physicians to have exposure as part of their training to basic science work related to their area of specialization in Medicine, as is the norm in most developed countries. A number of physicians may find this exposure opening up new avenues for them. Additionally, short-term funding for projects to facilitate such exposure and also long-term funding to those who chose to take a career path as physician scientist should be easily available. At every stage both the organization for which they work and the funding agency that funds them should make efforts to provide protected time for research related activity separate from their clinical responsibilities.

While it should be obvious to all concerned on the benefits of having a physician-scientist in addressing research questions, in many cases an effort has to be made to educate administrators of many of our medical colleges on the benefits of encouraging this stream and the direct and indirect short and long term benefits of it.

How has Wellcome Trust/DBT India Alliance funding helped you and your research?​ In India many of the aspects about funding for physician-scientist that I mentioned would be ideal is part of Wellcome Trust/DBT India Alliance’s stated policy to encourage this group of researchers. As a result this policy I am a recipient of such an award and receiving this grant was central to me being able to take my work forward. I had been trying to get a similar grant for years before I applied to the India Alliance and the criticism, depending on the funding agency, was that there was too much basic science or too much clinical research for them to fund such a project. The ability to integrate my basic science work along with my clinical research was seamless for the India Alliance Fellowship and was in fact appreciated. Over and above the grant and funding, the India Alliance provides an opportunity to interact with scientists from within and outside the country and this in turn has helped me start a number of collaborative projects with other Fellows on this program.

What is the best advice you have received?

I consider Fr. Mervyn Coelho, my principal in my school days, my very first mentor. He had a keen interest in sports and was actively involved in training the school field hockey team. As the school’s goalkeeper and the last line of defense for my team he would stress that my only aim was to prevent the ball from going into the goal. He would say it was important to stay ‘focused’. During a game he would tell me to ignore the crowds, the shouting, the cheering, the jeering and even the opposing player coming towards you with the ball including his body and stick movements which are usually intended to deceive but instead to intensely focus on movements of the hockey ball and if possible to the seam of the ball and react only to that. That intensity of focus helped me in many a game and I continue to use that for problems in life and science as well.

What keeps you going every day?

Besides a lot of coffee, my family, students and work in that order.

Click here to find out more about Vikram’s research.

INDIA ALLIANCE FELLOW’S

RESEARCH HIGHLIGHTS

Decoding information processing in the brain Dr Nitin Gupta, Intermediate Fellow 2015 Indian Institute of Technology (IIT), Kanpur

Oscillatory neural activity has been found in nearly every part of the brain, in humans as well as in model systems. Oscillations represent the synchronized activity of multiple neurons in a brain region. Based on years of research, the neuroscience community has achieved good descriptions of how oscillations are generated and behavioral evidence that oscillations are important. But we still have little understanding of the mechanisms by which oscillations contribute to information processing in the brain. One prominent, but untested, hypothesis was that oscillations create periodic time windows in which a neuron collects inputs (“integrates spikes”, as a neuroscientist would say) from other neurons.

In this study, we used the insect olfactory system (sense of smell) to directly test this hypothesis. With paired extracellular and intracellular recordings and controlled stimulus manipulations in awake locusts, we demonstrated the presence of oscillatory integration windows in Kenyon cells of the mushroom body, an area considered important for learning and memory in insects. Then, with a computational model, we described how noise in the form of membrane potential fluctuations plays an essential role in the creation of integration windows.

The idea of integration windows was originally proposed following the observation of periodic inhibition. Our computational model, surprisingly, predicted that inhibition is not necessary to form integration windows. We tested this prediction experimentally by providing artificial oscillatory input to individual Kenyon cells through current injections into neurons (this technique allowed us to exclude network inhibition that usually accompanies odor-generated oscillations). Using the same technique, we also showed that the same population of neuron can form integration windows at multiple oscillation frequencies. In summary, our results show

that oscillation integration windows are real, simply generated (requiring only oscillatory input, without inhibition), and flexible (not tied to a particular oscillatory frequency).

Our findings point to features of neural responses that are important for coding information in the brain. Specifically, our results show, and explain why the precise timing of a spike with respect to the oscillation cycle can be an important determinant for the responses of neurons. The spikes that come within the integration window produce a larger effect on the receiving neuron; in other words, the integration windows allow some input spikes to carry more value than others, making the neurons highly sensitive to coincident inputs.

Our results provide new insights into temporal coding -- the idea that some information in the brain is contained in the precise timing of spikes, rather than just the number of spikes (rate coding). Although temporal codes have been observed in various systems, the mechanisms by which temporal codes are read by other neurons are an active topic of research. Our demonstration of oscillatory integration windows contributes to a mechanistic understanding of decoding of temporal codes.

Oscillatory integration windows in neurons. Nitin Gupta, Swikriti Saran Singh and Mark Stopfer. Nature Communications. Dec 2016 Figure (above) : A confocal microscopy image showing the dye-filled bundle of Kenyon cells in the mushroom body of the insect brain. Colors indicate depth

Regulating inflammatory immune response in Macrophages Dr Soumen Basak, Intermediate Fellow 2010 National Institute of Immunology (NII), New Delhi

A select set of dedicated intra-cellular signaling pathways determine the inflammatory response of the host to invading pathogens. These pathways are ubiquitous in nature, and yet various cell types give rise to strikingly different responses. To understand the mechanism underlying this cell type-specific control, we focused on the NF-kB signaling system, which plays a key role in the inflammatory immune response through canonical and non-canonical pathways.

In a collaborative study, we found that in infected fibroblasts and epithelial cells the NF-kB system integrates activation of both its pathways to induce an inflammatory response which eliminates the pathogenic substances. We also found that the NF-kB pathway crosstalk operated differently in white blood cells or macrophages. Interestingly, the NF-kB regulatory network was qualitatively identical between macrophages and fibroblasts.

Combining biochemistry and mathematical modeling, we instead identified quantitative differences in the biochemical rate parameters associated

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with the NF-kB signaling pathway between macrophages and fibroblasts.

Remarkably, these quantitative differences were sufficient for insulating the inflammatory NF-kB pathway from organogenic signals in macrophages. We propose that this insulation of canonical and noncanonical NF-kB pathways limit the deleterious effects of macrophagemediated inflammation.

Our study illustrates that despite the presence of identical signaling networks in cells of diverse lineages, emergent cross-talk between signaling pathways is subject to cell type–specific regulation.

Late-phase synthesis of IκBα insulates the TLR4-activated canonical NF-κB pathway from noncanonical NF-κB signaling in macrophages. Chatterjee B, Banoth B, Mukherjee T, Taye N, Vijayaragavan B, Chattopadhyay S, Gomes J, Basak S. Science Signaling. Dec 6, 2016

INDIA ALLIANCE FELLOW’S

RESEARCH HIGHLIGHTS

Protective effects of dietary potassium in bowel disease Dr Amit Awasthi, Intermediate Fellow 2012

Translational Health Science & Technology Institute, Gurgaon Our recent study in collaboration with our colleagues at Massachusetts General Hospital, Boston Children’s Hospital, Harvard Medical School and Johns Hopkins School of Medicine has found for the first time that dietary potassium reduces the risk of developing a chronic inflammatory disorder of the gastrointestinal tract medically known as Inflammation Bowel Disease (IBD).

Crohn’s disease (CD) and Ulcerative Colitis (UC) that constitute IBD are caused by imbalance between disease promoting (Th1 and Th17) immune cells, and disease suppressing (Foxp3+ T-regulatory) immune cells. These cells normally remain in homeostatic balance resulting in a “healthy bowel” free of disease. However, in response to environmental and gut microbial triggers, T cell immune balance is disrupted and disease promoting T cells leading to inflammation resulting in bowel injury requiring lifelong medical therapy. Why the gut environment is altered in IBD is a focus of scientific investigation. In our study, we specifically addressed the role of smoking, diet and hygiene, which in turn can affect the gut microbial community, in IBD.

Our results suggest that dietary intake of potassium but not sodium is associated with decreased risk of developing Crohn’s disease. Our data further demonstrated the underlying mechanism of potassium for such protective effect in IBD and demonstrated that the extracellular potassium modifies the T-cell response and promotes the generation of disease preventing T-cells. The long-term implication of these findings is that potassium rich diet has the ability to modulate the immune response and autoimmunity via induction of Foxp3-mediated T cells tolerance. We know the precise mechanisms by which dietary/extracellular potassium may modulate immune tolerance through regulating the Th17/Tregs balance.

Identification and Characterization of a Novel Association Between Dietary Potassium and Risk of Crohn’s Disease and Ulcerative Colitis.

Hamed Khalili, Sakshi Malik, Ashwin N. Ananthakrishnan, John J. Garber, Leslie M. Higuchi, Amit Joshi, Joanna Peloquin, James M. Richter, Kathleen O. Stewart, Gary C. Curhan, Amit Awasthi*, Vijay Yajnik* and Andrew T. Chan*Frontiers in Immunology. November 2016

New insights into the role of molecular messengers, Inositol Pyrophosphates, in regulating cellular traffic

Ms Manasa Chanduri and Dr Rashna Bhandari (Senior Fellow 2010)

Laboratory of Cell Signalling, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad The role of small molecules in maintaining cellular homeostasis is wellestablished. Inositol Pyrophosphatase 7 (IP7) is one such molecule that consists of an inositol ring decorated with seven phosphate groups (see Figure). The six alpha phosphates in IP7 are attached directly to the carbon atoms on the ring, and a seventh (beta) phosphate is attached to one of the alpha phosphates. Mammals have three IP6 kinases (IP6K1/2/3) that catalyse the synthesis of IP7 from IP6 and ATP (see Figure). IP7 participates in many vital cellular functions such as apoptosis, DNA repair, ribosome biogenesis, and energy homeostasis. In some of these pathways, IP7 has been shown to modulate protein function by directly transferring its β-phosphate to a phosphorylated serine residue leading to protein ‘pyrophosphorylation’.

and kinesin motor driven trafficking of vesicles towards the cell periphery. We decided to explore whether IP7 affects dynein-driven vesicle transport from the cell periphery to the interior, i.e. towards the minus-end of microtubules. Upon examining mammalian cells lacking IP6K1, which have a 70% reduction in IP7 levels compared with normal cells, we identified a delay in dynein-dependent sorting of vesicles containing the iron-transport protein transferrin. We also noted slower motility in vesicles moving from the cell membrane towards the perinuclear region, and disruption of Golgi morphology, a classic readout of dynein dysfunction.

The transport of fluid-filled sacs or vesicles within cells is critical forintracellular and intercellular communication. Earlier studies on the cellular roles of IP7 revealed its importance in some intracellular vesicle trafficking processes in mammalian cells including insulin exocytosis,

We found that dynein intermediate chain (IC), a subunit of the dynein complex, is pyrophosphorylated by IP7 (see Figure). IC interacts with the p150Glued subunit of the protein complex dynactin, which in turn

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We collaborated with India Alliance Senior Fellow, Dr Roop Mallik at TIFR, Mumbai, to study the effect of IP7 on dynein-driven motility of isolated vesicles. Dr Mallik’s lab noticed that in comparison with wildtype amoebae, endosomes derived from amoebae lacking IP7 show a decrease in dynein-dependent movement towards the minus-end of microtubules, and a corresponding increase in kinesin-directed movement towards the plus-end. It is known that a continuous tug-ofwar between these two opposing motors on an endosome that decides its direction of movement. These experiments also revealed no change in vesicle velocity, indicating that motor function was not compromised, and suggested that compared to their wild-type counterparts, amoebae lacking IP7 recruit fewer dynein molecules to endosomes.

helps in the recruitment of dynein to vesicle membranes.

INDIA ALLIANCE FELLOW’S

RESEARCH HIGHLIGHTS A disruption in dynein-dynactin interaction has been shown to result in phenotypes similar to those we observed in cells with low IP7 levels. In fact, we found a decrease in dynein-dynactin association and reduced recruitment of dynein to membranes in IP6K1 knockout cells.

Our study highlights an important role for IP7 in dynein-driven trafficking. We propose that IP7-mediated pyrophosphorylation acts as a switch favouring dynein attachment to membranes, thereby providing the push needed to move vesicles to the minus-end of microtubules. Our work has also provided a boost to research on serine pyrophosphorylation by IP7. This aspect of the work was emphasized in a commentary on the paper by Dr Adolfo Saiardi from University College London, titled "Protein pyrophosphorylation: moving forward". The

commentary highlighted how "this work increases our awareness of this modification, underappreciated by the scientific literature but probably not by the eukaryotic cell".

Inositol hexakisphosphate kinase 1 (IP6K1) activity is required for cytoplasmic dynein-driven transport. Chanduri M, Rai A, Malla AB, Wu M, Fiedler D, Mallik R and Bhandari R.. Biochemical Journal (2016) Commentary: Protein pyrophosphorylation: moving forward. Saiardi ABiochemical Journal (2016) 473: 3765-3768.

First comprehensive description of druggable mutation spectrum in lung cancer patients in India Dr Amit Dutt, Intermediate Fellow 2011

Tata Memorial Centre - Advanced Centre for Treatment, Research and Education in Cancer, Mumbai The observed mutational diversity underlying cancer genomes is in line with the varied clinical response found in cancer patients based on their ethnicity, divergent genetic structure and exposure to environmental factors. Therefore, besides the unmet need for additional therapeutic targets in lung cancer patients, it is equally important to screen for and profile known therapeutically targetable gene alterations across different populations to acquire a better understanding of this landscape of variability. In the study published in Annals of Oncology by our group with other colleagues from ACTREC, Tata Memorial Centre, we addressed this germane and basic deficiency in the field by profiling for known actionable mutations in 363 Indian lung cancer patients using advanced sequencing technologies and Mass Spectrometry.

Dhamne, D. N. Iyer, P. Upadhyay, B. Mohanty, P. Chandna, R. Kumar, A. Joshi, V. Noronha, V. Patil, A. Ramaswamy, A. Karpe, R. Thorat, P. Chaudhari, A. Ingle and A. Dutt. Annals of Oncology. Dec 2016

Our findings present the first comprehensive description of druggable mutation spectrum in lung cancer patients, which interestingly occurs at markedly distinct frequency in Indian population compared to the previously known Caucasian and East-Asian populations. The crucial findings from this study form the base to rationalize targeted therapy among Indian lung cancer patients. This study also presents the first systematic evidence for occurrence of recurring mutations in a receptor tyrosine kinase gene, fibroblast growth factor receptor 3 (FGFR3) in 20 of 363 (5.5%) lung adenocarcinoma patients studied. FGFR3 mutations have been reported in bladder carcinoma, lung squamous cell carcinomas (a different subtype of lung cancer), and cervical cancer, but were found to be largely absent in lung adenocarcinoma patients of Caucasian origin.

More recently, consistent with our previous study, presence of frequent FGFR3 mutations, have been tangentially referred to, also exist in Korean lung adenocarcinomas patients. However, details of the mutations described in this study remain to be defined. Thus, our finding along with the indirect reference of similar mutation in Korean population suggests an emerging role for FGFR3 mutations in lung adenocarcinoma that are more likely to be predominant among the Asian population In this study we provide detailed mechanistic characterization of the novel FGFR3 activating mutations found in lung adenocarcinoma patients using elegant genetic, biochemical and mouse-xenograft experimental techniques. This study concludes that the FGFR3 mutations found in lung adenocarcinoma patients of Indian origin are oncogenic, and form a subclass of FGFR inhibitor-sensitive patients largely distinct from those harboring other druggable mutations in lung cancer, such as these in EGFR, KRAS, or EML4-ALK mutations.

Interestingly, the FGFR3 mutations appear to be significantly higher in proportion in patients less than 45 years old (P value = 0.048), and show a trend towards better overall survival of 17 months (P value= 0.5) compared to patients lacking actionable alterations or those harboring KRAS mutations.

Taken together, these findings implicate FGFR3 as a novel and an effective therapeutic target in treating lung adenocarcinoma patients.

Drug-sensitive FGFR3 mutations in lung adenocarcinoma. P. Chandrani, K. Prabhash, A. Choughule, R. Prasad, V. Sethunath, M. Ranjan, P. Iyer, J. Aich, H.

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Figure: Top: Pie-chart representing frequency of clinically relevant genes observed in 363 Indian lung adenocarcinoma patients. Bottom: PET scan to assess 18F-FDG uptake by tumors obtained by subcutaneous injection of mouse embryonic fibroblast cells (NIH/3T3) clones over expressing FGFR wild type and mutant constructs ~2 months. Selective FGFR inhibitor BGJ-398 or vehicle treatment was administered orally in mice after tumor size reaching ~100-200 mm3, for 21 days. A readout for relative 18F-FDG uptake is shown by a gradient color code with red indicating as maximum uptake. 18-Fluoro-deoxyglucose positron emission tomography or 18F-FDG/PET scan is used for imaging tumors and is based on the amount of glucouse uptake by tumours which reflect its metabolic state.

INDIA ALLIANCE FELLOW’S

RESEARCH HIGHLIGHTS

The balancing act in membrane turnover: an enzyme that links endocytosis to membrane recycling Dr Raghu Padinjat, Senior Fellow 2014

National Centre for Biological Sciences, Bangalore

By Anusha Krishnan Blink. When you wake up, the first thing you do is open your eyes and see.

All cells have surface membranes, and this membrane is especially important in the light-sensitive cells of the eyes in your body. Within your eyes are millions of photoreceptors - nerve cells that capture light to form images of the world around you. The surface membranes of these nerve cells are packed with rhodopsin, a protein that detects light. These are the light-sensing membranes of the eyes that absorb packets of light to trigger nerves causing the sensation of sight.

Once triggered by light, rhodopsin molecules on the surface membrane must be 'reset' in order to sense light again, a process that occurs within the cell. This requires rhodopsin to be moved into the cell and for 'reset' rhodopsin to be recycled back onto the surfaces. Therefore, to function normally, the light-sensing membranes in these cells undergo constant recycling to restore the light-detectors they carry.

Scientists from the National Centre for Biological Sciences (NCBS), Bangalore, and the Babraham Institute in UK have recently found a critical player essential for proper membrane recycling. Using the lightsensitive membranes of fruit-fly eyes as a model system, the researchers have discovered that the enzyme Phospholipase D or PLD is necessary for membrane recycling to sustain normal sight.

The resetting of rhodopsin molecules begins with a process called endocytosis, where the cell pinches off parts of its surface membranes into structures called endosomes. The rhodopsin in these endosomes is eventually recycled back onto the cell surface for further events of light detection. Since a photoreceptor's sensitivity depends on how many rhodopsin molecules it has on its surface, membrane turnover in these cells is critical in preserving normal eyesight.

"You can think of endocytosis and membrane recycling as two arms of the membrane turnover process," says Raghu Padinjat from NCBS. "There needs to be a balance between the two, or else the size of the membrane will shrink - a condition that could lead to retinal degeneration in the eyes. This is actually seen in an inherited genetic disease, a rare disorder called Best's macular degeneration," he adds.

progressively less sensitive to light. Without PLD activity, the retina gradually degenerates and mutant flies go blind.

Padinjat's team chose to use the fruit fly eye as a model system since it has many ideal characteristics for studying membrane turnover. This is because the light-sensing parts of fruit fly photoreceptors are highly expanded, forming a structure called the rhabdomere. When exposed to light, changes in the size of this membrane can be distinctly visualised through electron microscopy. Furthermore, due to the genetic tractability of the system, the researchers were able to clearly identify PLD as an essential component regulating membrane turnover. "The enzyme PLD converts a molecule called phosphatidylcholine into phosphatidic acid or PA, which is implicated in membrane turnover. However, PA is also produced by other enzymes, and our study conclusively shows that the PA regulating membrane turnover was produced by PLD," says Rajan Thakur, a researcher from Padinjat's group and the primary author of a publication in the journal eLife that reports these results.

Despite identifying a key player in the membrane turnover process, Padinjat's team believe that many more gaps need filling in understanding the phenomenon. For example, the work shows that the PLD activity in photoreceptors is light-activated, but how this happens is still unresolved.

"The light receptor, rhodopsin is on the membrane surface, and can detect light when the surface of the cell is illuminated. But PLD, which is also light-activated, is somewhere inside the cell. So how is the information about perceived light conveyed to PLD for it to get activated?" asks Thakur. "We also need to fill in blanks about how PA actually affects membrane recycling and the turnover process. Our finding has opened up more questions to answer in the membrane turnover process," he adds.

However, the connection between endocytosis and the eventual recycling process to maintain photo-sensitive surface membranes have remained unclear - until now. A collaborative study from Padinjat's laboratory at NCBS and the Babraham Institute in UK, has found that a well-known enzyme called Phospholipase D or PLD plays a central role in linking endocytosis to membrane recycling.

But the results from this study are not limited only to membrane turnover in the light-sensitive membranes of the eyes. Membrane turnover is a critical mechanism that maintains cell surface area. In cells that have expanded cell surfaces such as those lining the airways of the lungs or the nutrition-absorbing cells of the gut, maintaining cell surface area is essential for their normal function. Even processes such as cell migration have extensive endocytosis and membrane recycling events that must be tightly regulated.

"Therefore, regardless of what the cell type is, there need to be mechanisms to couple endocytosis with recycling of membrane," says Padinjat. "And that is the importance of our work - we define a mechanism by which cell membrane size is regulated," he adds.

Using fruit fly photoreceptor cells as a model system, the team has found that when these cells are exposed to light, PLD is switched on, and that its activity is essential in coupling endocytosis with recycling of rhodopsin back to the cell surface.

The research described in this article has been published as a paper titled "PhospholipaseD activity couples plasma membrane endocytosis with retromer dependent recycling" in the journal eLife in November 2016.

In mutant flies that lack PLD in their photoreceptors, the endocytosis process is unlinked from membrane recycling. When exposed continuously to light, the cell surface of photoreceptors in mutant flies gradually shrinks, with reducing rhodopsin levels that make it

( This research story was originally posted on NCBS website) Image credit : Wellcome Images

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INDIA ALLIANCE CALL FOR APPLICATIONS

Event support

Application deadlines: 15 February and 15 July 2017

About India I EMBO Symposia

Application process

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.

• Applications for India | EMBO Symposia will be accepted twice in 2017 and must be submitted through the online system. Organizers should apply at least 6-12 months before the proposed date of the meeting.

The deadlines for applications are 15 February 2017 and 15 July 2017, 14:00 CEST.

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.

• Applicants will be asked to complete an online and an offline application form.

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.

• 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.

Required documentation Applicants will be asked to provide: • A list of organizers • Proposed title and topic of the meeting • Reasons for holding a meeting on the proposed topic • Information on any competing or similar meetings held in the current, proposed or following year • Proposed date and location • List of proposed speakers/instructors • Draft programme • Participant selection criteria and number of participants • Proposal for the position paper • Information on the practical component of the meeting (if applicable) • Draft budget

• 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.

Selection process

Eligibility

The selection process involves the following steps: • All incoming applications are screened to ensure eligibility requirements are met.

• 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).

• 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.

For any enquiries, please write to workshops@wellcomedbt.org

16.

INDIA ALLIANCE

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REPORT

Young Investigators Meeting – Chicago (YIM-C) 2016 21-23 September, 2016 University of Chicago, USA

Report by Dr Piyush Behari Lal, Sci-ROI Organizing Committee​ Science & Research Opportunities in India (Sci-ROI), a volunteer driven non-profit organization, organized Young Investigator Meeting-Chicago 2016 from 21-23 October 2016 , which brought together nearly 150 young Indian research scientists and engineers from all over USA and 30 leading academics, policy makers and scientists in India and USA to discuss new research and industry opportunities in India. The event was held at University of Chicago, Chicago which was conceived by Prof Aseem Ansari, University of Wisconsin–Madison, USA and Prof L Shashidhara, Indian Institute of Science Education and Research, Pune, India. The event was jointly hosted by Consulate General of India, Chicago and the University of Chicago. The event was supported by the Welcome Trust/DBT India Alliance, University of Wisconsin-Madison, InNOW LLC and WINStep Forward.

With a goal to introduce young Indian research scientists and students in USA to institutional heads, policy makers and entrepreneurs from India and USA, the YIM-C 2016 was launched on 21st October, 2016 at the Indian Consulate in Chicago. by Dr Ausaf Sayeed, Consul-General of India in Chicago. In his inaugural remarks, Dr Sayeed, mentioned several multilevel collaborative initiatives between India and USA in various disciplines. He also invited the attendees to participate in PM Narendra Modi's Flagship Programs, including ‘Make-in-India’, ‘Skills India’, ‘Digital India’, and ‘Green India’, and to engage with the Indian government through MyGov.in.

In the keynote address, Dr R Brakaspathy, Secretary, Science and Engineering Research Board (SERB), India, introduced the audience about the transformative new extramural research funding opportunities and collaborative programs for individual researchers as well as for institutions. The session was also addressed by Dr Mangala Sharma, Program Director, Office of International Science and Engineering, National Science Foundation, Mr Jonathan Ward, Principal Commercial Officer, US Department of Commerce, Consulate General of US in India, Kolkata, Dr Shekhar Mishra, Fermi National Accelerator Laboratory, Mr Vinny Gupta, Chair, Ohio Board of Regents and Prof Aseem Ansari, the Founder-Director of the Khorana and S. N. Bose programs of WINStep Forward. The speakers conveyed the immediacy and importance of the growing India-US collaboration initiatives and the efforts of the Government of India to include the various segments of the scientific community and the industry to accelerate the pace of development across several sectors in India. The inaugural launch at the Indian Consulate was followed by two days of scientific presentations and interactive panel sessions at the University of Chicago campus. The opening remarks at the second session were delivered by Prof Aseem Ansari, which was followed by welcome notes from Dean and Director Nancy Schwartz and Vice-Provost Melina Hale of the University of Chicago. The first session “Research and funding opportunities in India” started with a presentation by Secretary, SERB and Dr Shahid Jameel, CEO, Wellcome/DBT India Alliance. The speakers described various fellowships and funding opportunities available to individuals interested in returning to India.

The second session started with an inspiring talk from Dr Sam Pitroda, who has served as advisor to the Indian Government for many years. The

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session further explored emerging trends from Institutional perspectives, where participants got invaluable career tips from experienced scientist and heads of institutes, which included, Prof Dipankar Chatterji (IISc, and former Chair, JNCASR), Prof Ajit Chaturvedi (Deputy Director, IIT Kanpur), Prof Sudhanshu Vrati (Executive Director, Regional Center for Biotechnology), Prof Ramaswamy (Institute for Stem Cell Biology and Regenerative Medicine; InSTEM) and Dr Shekhar Mishra (Deputy Project Manager, PIP-II Indian Institute and Fermilab Collaboration).

The panel discussed about building a research career in India, the opportunities and challenges faced by young investigators. YIM-C participants presented their perspective on the challenges they face while applying for faculty position and establishing a connection with Indian officials at various levels and stages as well. The panel also recommended aspirants to apply early and connect with host institutions in India. They were also reminded of the growing competition and the challenge for them to be truly globally competitive irrespective of their international experiences. On being asked about the serious challenges that need to be addressed, including that of basic supplies, research funds and quality of research, Dr Brakaspathy said, although the government is making an effort to arrest shortcomings, it should enhance measures to tackle these issues to ensure the Indian talent returns to the country.

Dr Arindam Mondal, who was recently appointed as Assistant Professor at IIT, Kharagpur and Dr Poulomi Roy (Assistant Professor, BITS, Mesra) presented various challenges in finding academic jobs and establishing a laboratory in India. During the “Innovation landscape - Make in India / Entrepreneurship / US-India ventures” session, Mr Johnathan Ward, United States Consulate in India, highlighted United States’ and India’s priorities of generating sustainable economic growth, creating jobs, improving the business and investment climate, enhancing livelihoods, and sustaining the rules-based global order. Prof Sampath Ramesh (Kellogg School of Business, Northwestern University) emphasized on fundamental needs of the less privileged community. Michael Rosen, Managing Director of Rosen Biosciences, LLC and Co-founder and Board of Directors, Illinois Biotechnology Industry Organization (I-BIO) discussed science parks and how they fit into the life science industry in India. Dr Gopal Dasika, Vice President, Biologics Development Center at Pfizer engaged the audience with his personal story of moving as faculty from UT Medical Center at Houston to India. Dr Dasika stressed, “candidates contemplating relocating need to clearly identify the motivations and strongly consider familial needs so as not to develop cold feet at the very end after having engaged in a long-tedious recruitment process”. Dinesh Jain, Founder CEO, Aagami, Inc., provided an overview of various opportunities, initiatives and trends in India today. Dr Lukhwinder Hundal, CTO, InNow, LLC, concluded this session by presenting the audience with various commercial initiatives to clean water of effluents. The growing need for clean water, the large unserved population of India, and the dearth of wastewater treatment facilities were underlined as part of his presentation.

INDIA ALLIANCE

Event support

Panel discussion at the YIM-C meeting

Prof LS Shashidhara, Prof Siddhartha Roy, Director Bose Institute and former Director of Indian Institute of Chemical Biology -CSIR labs, Prof S Ramaswamy of Institute for Stem Cell Biology and Regenerative Medicine(InStem), Bangalore, Prof Tapas Kundu, JNCASR Bangalore, and Prof Yamuna Krishnan, University of Chicago continued the session on “Emerging trends based on institutional perspectives-II” on the final day.

The following session was dedicated again to Innovation landscape Make in India / Entrepreneurship, where Prof Arun Goyal emphasized on other aspects of research where youth can play a big role and become successful entrepreneur. He insisted and encouraged to focus on sectors like waste management, food processing and disaster management which are the need of time in a country like India. Beside aforementioned eminent speakers, the event also was fortunate to have representatives from several Midwestern universities.

In his concluding remarks, Prof Aseem Ansari talked about how the Bose and Khorana programs, administered by WINStep Forward, grew organically and provided the background that led to the genesis of SciROI, a volunteer-driven organization. He also urged young scientists to engage and couple their career aspirations with efforts directed towards

the betterment of our society and country. At the end, participants interacted with Sci-ROI organizing committee for a follow-up event on Technology, Innovation and Entrepreneurship in 6 months and the repeat of YIM-C event at the end of summer in 2017.

Event received enormous response from many institutions and national labs across the Midwest-USA. The young researchers from different streams got a chance to interact with leading scientists, entrepreneurs, policy makers and learnt about available and upcoming academic and entrepreneurial opportunities in India directly from the head of institutes/department and entrepreneurs. The talks from speakers/scientists from diverse backgrounds were very informative, inspiring and helped young scientists to understand the process to enter research field in India. It was recommended to apply early, and get in touch with institutions in India at least a year before moving. However, the event clearly conveyed that India is not keen on hiring suitcase scientists; only those seriously considering relocating are being considered.

REPORT

19th Transcription Assembly Meeting 2016 8-9 November 2016 Bose Institute, Kolkata

Report by Dr Smarajit Polley, India Alliance Intermediate Fellow, Bose Institute, Kolkata The 19th version of Transcription Assembly Meeting was held at Bose Institute, Kolkata from 8-9 November, 2016. The event was organized in association with Saha Institute of Nuclear Physics and CSIR-Indian Institute of Chemical Biology, Kolkata.

scientific interest, and expertise related to gene expression came together to share their experiences, and insights on this exciting subject.

In the late ‘90s, Indian scientists working on different aspects of prokaryotic and eukaryotic transcription processes felt the urge to conduct an informal meeting to share and discuss the progress of individual efforts in understanding the complexity and regulatory aspects of these key mechanisms of life. Hence, an informal group was formed, and the ‘Transcription Assembly Meeting’ set forth its journey in 1997 at Centre for Cellular and Molecular Biology (CCMB), Hyderabad. These meetings are characterized by intense, close, and informal interactions.

Participation in this meeting is purely on invitation basis. This year the meeting was expanded to include a number of newcomers along with the long-term members and regular attendees.

Conversion of genetic information into functional protein molecules is a multistep process, at the top of which lies the process called Transcription. Understanding the basic mechanism underlying transcription has come a long way. However, details of the regulatory processes and the importance of these events in organismal life cycles are bringing newer and ever exciting facts into light. For example, even though sequence specific DNA binding is a key event in a specific transcription factor dependent regulation of gene expression, it is now clear that context dependent regulatory mechanisms hold the key to the fate of these events. Genome organization, epigenetic modifications and inheritance of epigenetic marks, tissue and cell type specificity, status of the cells, each play pivotal role in shaping the outcome of gene expression events in cells. At this meeting, researchers with diverse

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The meeting included different scientific sessions with the following themes: DNA Damage and Epigenetics; Prokaryotic Transcription; Virus; Disease Biology; Regulatory RNAs and Miscellaneous session that covered an array of topics ranging from transcriptional regulation of stress response in plants to synthetic biology. Twenty four students and postdocs from different Institutes in India presented posters. Four of the posters from student participants were chosen for short talks (based on poster presentation), and were ranked on the basis of both poster, and oral presentation for the best poster awards (cash prize). Apart from students and Principal Investigators, young investigators, and postdoctoral researchers also presented their work in the form of short talks. Overall, a vibrant atmosphere prevailed at the meeting where everyone was able to freely interact with senior and established scientists, forging collaborations, and asking for expert opinions on various aspects of their day-to-day research as well as future plans.

During the last session of the meeting, long-term members of the meeting as well as the newcomers engaged in a deliberation to consider renaming “Transcription Assembly Meeting” to “RNA Meeting of India”. As described earlier, it is becoming hard to define a clear boundary between transcription, epigenetics and RNA biology. And, a meeting with a solo theme may not be adequate to address many of these new areas, whereas a theme with mixed interests may cater to the need of the moment, and to a diverse audience. Concluding session of the 19th Transcription Assembly Meeting opened the door for this consideration.

INDIA ALLIANCE

Event support REPORT

3rd Annual BSBE Winter Workshop, 2016 Neural Systems: from circuits to behaviour

17-18 December, 2016 Indian Institute of Technology Kanpur Report by Dr Nitin Gupta, India Alliance Intermediate Fellow at IIT Kanpur

The 3rd Annual BSBE Winter Workshop was held during Dec 17-18 at IIT Kanpur. Every winter, the Biological Sciences and Bioengineering department (BSBE) organizes a two-day workshop on a specific theme, with the last two focusing on “Neurobiology of disease”, and “Musculoskeletal disorders”. This year, the 3rd workshop in the series focused on the theme, “Neural Systems: from circuits to behaviour”.

To understand brain function and brain disorders, it is important to obtain a mechanistic understanding of the brain at different scales of organization. The recently launched global brain initiatives such as the Human Brain Project and the US BRAIN initiative have increased the visibility of brain research, kindling an interest among the students.

However, neuroscience is often missing from undergraduate and graduate curricula in Indian universities, making it difficult for students to get exposure to the field. This workshop brought together experts from diverse disciplines within neuroscience to discuss recent findings in the field and to expose students from diverse backgrounds to cuttingedge neuroscience pursued in India.

The two-day event had 12 speakers from different institutes in the country, 34 registered student participants, and about 20 unregistered participants from the IITK community. The workshop started with a demonstration session (we thought that students new to the field would be better equipped to appreciate the data presented in research talks if they first gained some familiarity with the techniques used to generate the data). Aarush Mittal, a PhD student at IIT Kanpur, showed how a neuron can be modeled in the computer, and how its firing rate is determined by its various membrane properties. Students then visited our neurophysiology lab to see ongoing experiments, where Shefali, another PhD student, showed how to dissect the brain of a fruit-fly or a mosquito and how to make glass electrodes; Swikriti showed the setup for extracellular recordings from the antenna of an insect; and Pranjul showed the technique and equipment used for whole-cell patch-clamp recordings from neurons. Later in the day, the participants also toured other labs in the BSBE department.

mechanical engineering at IIT Kanpur, presented his work on the design and evaluation of robotic arms for patients who have suffered loss of motor functions due to strokes. IA Fellow, Vatsala Thirumalai from NCBS described her recent work on the network dynamics that shape the responses of neurons in the cerebellum region of the brain. Jonaki Sen from IIT Kanpur described her work on the development of the vertebrate brain. Sheeba Vasu from the Jawaharlal Nehru Centre for Advanced Scientific Research presented her work on the circuits in the fruit-fly involved in control of sleep-wake cycles. Another IA Fellow, Suhita Nadkarni from IISER Pune described a computational model of the molecular pathways involved in signaling inside the brain. On the cognitive and behavioural side, Ark Verma from IIT Kanpur presented his findings on specialization of the left and the right brain hemispheres for specific functions, while Supriya Ray (IA Intermediate Fellow) from University of Allahabad discussed the mechanisms underlying behavioural choice.

The invited speakers presented on a range of topics, from molecular basis of the development of neural circuits, to higher cognition and neuro-rehabilitation. To name a few, Ashish Dutta, a professor of

The workshop also featured a panel discussion by Joby Joseph (University of Hyderabad), SP Arun (IA Intermediate Fellow, Indian Institute of Science) and Nitin Gupta (Intermediate IA Fellow, IITK) on the topic “Do we have the right tools to understand the brain?”. Inspired by a recent article that provokingly asked whether a neuroscientist can understand a microprocessor, this informal session prompted the participants to discuss the powers as well as limitations of the techniques that are currently used in neuroscience.

The student feedback on the workshop was largely positive, underlining the need for more such events. Not surprisingly, the demonstration session was the most liked part of the workshop, with many students expressing a desire for longer experimental sessions in future events.

Overall, the workshop made apparent the enthusiasm for systems neuroscience research in India, and that bodes well for the development of this nascent field in the country.

Workshop participants in the labs

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INDIA ALLIANCE workshops

SCIENCE COMMUNICATION Image credit: Dr Ranjana Sarma, picture taken at SASTRA University

3rd Science Communication & Career Workshop 16 November 2016, Jiwaji University, Gwalior The third Science Communication and Career Workshop with our partners Nature India and Nature Jobs was held at the 15th All India Cell Biology Conference & International Symposium on Functional Genomics and Epigenomics at Jiwaji University, Gwalior on 16 November 2016. The workshop which was a held a day before the conference, was attended by around 75 PhD students and postdocs from 36 institutions. In addition to brief lectures and case study discussions on Manuscript writing, research ethics and presentation skills, participants also engaged in a discussion with editor of Nature India, Ms Subhra Priyadarshini on

various aspects of communicating research to the media and the public .

Subhra also gave an overview of science journalism as a career option.

As always, short science story competition at the workshop was very popular and saw active participation.

To request this workshop at a conference, send your request to workshops@wellcomedbt.org

FameLab India - SciComm Workshops 27 November - 16 December 2016, Multiple locations British Council India and Cheltenham Festivals, UK brought world’s biggest Science Communication competition, FameLab, to India in September 2016. The Wellcome Trust/DBT India Alliance was one of the supporters of this initiative along with Nature India and IndiaBioscience.

FameLab is an international competition which runs in over 30 countries and came to India for the first time and is aimed at improving science communication and to develop charismatic early career scientists and engineers who can actively engage with their peers and the public.

The competition was open to anyone who is a student of science, mathematics or engineering, a scientist or researcher, a lecturer in science, mathematics and engineering subjects or someone who is applying science, mathematics and engineering in Industry or Government, between the ages of 20 and 40

training from FameLab winner, science communicators and scientists on various topics such as, public engagement with science, popular science writing, ethics in research and scientific communication. India Alliance Fellows, Drs Satish Khurana ( IISER Thiruvananthpuram), Abhijit Majumder (IIT Bombay), Sheetal Gandotra (CSIR- IGIB New Delhi) and Guruprasad Medigeshi (THSTI Faridabad) were among the workshop mentors.

Top three contestants from each of the regional workshop will be competing at the final FameLab India competition to be held next month. Winner of FameLab India would then participate at the Cheltenham Science Festival in the UK to represent India at the FameLab International grand final.

Watch this space for more information on these competitions.

Before the regional competitions, which were held in Thiruvananthpuram, Bhubaneswar, Delhi and Mumbai, shortlisted contestants took part in a three-day masterclass where they received

Find out more about FameLab India here

18th SciComm101 workshop

22 December 2016, SASTRA University, Thanjavur On 22 December 2016, India Alliance’s SciComm101 reached the rice bowl of Tamil Nadu. Our 18th SciComm101 Workshop organized at SASTRA University, was attended by around 70 participants, mostly senior PhD students and junior postdocs from SASTRA University and 12 other institutions across Tamil Nadu, such as University of Madras, Central University of Tamil Nadu, Bharatidasan University, Sathyabama University, SRM University, Rajah Serfoji Government Arts College, and CSIR-Central Leather Research Institute. Apart from the conventional modules on research ethics, presentation skills, manuscript writing, and grant writing, a special session on alternate careers in science received many questions

from the participants.

Next SciComm101 Workshop will be held at Manipal University on 13 February 2017. Please visit our website for more information on these workshops To request one at your institution, send your request to workshops@wellcomedbt.org

Upcoming workshop

2-day Science Communication Workshop, Hyderabad on 2-3 March 2017 Applications submitted for this workshop are currently under review. Selected participants will be informed by third week of January.

For more details on our Science Communication workshops, visit our website

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INDIA ALLIANCE

PUBLIC ENGAGEMENT

REPORT As part of the ongoing “Voices for Health” public engagement series, the Wellcome Trust/DBT India Alliance in partnership with Centre for Environmental Health (CEH, Public Health Foundation of India), Happy Hands Foundation and Salaam Balak Trust organized a public event around the problem of air pollution on 13 December. The event that was held at a popular public venue in Delhi, highlighted the problem of air pollution and provided solutions through informational pamphlets, exhibits and creatively through display of traditional Indian paintings made by school students, street theatre performance by children from Salaam Baalak Trust, and puppet show performed by the women of Kathputli colony in Delhi. The central plaza at Select City Walk where the event was held also had stalls with interesting hands- on- activities and plenty of information on how to protect oneself from air pollution.

During the event, many curious school students surrounded “ask-theexpert” table with basic yet very pertinent questions such as how do we measure air pollution, what is the effect of air pollution on our lung function, how can we clean the air, what could they do at an individual level to tackle this problem and many more. The experts on the table were India Alliance Senior Fellow at CSIR Institute of Genomics & Integrative Biology, New Delhi, Dr Anurag Agrawal, Dr Bhargav Krishna from the CEH, Mr Barun Agarwal, Founder, Breathe Easy and Dr Nitish Dogra, Community Activist. Many flocked around the home-made instrument to measure their lung capacity.

This event was preceded by a series of school workshops organized by Happy Hands Foundation, where they used traditional Indian arts, such as puppetry and Patua or scroll art to engage with students about the broader issue of environmental health. Many of the students from these workshops also attended the public event and their art was on display.

Women from the Kathputli colony and young kids from Salam Baalak Trust prepared a puppet show and a street theater piece, respectively,

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around air pollution, which they performed every hour during the event.

Researchers and health communication experts from PHFI took active part in preparing the script of these performances along with the performers to ensure accurate health information was disseminated through these acts. After every presentation, the performers also shared their views and personal stories about how air pollution impacts their lives and what they plan to do to alleviate this problem in their communities.

Prior to this event, researchers from PHFI also held environmental health sensitisation workshops at St Stephen’s college and IIIT Delhi, where they debated and discussed various environmental issues impacting human health and deliberated on solutions that would require both innovative technologies and social change.

The aim of the event and the workshops was not limited to increasing awareness on air pollution and environmental health issues but it also explored innovative ways in which important health research and information can be shared and discussed with the public.

Voices for Health is an effort aimed at engaging people and communities to better understand public health and to educate them about key determinants of emergent heath issues. This initiative is planned as a series of public engagement events that will bring together biomedical researchers with policy makers, social scientists, health workers, media and other stakeholders to talk about important health issues. Each event will focus on a public health topic of contemporary interest. The series will aim to demystify science and myths, disseminate latest health research and share perspectives of experts and people. The series has so far explored antibiotic resistance, cancer, mental health and environmental health issues in different cities.

INDIA ALLIANCE STAFF CORNER

Dr Srikrishna Sulgodu Ramachandra

PROGRAMME MANAGER, INDIA ALLIANCE

What is your background?

I come from a town by the name Sagar in Shimoga district of Karnataka state and still regularly visit that place. Since past nine odd years or so, I have been living in Hyderabad and I feel I am now a Hyderabadi in many aspects. It is a great place to live and work. I am very happy with this place and I love the rich blend of the old Nawabi culture (the old city of Hyderabad) with that of the modern culture (the new city of Hyderabad). Although it has the usual drawbacks of any modern city across the globe, in terms of traffic, pollution, etc., I would still strongly recommend Hyderabad for any person who is looking for a place to settle down - for its moderate, tropical weather, affordable cost of living, good livelihood opportunities, vibrant culture and tradition, friendly and helpful people.

I received my MBBS degree from Sri Devraj Urs Medical College, Kolar, MD in Community Medicine from St. Johns Medical College, Bangalore and MPH - International Health and Development from Tulane University, New Orleans. I have always enjoyed working in the area of public health and have worked at various levels and in different capacities. My initial experiential learning on implementation aspects of Public Health have been at UNICEF, where I served on the areas strengthening Routine Immunization and Pulse Polio. My learning in the areas of monitoring and evaluation have been under the Bill and Melinda Gates Foundation (BMGF) funded AVAHAN programme, wherein I have served at different positions. I have gained my programme management skills, training and teaching skills during my service at Public Health Foundation of India (PHFI), wherein I had the opportunity to get involved in academic teaching, training, curriculum development, conducting research on various current public health problems of national and international importance, project and programme management and much more. At PHFI, I was able to enrich my knowledge and hone my skills under the mentorship and guidance of several public health leaders. I have worked in the areas of Health Systems, HIV / AIDS, Tobacco Control, Maternal and Child Health, Disability and Development and Disaster Preparedness.

How have your first six months been and what to do you look forward to at the India Alliance?

which is very efficient and thoroughly professional and more importantly, very supportive and friendly.

Till now, in my career, I consider having had a rich experience of conducting research, teaching, training, programme implementation, submitting research proposals and writing manuscripts, which is one side of the coin. Here at the India Alliance, I am getting to know the other side of the coin - which is the Funder's Perspective: Grants / Fellowships management processes, Fellowship administration, policy and guidelines development in relation to the same. At the India Alliance, I look forward to productively contribute and be a part of the existing and newer initiatives of the organisation, help in building stronger relationships, newer collaborative initiatives and be a strong support to the existing grants, finance and operations team.

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

A family and a full time job, definitely keeps one busy, because of which there is not much time left to enjoy doing other things, except enjoying what one does on a regular basis. Whenever I get a chance, I enjoy gardening and farming, photography and watching movies.

What are some subjects that interest you, that you like to talk about?

Usually paradoxical and controversial topics interests me, for instance if we take the example of tobacco control as a major public health challenge: on one side the health department talks of controlling all forms of tobacco usage and on the other side, there are Government departments which does research on high yield varieties of tobacco crops, subsidies for tobacco crops and so on. Similarly, in the area of road safety for instance, on one side, we talk of reducing air pollution, reducing the number of vehicles on the road and on the other side, in the name of development or status, everyone wants to own a vehicle and no one is interested in the betterment of public transport systems.

These are just a couple of examples and there are many more like these.

Who inspires you (living or dead)?​

My first six months here have been a great deal of learning - a state of the art fellowships / grants administration and management system that is run and managed by a lean team

Mostly, self inspired and on certain aspects my father is my inspiration.

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EXTERNAL EVENTS

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Looking back at 2016 in pictures

Please send your feedback, suggestions and contributions to public.engagement@wellcomedbt.org

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