News & Views Issue 21 May 2018
EDITORIAL India Alliance has a new logo and website address, www.indiaalliance.org, which highlights both our identity as an independent public charity registered in India and our funders Wellcome, UK and DBT, India. This change coincides with India Alliance turning 10 this year and our move towards the next phase of the program. This new identity was unveiled by Prof. K VijayRaghavan at the recently held India Alliance Annual Fellows’ Meeting in Delhi, 17-19 May. This May issue of the India Alliance newsletter includes our Fellowship announcements, recently published research of our Fellows and updates on our new initiatives aimed at enhancing India’s research ecosystems. At the outset, our congratulations to Intermediate Fellows, Dr. Mahak Sharma (IISER Mohali) and Dr. Prerna Sharma (IISc, Bengaluru) for receiving INSA Young Scientist Award. We would also like to extend our heartiest felicitations to Margadarshi Fellow, Prof. Anura Kurpad (St. John’s Research Institute, Bengaluru) for getting elected as the Fellow of the Royal College of Physicians, London. Next call for applications for the Early Career Fellowships in Basic Biomedical Research will be launched on 2 July 2018 and for Senior and Intermediate Fellowships in Basic Biomedical Research on 27 June 2018. Read more about these schemes in this issue. Check India Alliance website for regular updates on our various funding schemes. In the Research Highlights section, we bring to you recently published research of the following India Alliance Fellows. Dr. Abhijit Majumder and his team at IIT Bombay, provide novel insights into cell-cell mechanical interactions that can be employed in tissue engineering. Dr. Kavita Babu and her team at IISER Mohali, in a series of research papers, provide new insights into how neuronal genes regulate locomotion and how genes and environment control an organism’s exploration of its environment using a worm model. Using a primate model, Dr. Supratim Ray and colleagues, provide new insights about the generation of gamma rhythm in the brain as well as processing of color along the visual pathway. Unregulated activation of immune cells can lead to inflammation associated with several diseases, including cancer and autoimmune disorders. Recently published research from Dr.Amit Tuli’s research group at IMTECH Chandigarh, show how the activation of immune cells against pathogenic stimuli hinges on an evolutionarily conserved cellular protein. Correlation of this protein to the aforementioned diseases would need to be further investigated. Chromosomes change their address in response to their environment, shows Dr. Kundan Sengupta’s recently published study. These observations and further research using his approach can provide important clues into how aberrant signals perceived by cells within a tissue are likely to convert normal cells to cancer cells. Dr. Paulomi Sanghavi and Prof. Roop Mallik, propose models to explain the activity of opposing molecular motors that help transport cargo inside a cell.
Government of India report on the causes of death country revealed that the deaths in rural India due to communicable diseases (41 percent) were similar to those due to non-communicable diseases, such as stroke, diabetes etc. (40 percent). Intermediate Fellow, Dr. Yogeshwar Kalkonde writes in India Development Review about the urgent need for preventive programs as well as developing new human resources, technology, healthcare delivery mechanisms and financial resources to tackle NCDs in rural areas. You can read this opinion piece in this newsletter. India Alliance Fellowship program is unique in the way that it allows any scientist wishing to carry out biomedical research in India, irrespective of age and nationality, to apply to any of its funding schemes. One such researcher is Dr. Benedict Weobong, who is a national of Ghana, Africa, and an India Alliance Intermediate Fellow currently working at Sangath, Goa. We feature his interview in the India Alliance Fellow in Spotlight section where he talks about his research focused on drinking behavior among youth in India and the need for promoting mental health research specially in countries like India and Ghana. India Alliance is pleased to announce the launch of the India Alliance gateway on Wellcome Open Research. As part of its commitment to open research policy, the India Alliance has teamed up with Wellcome Open Research to enable immediate publication of manuscripts of India Alliance-funded researchers. The India Alliance, with support from European Molecular Biology Organization (EMBO) organized EMBO Research Leadership course for researchers in India to train them in leadership and management skills that are critical for a successful career in science. Two courses were held from 19-22 March 2018 in New Delhi and 26-29 March 2018 in Hyderabad. Read more about the workshop and the trainer’s experience of organizing first leadership course in India. In the Public Engagement section, read about the recently held Art and Science program, The Undivided Mind: Edition III, at Khoj International Association, New Delhi. Also find in this section, latest offering from the Life of Science team in the Women in Science series supported by the India Alliance. As part of the recently launched program, India Research Management Initiative (IRMI), a sharing session was held at IISER Pune on 19 April 2018, to discuss enablers and challenges of research management in India with a group research managers and scientists from different institutions. We are currently accepting applications for the Africa-India Mobility Fund (AIMF), an initiative of India Alliance and African Academy of Sciences to promote cross-learning and collaboration between India and African biomedical researchers. More information on this funding has been included in this issue. As always, a massive thank you to all those who have contributed to this newsletter. Finally, the India Alliance Annual Report 2017-18 was released at the Annual Fellows’ Meeting by Dr. Renu Swarup, Secretary, DBT. Report can be downloaded here. Special thanks to Shruti Thapliyal, PhD student at IA Fellow Dr. Kavita Babu’s lab, for sharing a confocal microscopy image of the nematode worm, C. elegans, expressing a neuronal protein CASY-1, labelled green for the cover.
Research Matters covers Dr. Farah Ishtiaq’s recent study that
reveals that high intensity of blood parasites such as those that cause malaria, destroy red blood cells and reduces the amount of haemoglobin in the migrant birds in the Himalayas. They also observed that the parasite load was higher in these birds in winter season, suggesting that temperature plays an important role in regulating transmission of parasites.
As always, it’s helpful to receive your valuable comments and suggestions for the newsletter so make sure you keep them coming. Find archives of our past newsletters here. Sarah Hyder Iqbal, PhD Public Engagement Officer Wellcome Trust/DBT India Alliance
May 2018
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CONTENT 4
India Alliance Fellowships
5
New India Alliance Fellows
10 Fellows’ Research Highlights 15 India Alliance Fellow in Spotlight
Interview with Intermediate Fellow, Dr. Benedict Weobong Sangath, Goa
17 Rural India faces epidemic of Non-communicable diseases
Opinion piece by Intermediate Fellow, Dr. Yogeshwar Kalkonde, SEARCH, Gadchiroli
19 India Alliance training workshops * EMBO Research Leadership course *Research Methodology
21
Public Engagement *Actor and Doctor – Public Health Theatre Festival * Women in Science
23 New initiatives * India Alliance Gateway on Wellcome Open Research * India Research Management Initiative * Africa-India Mobility Fund
26 Other announcements India Alliance Annual Report
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INDIA ALLIANCE
FELLOWSHIPS Early Career Fellowships in Basic Biomedical Research Preliminary application deadline : 31 July 2018 India Alliance will be accepting applications for its Early Career Fellowships in Basic Biomedical Research from 2 July 2018. This is a mentored Fellowship programme that provides a unique opportunity for promising postdoctoral researchers to carry out high-quality biomedical research in India towards building an independent research career.
• • •
Competitive personal support Generous research funds Funding to work overseas for up to 2 years and develop international collaborations
Essentials on the preliminary application Outline (750 words) of a research proposal that seeks to answer an original biomedical research question A Fellowship Supervisor who would guide the applicant in the proposed research and a letter of support to this end; the proposed research is expected to complement and benefit from the Fellowship Supervisor’s research interests and expertise An additional letter of recommendation
Eligibility Applicant must be in the final year of PhD or have no more than four years of post-PhD research experience from the date of PhD viva to the invited full application submission deadline (tentatively in October 2018 for the current round of competition); due consideration will be given to justified career breaks Applicant may have/be pursuing PhD in any discipline of science There are no restrictions based on age or nationality Applicant need not be resident in India while applying, but should be aspiring to launch an independent research career in India Applicant must choose a not-for-profit host institution in India that will administer the Fellowship for the full duration (5 years) of the award in line with India Alliance conditions and policies Applicant may or may not have a faculty position
Preliminary application forms will be available from 02 July, 2018, 09.00 am IST on the India Alliance online application System (IASys). Preliminary applications due by 31 July, 2018, 12 noon IST. Please visit India Alliance website for further information on eligibility, remit, provisions, and the application process. Queries may be addressed to info@indiaalliance.org
Remit Full spectrum of biomedical science from fundamental molecular and cellular studies through Clinical and Public Health research** Interdisciplinary projects are welcome
**We encourage Clinicians and Public Health researchers to apply in the separate Clinical and Public Health Research Fellowship competition which would be announced later.
Provisions: The 5-year Fellowship typically provides:
Senior and Intermediate Fellowships in Biomedical Research Preliminary application deadline : 25 July 2018 The India Alliance will be accepting applications for its Senior and Intermediate Fellowship scheme from 27 June 2018. 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 also welcome.
been successful in building a track record of pursuing a cutting edge research and wish to establish their own independent research program in India. Provisions
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.
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 complete duration of the award • A sponsor at the Host Institution, who can guarantee space and resources for the duration of the award Application forms will be available on the India Alliance online application System (IASys) on 27 June 2018, 09.00 am IST. Please visit India Alliance website for further information on these Fellowships. Queries may be addressed to info@indiaalliance.org
**We encourage Clinicians and Public Health researchers to apply in the separate Clinical and Public Health Research Fellowship competition which would be announced later.
Intermediate Fellowship: For postdoctoral researchers who have
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NEW
INDIA ALLIANCE FELLOWS Determining the role of pancreatic alpha-cell autophagy in intra-cellular glucagon turnover and its modulation as an antidiabetic therapy
INTERMEDIATE FELLOWS 2017 Basic Biomedical Research Fellowships
Bacterial evolution in hostassociated communities Dr. Deepa Agashe
Dr. Rohit Anthony Sinha
National Centre for Biological Sciences (NCBSTIFR), Bengaluru
Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow
Bacteria typically live within complex communities composed of many species, that are in turn associated with other organisms. For instance, recent research suggests that most animals harbour (and depend upon) the millions of bacteria that they carry. What is the impact of this complexity on bacterial evolution? Specifically, if the host changes its diet, how does the gut bacterial community change? Such scenarios of dietary change are likely to be very common in many animals, including humans. If some gut bacteria cannot live in the new nutritional environment in the host’s gut, they might go extinct, or they might acquire mutations that turn out to be beneficial. Ultimately, some of these changes in the bacterial community may also improve the host’s ability to survive on the new food. We plan to test these ideas using flour beetles, which are common pests of cereal flours and derive a survival advantage from their gut microbes. In the laboratory, we will allow beetles to adapt to new flours on which they typically have high mortality, and then analyse how their gut bacterial communities change across evolutionary time. Our work will thus help understand how dietary shifts in animals affect the evolution of their gut bacteria.
My India Alliance-funded research is primarily focused on understanding the role of lysosomes and autophagy in the process of hormone secretion. Glucagon is glycoprotein hormone secreted by pancreatic alpha(Îą)-cells and plays a significant role in the pathogenesis of both Type I and Type II diabetes mellitus (DM). Under normal physiological conditions, glucagon secretion is increased and insulin secretion is decreased during starvation to counteract hypoglycaemia in humans via increasing hepatic glucose output. However, in diabetes, glucagon secretion becomes insensitive to both high glucose and insulin inhibition, and contributes to hyperglycaemia. In my current research, I attempt to understand and modulate a cellular degradative process known as autophagy to reduce the amount of glucagon content inside the pancreatic alpha-cells which secrete them. We believe that the results obtained from this study would benefit future diabetes research and treatment.
Figure: Possible effects of host diet shift on the gut microbiome. The host has low initial fitness on the new diet. As it adapts to the new diet, the microbiome may show (A) Immediate ecological change in composition (B) Longer term evolutionary change or (C) Both ecological and evolutionary changes
Figure: Mitophagy as visualized in TEM with a damaged mitochondrial (red) seen engulfed by an electron dense double membrane structure.
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NEW INDIA ALLIANCE FELLOWS
Post-transcriptional regulators of aging and dietary/caloric restriction
EARLY CAREER FELLOWS 2017 Basic Biomedical Research Fellowships
Understanding the import of sugar molecules by pathogenic bacteria
Dr. Geetanjali Chawla Regional Centre for Biotechnology (RCB), Faridabad
Dr. Parveen Goyal Institute for Stem Cell Biology and Regenerative Medicine (InStem), Bengaluru
In this project, we will assess the role of age- and dietary restriction-modulated small non-coding RNAs termed microRNAs in enhancement of lifespan and reducing risk factors associated with aging. Understanding how conserved microRNA mediated networks operate to affect the overall lifespan of an organism will illuminate the basic principles underlying the aging process that can be applied to the development of RNA based therapeutic strategies that would mediate their broad-spectrum health-improvement by not only triggering the same molecular pathways that are elicited by long term dietary restriction, but also, counteract late onset diseases.
Pathogenic bacteria are very clever in using host derived molecules, not only for their growth, but also eluding the host defense mechanism and cause diseases. Sialic acid, a nine carbon sugar, is such a molecule and is found abundantly in humans. Some bacteria can import this sialic acid and utilize as a carbon source for energy production or modify their own outer surface. Sialic acid decorated bacteria will be recognized as “self� by human immune cells and will thrive well. Thus uptake of sialic acid can remarkably increase survival of pathogenic bacteria inside a host.
My laboratory will utilize genetic, molecular, proteomic and metabolomics approaches to:
To import sialic acid, bacteria use specific classes of proteins present in their membranes. I focus on such a class of the membrane proteins which help bacteria in scavenging sialic acid. The main goal is to get a detailed structure of such membrane protein complexes and use that for drug screening. The work can result in new drugs for better treatment of diseases caused by the bacteria.
1. Determine how dietary restriction (DR) and age-modulated microRNAs influence lifespan. 2. Test the ability of DR and age-modulated microRNAs to lower risk factors associated with aging. 3. Identify and characterize downstream targets of DR and agemodulated microRNAs. At the completion of these studies we expect to identify conserved microRNAs that can mimic the anti-aging effects of dietary restriction in animals that are fed a normal diet.
Figure Legend: Sialic acid transport in bacteria: (A) Bacteria can import sialic acid through proteins present in their membrane. Once internalized, sialic acid can either be used to generate energy, or as a decoration for the bacterial outer surface to evade host immune system. (B) By blocking the membrane transport protein, bacteria will fail to use sialic acid for energy generation or surviving the host defense mechanism. This decreases overall survival fitness of such bacteria inside a host.
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NEW INDIA ALLIANCE FELLOWS
Receptor tyrosine kinase signaling in skeletal muscle development, regeneration and disease
EARLY CAREER FELLOW 2017 Clinical and Public Health Research
Evaluating causal relationship between regional body fat distribution and lipid profile in Indian population
Dr. Masum Saini
Regional Centre for Biotechnology (RCB), Faridabad
Dr. Gagandeep Kaur Walia Public Health Foundation of India, Gurgaon
Receptor tyrosine kinases (RTKs) comprise a family of cell surface receptors that mediate signaling cascades critical to cellular processes such as survival, proliferation, differentiation and migration. These processes in turn are essential for organ morphogenesis, embryonic development and tissue homeostasis. Previous studies have shown that RTKs crucial for developmental morphogenesis are also dysregulated in pathological states. For example the RTKs -FGFR3 and c-KIT play crucial roles during development and mutations in these genes cause the developmental disorders dwarfism and piebaldism. Interestingly, aberrant signaling from these RTKs cause bladder cancer and gastrointestinal stromal tumors respectively. Similarly, signaling through the RTK MET is vital during developmental skeletal myogenesis, and adult muscle regeneration; MET is also known to be dysregulated in Rhabdomyosarcoma, a cancer related to the myogenic lineage. Since, MET signaling is crucial to skeletal muscle development and regeneration, it is important to determine the mechanisms underlying its regulation that have remained largely unexplored. My aim is to understand the specific spatial and temporal regulation of this signaling pathway in skeletal muscle development, regeneration and disease using mouse as in vivo model and myogenic cells as in vitro tool. The proposed work will provide important insights into regulation of skeletal muscle development and regeneration, which could potentially aid therapy in muscle diseases such as Duchenne muscular dystrophy and muscle atrophy during ageing.
The aim of the proposed study is to examine whether regional body fat distribution is causally associated with lipid levels in Indian population. We will first identify the genetic variants associated with adiposity and lipid traits to derive instrument variables based on allelic scores and then use them as proxy for exposures and outcomes in examining the causal pathways using bi-directional Mendelian Randomization approach. We will be generating genome-wide data on intensively phenotyped “CARRS cohort study” participants using a recent GWAS chip named Global Screening Array (~640,000 markers) to identify India specific markers. We will also utilize the available cardio-metabochip data (~200,000 markers related to cardiometabolic traits) on well-phenotyped data from “Indian Migration Study” in order to validate the loci of interest. Therefore, this will collectively help in deriving allele scores to be used as genetic proxies for the traits to be examined on the causal pathway i.e. body fat distribution (exposure) and lipid levels (outcome). The findings from the proposed study will provide evidence for the causality between increased regional adiposity and raised levels of lipids. This will help in formulating public health interventions and clinical management of the high risk patients and will address the growing burden of cardiometabolic disorders.
Figure : Confocal image showing alveolar rhabdomyosarcoma cells labeled by immunofluorescence for MET (red), phalloidin (green) marking the actin filaments and DAPI (blue) staining the nuclei.
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NEW INDIA ALLIANCE FELLOWS
RESEARCH TRAINING FELLOWS 2017 Clinical and Public Health Research points towards geographical differences in the distribution of the disease in the Indian subcontinent itself which indirectly gives a clue to the possibility of a genetic association.
Understanding phenotypes in Moya moya disease: An imaging genomics approach
We plan to conduct an imaging genomics study to explore the genetics of MMD in south Indian population
Dr. Arun K Sree Chitra Tirunal Institute for Medical Sciences and Technology & Rajiv Gandhi Centre for Biotechnology, Trivandrum Moyamoya disease (MMD) is a rare chronic cerebrovascular disorder characterized by progressive bilateral occlusion of the supra-clinoid internal carotid artery (ICA) and its main branches. This is associated with the development of fine collateral networks, adjacent to the site of occlusion in the deep areas of the brain. Epidemiological data have shown strong regional differences with a high occurrence in Asian countries primarily Japan, China and Korea. An incidence of approximately 1 per 100 000 has been reported in Japan. The incidence in nonAsian countries, frequently cited in the literature is 0.1 per 100 000. Recently genome-wide linkage analysis and exome analysis studies identified the ring finger protein 213 gene (RNF213) on 17q25.3 as the strongest susceptibility gene for MMD in East Asian population. Mutational analysis studies revealed a single missense mutation in RNF213 (p.R4810K). This mutation was detected in 90% of Japanese, 79% of Korean and 23% of Chinese MMD cases. It strongly increased the risk to develop MMD with an OR of 338.9 (p =10-100) in Japanese, 135.6 (p = 10-25) in Korean and 14 in Chinese populations respectively. The mutated allele occurs in 95.1% of familial MMD cases and 79.2% of sporadic MMD cases. The homozygous mutation, was associated with an earlier onset and a more severe disease course suggesting it a potential biomarker for predicting prognosis. In addition, MMD presents with a characteristic angiographic picture which involves the bilateral stenosis or occlusion at the terminal portion of the ICA and at the proximal portion of the anterior and middle cerebral arteries, abnormal vascular network seen in the vicinity of the arterial occlusion. Moyamoya like angiographic picture occurs in intracranial atherosclerotic disease, sickle cell disease and intracranial arterial dissection which may confuse the diagnosis and management. Vessel wall imaging (VW-MR) is a novel imaging technique which helps to differentiate the various aetiologies of distal intracranial arterial occlusion which demonstrates eccentric arterial wall thickening in intracranial atherosclerotic disease while smooth, homogeneous, concentric arterial wall thickening and enhancement in vasculitic disorders. However, VW-MR imaging studies with MMD found a lack of arterial wall thickening and enhancement. Interestingly, clustering of patients with MMD has been observed particularly from the south eastern region of Indian subcontinent which
Figure (left): Axial flair sequence showing chronic infarcts in the left MCA territory with volume loss and gliosis, in addition “Ivy sign� noted (arrow) in the left temporo-parietal region. Figure (right) Digital subtraction angiography showing significantly attenuated bilateral supraclinoid internal carotid artery, MCA-M1, ACA-A1 with basal collaterals simulating puff of smoke typical of Moya moya disease.
A computer game-based rehabilitation platform for patients with fine and gross motor upper extremity impairments due to stroke Dr. Dorcas B C Gandhi Christian Medical College Ludhiana
We are evaluating the feasibility and efficacy of using a computer game based rehabilitation protocol for stroke patients with upper limb impairments. We aim to focus on the functional abilities of the patients despite their anatomical limitations. To make therapy more engaging, focused and measurable quantitatively the platform we have developed will be useful and will also allow manipulation of various objects used for activities of daily living by the impaired upper extremity. This would make therapy functionally oriented and early independence of patients. Continued on the next page..
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NEW INDIA ALLIANCE FELLOWS
Exploring the role of intracellularly formed sphingosine 1-phosphate (S1P) in mediating the anti-atherogenic effects of adiponectin on endothelial cells Dr. Vinnyfred Vincent
Other ongoing researches in our lab explore the functional aspects of HDL as a better predictor for cardiovascular risk compared to the traditional quantitative approach and the modulation of insulin resistance and HDL quality by adipose tissue in the setting of obesity.
All India Institute of Medical Sciences (AIIMS), New Delhi
Despite recent advances in diagnosis, interventional techniques and pharmacological treatments targeting several risk factors of cardiovascular disorders (CVD), cardiovascular mortality is one of the leading causes of death globally. The pathophysiology of atherosclerosis, which is the hallmark of cardiovascular disorders is not fully elucidated. Research focus of our lab is metabolic derangements associated with obesity and atherosclerosis. Three major anti-atherogenic molecules in circulation are high density lipoprotein (HDL), adiponectin and sphingosine 1phosphate (S1P). Modulation of these molecules individually has not provided clinically relevant anti-atherogenic effects, which shows that the interplay between these molecules may be important in their impact on the development of atherosclerosis. The research funded by India Alliance explores how adiponectin, HDL and S1P provides anti-atherogenic effects on endothelial cells by acting in a sequential manner. Understanding the interplay between these molecules could provide new targets for modulation in order to modify cardiovascular disease risk in susceptible individuals, especially in the setting of obesity.
Figure: Hypothetical pathway explored in the research. AdipoR1: Adiponectin receptor subtype 1, SK1: Sphingosine kinase 1, ABCA1: ATP binding cassette transporter A1, S1P: Sphingosine 1-phosphate, HDL: High density lipoprotein and S1PR1: Sphingosine 1-phosphate receptor subtype 1
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INDIA ALLIANCE FELLOWS’
RESEARCH HIGHLIGHTS
Novel insights into cell-cell mechanical interactions that can be employed in tissue engineering Dr. Abhijit Majumder, Early Career Fellow Indian Institute of Technology (IIT) Bombay
Different parts of our body have different stiffness. While influence of these varied stiffness on our wellbeing is obvious in some situations, such as muscle has to be soft to provide flexibility whereas bone has to be rigid to provide structural integrity, effect of tissue stiffness on cellular behavior is much more widespread. Adherent cells measure the stiffness of their micro-environment by holding and pulling the surrounding materials and respond accordingly. For example, studies with mesenchymal stem cells (MSCs) or “adult” stem cells have shown that they do not divide when grown on soft materials. Substrate stiffness also controls whether a stem cell would become nerve cell or muscle cell or something else. Other than that, tissue stiffness is known to influence metastasis and drug resistance in cancer.
together can make the substrate stiff simply by pulling it in two opposite direction similar to making a flexible rope taut in tug of war. This way, together they can overcome the effect of soft surface. For instance, even though many adherent cells cannot divide when on soft substrate, together they can overcome this effect of soft surface on cell division. Another interesting observation was that they together form a network holding "hand in hand" to provide sufficient support for each other which is lacking on a soft surrounding.
However, most of these observations are made when cells are cultured at sparse keeping them away from each other. This is very different from the situation in our body where cells are much more closely spaced. What happens when cells are so close that pulling by one cell is felt by its neighbor? Our research has found that as we reduce the distance between two cells on soft substrate (such as polyacrylamide gel), they
Reference: Cell density overrides the effect of substrate stiffness on human mesenchymal stem cells’ morphology and proliferation. Balu Venugopal, Pankaj Mogha, Jyotsna Dhawan and Abhijit Majumder. Biomaterials Science. March 2018
The knowledge gained in this research is useful in tissue engineering and discovering newer treatment strategies in addition to enhancing our understanding of how cells work together in our body.
Travelling in reverse – new insights into how genes and environment control an organism’s exploration of its environment Dr. Kavita Babu, Intermediate Fellow Indian Institute of Science Education and Research (IISER) Mohali The human brain has billions of neurons that are interconnected in a complex network. Connection between two neurons is called a ‘synapse’. Many molecules present at the synapse ensure that these connections remain stable. Any dysfunction at the synapse can give rise to a host of neurological disorders such as autism, dementia, addiction etc. Some of these molecules inside the neurons that regulate activation and inhibition of these neurons are called neurotransmitters. Apart from neurotransmitters a set of small peptides (small chain of amino acids) are also known to allow for activation and inhibition of neurons largely via downstream signaling through cell surface proteins called G-protein coupled receptors (GPCRs). These peptides are
called neuropeptides and the functioning of these peptides is still fairly unclear. In our lab, we are interested in studying how these peptides work so as to get a better understanding of the workings of neurons and consequently, our brain. In a recently published study from our group, we used the freeliving soil nematode or worm, Caenorhabditis elegans (C.elegans), to understand how a single neuropeptide, FLP-18, functions through two sets of receptors to inhibit activity in a single neuron. C.elegans have long been used by scientists to study human biology as this organism possesses key biological features, including a nervous system, similar to humans. Continued on next page…
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INDIA ALLIANCE FELLOWS’
RESEARCH HIGHLIGHTS C.elegans, unlike humans who can quickly turn clock-wise or anticlock-wise, travel in reverse when they need to make a turn. These movements are critical for worm’s survival – whether it is to search for food or to move away from potential predators.
Our research shows that the neuropeptide FLP-18, functions through two GPCR receptors, NPR-4 which is functional on the FLP-18 expressing neuron AVA (giving rise to a feedback of activation and inhibition of the same neuron) and NPR-1 which is expressed on a subset of sensory neurons. Through the activity of these two receptors FLP-18 is able to inhibit the activity of the AVA neuron, which in turn allows for the worm to stop making a reversal or backward motion. The absence of either flp-18 or its receptors’ shows increase in the activity of the AVA neuron and a corresponding increase in the length of the reversals in C.
We further show that in the absence of food the worm shows increased levels of FLP-18 and a corresponding decrease in the reversal length. Our hypothesis is that with shorter reversals, worms are able to turn and change directions more quickly in their search for food – they conserve energy under starvation conditions. Our data is illustrated in the published model shown below (Bhardwaj et al., 2018). Reference: FLP-18 Functions through the G-Protein-Coupled Receptors NPR1 and NPR-4 to Modulate Reversal Length in Caenorhabditis elegans. Bhardwaj, A., Thapliyal, S., Dahiya, Y., and Babu, K. The
Journal of Neuroscience. May 2018
elegans.
Role of a calcium-binding neuronal protein in regulating locomotion in a worm model A functional nervous system requires strength from two pillars that form the basis of synaptic transmission; excitation and inhibition. Excitatory signals from presynaptic cells to postsynaptic cells make the latter more likely to fire, while inhibitory signals decrease the probability of firing in the postsynaptic cells. An imbalance in excitatory and inhibitory signaling has been reported to be a factor in the pathogenesis of several neurological disorders like Alzheimer’s disease, autism spectrum disorders and epileptic seizures. The neuromuscular junction (NMJ) of the tiny nematode worm, C. elegans receives synaptic inputs from both excitatory and inhibitory motor neurons, thus making it an excellent system to study the balance between excitation and inhibition. We have characterized an isoform specific role for a calciumbinding protein, Calsyntenin, CASY-1 in maintaining this balance at the NMJ. The shorter isoforms of CASY-1; CASY-1B and C contain the conserved C-terminus of mammalian Calsyntenins. We show that the shorter isoforms regulate the release of the inhibitory neurotransmitter GABA from GABAergic motor neurons. CASY-1B/C interact with the motor protein UNC104/KIF1A and allow for the normal trafficking of GABA synaptic vesicles, thus modulating GABA release at the NMJ (Thapliyal et al., 2018b). GABA acts as one of the major inhibitory neurotransmitters in both vertebrate and invertebrate nervous system.
In light of this work, we hypothesize that in the absence of casy1, the balance between excitation and inhibition at the NMJ is disturbed, resulting in altered locomotary behavior. Restoring this balance by expressing CASY-1B/C in GABAergic motor neurons or CASY-1A in sensory neurons completely restores the movement defects seen in casy-1 mutants. Our study illustrates a novel role for C. elegans ortholog of mammalian Calsyntenins in regulating excitation-inhibition balance at the NMJ (see illustration). Mammalian Calsyntenins have been implicated in the pathogenesis of several neurological disorders. Thus, future investigations in this area could enhance our understanding about pathophysiological mechanisms that trigger Calsyntenin related brain disorders. References Analysis of NPR-1 reveals a circuit mechanism for behavioral quiescence in C. elegans. Choi, S., Chatzigeorgiou, M., Taylor, K.P., Schafer, W.R., and Kaplan, J.M. Neuron. 2013 Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release. Choi, S., Taylor, K.P., Chatzigeorgiou, M., Hu, Z., Schafer, W.R., and Kaplan, J.M. PLoS genetics 2015. Regulation of Glutamate Signaling in the Sensorimotor Circuit by CASY-1A/Calsyntenin in Caenorhabditis elegans. Thapliyal, S., Ravindranath, S., and Babu, K. (2018a). Genetics . 2018a
We also show that the longer CASY-1A isoform, which contains all the conserved domains of mammalian Calsyntenins, modulates the activity of sensory neurons by regulating stable release of the neurotransmitter, Glutamate (Thapliyal et al., 2018a). Glutamate release in turn has been shown to maintain normal release of the excitatory neurotransmitter acetylcholine at the NMJ (Choi et al., 2013; Choi et al., 2015).
The C-terminal of CASY-1/Calsyntenin regulates GABAergic synaptic transmission at the Caenorhabditis elegans neuromuscular junction. Thapliyal, S., Vasudevan, A., Dong, Y., Bai, J., Koushika, S.P., and Babu, K. PLoS genetics. 2018b
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INDIA ALLIANCE FELLOWS’
RESEARCH HIGHLIGHTS
New insights into color processing in the primate visual cortex Dr. Supratim Ray, Intermediate Fellow Indian Institute of Science (IISc), Bengaluru
To understand brain function, electrical activity can be recorded using a variety of techniques, such as using microelectrodes in monkeys that provide information at a very local scale (one or a few neurons), to diffuse population measures such as electroencephalography (EEG) in humans that provide information at a much larger scale (millions of neurons). At such scales, brain signals often show oscillations at different frequencies, whose magnitude or frequency may depend on the cognitive state. Signals recorded from the brain often show rhythmic patterns at different frequencies. One such rhythm is called “gamma”, which occurs between 30-80 Hz, and has been linked with high-level cognition such as meditation and attention. Interestingly, gamma can also be induced in the visual cortex (part of the brain that processes visual information) by viewing certain stimuli, even when no other task is involved. One stimulus that induces strong gamma is called a grating, which consists of black-and-white alternating stripes, but whether natural stimuli (which are typically not black-and-white) also produce strong gamma is not well understood.
In our lab, we showed monkeys a variety of natural stimuli while recording gamma rhythm from their primary visual cortex. Surprisingly, we found that whenever the monkeys saw a red colored object, their brain generated an intensely large gamma wave, almost ~10-fold larger than grating-induced gamma. The magnitude of gamma was dependent only on the purity of the color, but largely invariant to overall brightness. This gamma appeared to be correlated with a specific type of color computation done in the brain. These results provide new insights about the generation of gamma rhythm as well as processing of color along the visual pathway. Reference: Long-wavelength (reddish) hues induce unusually large gamma oscillations in the primate primary visual cortex. Vinay Shirhatti and Supratim Ray (2018). PNAS, April 9, 2018
Banner image credit: Wellcome Images
Activation of immune cells against pathogenic stimuli hinges on an evolutionarily conserved cellular protein Dr. Amit Tuli, Intermediate Fellow
CSIR-Institute of Microbial Technology (IMTECH), Chandigarh A functional immune system enables our vulnerable bodies to mingle freely with the environment teeming with billions of microbes. Nothing supports this statement better than diseases resulting in severe immunodeficiency where even a brief exposure to “normal” surroundings can be life threatening. Crucial defenders in our immune system army, macrophages (derived from the Greek word meaning “large eaters”) are cells that engulf and degrade pathogens while alerting the other sentinels about the presence of foreign pathogens. Although required for proper immune function, unregulated activation of macrophages is responsible for inflammation associated with several diseases, including cancer and autoimmune disorders.
activated macrophages to clear away the pathogen. In agreement with this, macrophages lacking Arl11 expression, fail to efficiently internalize, and degrade pathogenic bacteria. Interestingly, we found that merely increasing Arl11 levels was sufficient to induce macrophage activation in the absence of pathogenic stimuli. This suggests Arl11 expression is tightly controlled to prevent unnecessary macrophage activation. Since macrophage activation is not only crucial for defense against pathogens, but also leads to inflammation that damages the uninfected normal tissues. Therefore, it will be highly relevant to further investigate whether Arl11 expression is correlated with inflammatory conditions such as autoimmune disorders, atherosclerosis, and obesity.
In a recent study, we have uncovered a molecular player important for macrophage function – Arl11, a protein that activates macrophages in response to pathogenic stimuli (Arya SB et al., Journal of Biological Chemistry, 2018). Our study provides the first clue to the cellular function of Arl11, an evolutionarily conserved protein that has remained functionally uncharacterized till date. Our research findings show that Arl11 expression is upregulated in macrophages stimulated with pathogen-associated molecules, such as LPS. Arl11, in turn initiates a cascade of signaling events, resulting in an “effector” response by the
Reference: Arl11 regulates lipopolysacchride-stimulated macrophage activation by promoting MAPK signaling. Subhash B. Arya, Gaurav Kumar, Harmeet Kaur, Amandeep Kaur, and Amit Tuli. Journal of Biological Chemistry. April 2018
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Media Report: Scientists uncover a piece in the puzzle of macrophage activation; could help with understanding functioning of the immune system. FirstPost. May 23 2017
INDIA ALLIANCE FELLOWS’
RESEARCH HIGHLIGHTS Chromosomes change their address in response to their environment Dr. Kundan Sengupta, Intermediate Fellow
Indian Institute of Science Education and Research (IISER), Pune The human body has many different types of cells which can be distinguished from one another by their shape and stiffness. The brain is a very soft tissue; while kidney, liver and intestine are of intermediate stiffness and bones are very stiff. The stiffness of the tissue is a combined property of cells and their interaction with the environment. Most remarkably, changes in the stiffness of the environment relays information into the nucleus directing gene expression to cater to the functions of that tissue. The nucleus houses DNA as chromosomes, that are organized as specific territories in the 3-dimensional space of the nucleus. Chromosomes find their address inside the nucleus reproducibly across cell division cycles. Chromosomes containing more genes (gene-rich) are located in the nuclear interior, while chromosomes with less genes (gene-poor) are closer to the edge of the nucleus. Does the stiffness of the tissue affect the organization of chromosomes in the nucleus and does this in turn affect gene expression? In the lab, cells are typically grown on stiff plastic dishes or glass coverslips. To assess the impact of substrate stiffness on the genome, we exposed colon cancer cells to two extremes of stiffness - soft gels and stiffer glass coverslips. Interestingly, we found that gene-poor chromosomes moved from their otherwise peripheral position into the nuclear interior simply by exposing cells to softer matrices for ~90 minutes. Chromosome locations responded very quickly to changes in stiffness of the environment, as they returned to their original locales in ~90 min, in cells transferred back to glass. These results highlight the remarkable plasticity of our genomes and its rapid response to changes in the
mechanical properties of its external milieu. Further, we discovered that a protein - Emerin, which resides in the inner nuclear membrane undergoes a modification (phosphorylation) in cells exposed to soft gels and serves as a key relay signal to activate changes in chromosome locations. The relative location of chromosome territories determines the type and quantity of gene expression in the form of RNA – a chemical cousin of DNA. Our studies show that RNA levels are directly altered by the interaction of a cell with its environment, which is cell type specific. Our studies require further investigation of tissue type and cell type specific location and expression of chromosomes in response to changes in the stiffness of their external environment. This approach will provide tantalizing clues of how aberrant signals perceived by cells within a tissue are likely to convert seemingly normal cells to cancer cells. Reference : Emerin modulates spatial organization of chromosome territories in cells on softer matrices. Pradhan R, Ranade D and Sengupta K. Nucleic Acids Research. April 2018 Banner image credit: Dr. Kundan Sengupta. Description: Cells exposed to softer gels or matrices begin to spread as shown by cells producing extensions or cable like projections (green). This shows how changes in the properties i.e stiffness of the external environment affects cell shapes, which in turn affects locations of chromosomes in the nucleus.
Coin tossing explains the activity of opposing molecular motors that transport cargo inside a cell Dr. Paulomi Sanghavi, Early Career Fellow Corresponding author : Prof. Roop Mallik, Senior Fellow Tata Institute of Fundamental Research (TIFR), Mumbai Microtubules are hollow tubes made up of proteins that are part of the cell's overall skeleton and are responsible for maintaining the cell shape, transporting material inside the cell and cell division. Microtubules are used by eukaryotic cells to segregate their chromosomes during cell division. Microtubule motors Kinesin and Dynein are required for localization of many different organelles inside the cell. Most Kinesins transport cargoes towards microtubule plus-ends towards cell periphery while Dynein is a minus-end motor, which transports molecules towards cell center. How opposite polarity motors present on a cargo work together to achieve bidirectional transport is hotly debated. Some reports suggest that opposite motors are engaged in a Tug-of-War scenario where both motors pull against each other. Thus, the direction of motion is dictated by the winning motor. On the contrary, another model proposes that motor activity is highly coordinated and only one motor is kept active at one given time. In this study, we addressed how back and forth motion of early phagosomes is achieved by Kinesin and Dynein motors. Interestingly, we find that activity of Kinesin and Dynein motors on early phagosome is stochastic. Unlike the proposed models, we
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showed that inactivating one set of motors does not affect the activity of the opposite motor suggesting that both Kinesin and Dynein function independently of each other. Using mathematical modeling, we also showed that the choice between Kinesin and Dynein could be explained by tossing a hypothetical fair coin. Thus, our model provides a conceptual framework for understanding bidirectional transport. We believe that the choice between Kinesin and Dynein motors can be affected by regulatory proteins or lipids or other molecules, which bias the coin hence allowing one motor to predominate and drive cargo transport to their respective sub-cellular sites. Reference: Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes. Paulomi Sanghavi, Ashwin D’Souza, Ashim Rai, Arpan Rai, Ranjith Padinhatheeri, Roop Mallik. Current Biology. April 2018
INDIA ALLIANCE FELLOWS’
RESEARCH HIGHLIGHTS Is malaria sucking up oxygen in the Himalayan birds?
By Paramananda Barman Mountains are harsh, hostile terrains where life does not come easy. But, there are a few plants and animals, including humans (think of the Sherpas of Nepal) that call these lofty peaks home, braving the biting cold! At such heights, oxygen—our essential requirement to live—is scarce too, resulting in hypoxia—a condition where body tissues are starved of oxygen. Hence, these plants and animals have evolved specific adaptations that help them thrive. For example, the Tibetans and Sherpas are bestowed with 'super athlete' gene, which regulates the production of haemoglobin to help them breathe in air that has reduced oxygen. Birds in the mountains have a greater misery. They are prone to infections by various blood parasites that attack their blood cells, reduce the concentration of haemoglobin and the oxygen-carrying capacity of their blood. So how do they deal with such infections? A Wellcome Trust/DBT India Alliance funded new study by Dr. Farah Ishtiaq and her team from the Centre for Ecological Sciences, Indian Institute of Sciences, Bengaluru, have explored answers to this vital question. The study was conducted on 18 species of passerine birds (birds belonging to the order Passeriformes) across seven elevations in the western Himalayas during the breeding season (April-May) and the non-breeding seasons (January- March).
black flies transmit Leucocytozoon. The sexual phase of the parasite takes place in the vector species, and the asexual phase happens in the birds”, explains Dr. Ishtiaq. The study reveals that high intensity of these blood parasites destroy the red blood cells and reduce the amount of haemoglobin in the migrant birds. When a bird is infected with more than one type of the parasite, it could turn lethal. The researchers found that Leucocytozoon was present in most of the samples, with 40% prevalence, followed by Haemoproteus and Plasmodium. They also found that the probability of infection by Plasmodium was high in the plains and the risk of infection by Leucocytozoon increased with the height. An interesting finding of the study was that the researchers observed an increased parasite load, a measure of the number and virulence of the parasites in a host, in the non-breeding (winter) season. “This is in stark contrast with previous studies
conducted in temperate regions where the intensity of infection was reported to be higher during the breeding season. This contrast for Himalayan birds could be either due to cold weather or poor food availability,” explains Dr. Ishtiaq. They also observed
The birds in the western Himalayas follow two migration strategies. A few of them stay in the higher elevations all year. The others, called ‘elevational migrants’, move to breeding grounds in higher elevations only during the summer and return to the plains during the harsh winter. It is during this time that they are at a higher risk of contracting infections since the birds in the lowlands are loaded with blood parasites, which could compromise the capacity to regulate haemoglobin and cope with hypoxia.
“An earlier study on Himalayan birds showed that they modulate haemoglobin in the blood to increase its oxygen-carrying capacity. In this study, we wanted to understand how these birds deal with the increased demand for oxygen with decreased haemoglobin levels due to infections by parasites”, says Dr. Ishtiaq, talking about the motivation behind this study.
The researchers analysed the parasite DNA in bird blood samples of the 18 species to screen if parasites like Plasmodium, Haemoproteus and Leucocytozoon causing avian malaria were present in them. They also measured the haemoglobin and the percentage of red blood cells in the blood. “Each parasite has a
specific vector group. For example, Plasmodium is transmitted by mosquitoes, Haemoproteus by biting midges (Culicoides), and
that the intensity of infection decreased with elevation in the breeding season.
Measuring the parasite load is vital to evaluate the role of infections on host fitness and physiology, say the researchers. “Our finding brings a new perspective to disease ecology in high
elevation environment where birds are infected with fewer or inactive blood parasite infections”, says Dr. Ishtiaq. “Previous studies have shown that high parasite load is correlated with high mortality rates in human malaria. It is quite possible that a heavyload of blood parasite infections cause excessive damage to the red blood cells of the seasonal migrants, leading to anaemia, and our experimental result supports the same” she adds. So, what does the future hold for these birds, considering climate change is affecting the Himalayan ecosystem? The future seems to bleak according to Dr. Ishtiaq. “Temperature plays an important
role in regulating the transmission of parasites. With increasing global temperature, the range of mosquitoes and blood parasites might expand to higher elevations. Such a situation might exacerbate hypoxic stress experienced by high elevation birds,” she warns.
This article was originally published on Research Matters.
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INDIA ALLIANCE
FELLOW IN SPOTLIGHT
Dr. Benedict Weobong Intermediate Fellow Sangath, Goa Please tell us what you are working on and what impact do you hope it will have.
Why is Mental Health research not a priority, specially in LMICs and how can we promote it more actively in our countries?
My passion to help address some of the myriad of problems has led me to this crazy but exciting idea of leveraging technology such as simple mobile messaging to help adolescents cease to drink in risky ways! This ‘magic pill’ is called POWERTXT, and it’s about harnessing the POWER in a TEXT message to deliver a brief intervention in order to address a behavioural problem that is beginning to assume very alarming proportions. Almost 1 out of every 3 adolescents currently drink at risky levels, and if this is not checked, it could lead to many health, social, and economic problems later in life. Children and adolescents are the future and we have an obligation to help guarantee this future in an increasingly volatile world. POWERTXT is trying to do this, and I am very optimistic that in the next 4 years we may just have ‘discovered’ a ‘cool’ approach (yes, cool because adolescents don’t like to be judged and a bot offers exactly this!) to help adolescents cease to drink in risky ways.
I would place this squarely on the over-dominance of the biomedical model/conceptualization of disease and causation! To many it’s much easier to connect with the notion of a pathogen or germ etc. that can be isolated and shown to cause a disease, and which can be treated with a simple pill or injection. Indeed, I would dare say as a direct consequence, the health system in many low-and middle-income countries (the world over perhaps!) – is based on models of care designed for acute illness, maternal and child ill health and communicable diseases. As a result, it fails to contribute as much as it should to saving lives or alleviating suffering related to mental and neurological conditions. Closely related to this is the very dangerous role of ignorance- to many the interconnectedness between mental ill health and physical health is a mirage and does not exist, plus they don’t know the disease burden from mental health conditions. I remember vividly years gone by being told by a colleague that mental health issues/research is ‘the icing on the cake’! This posturing means potential change agents or effector institutions would find it very challenging to take bold decisions in favour of mental health programmes. In sum, mental disorders are considered invisible in most societies.
What are some of the challenges you have faced so far in carrying out this research? Are some of these challenges specific to India or would these be similar in other countries, including in your home country Ghana? It has largely been quite smooth-sailing- thanks to the fantastic support from my host institution Sangath, Goa. There are always challenges with getting the personnel with the right caliber and this is a ubiquitous challenge in most LMICs and particularly pronounced in the field of mental health. Mental health research capacity and leadership is lacking in LMICs and this presents considerable challenges to mid-career researchers hoping to build and sustain teams necessary for achieving independence. To buttress this, my fellowship provided (or actually encouraged) me to recruit post-doctoral researchers but this has been very challenging. There is also the issue of research management and being able to navigate and fulfil administrative requirements whilst at the same time keeping your eyes locked on the science and project timelines.
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INDIA ALLIANCE FELLOW IN SPOTLIGHT DR. BENEDICT WEOBONG
Benedict with participants at a recent intervention development workshop
There are always ways around these challenges and it’s gratifying to note that the landscape has improved considerably over the last decade and there is now very credible momentum in pushing the mental health agenda. We are beginning to see deep-seated and collective interest from funding agencies, governments, and world bodies such as the UN. This is largely due to the efforts of the movement for global mental health (http://www.globalmentalhealth.org) whose philosophy is the prioritisaton of mental health and equity in mental health for all people worldwide. Knowing that mental disorders are invisible in most societies, the strategy to put mental health on the global agenda has been to make the cause visible to everyone by providing clearly synthesized data on the state of the world’s mental health, the economic consequences (annual global cost attributable to depression alone is estimated at US$1·15 trillion), and more importantly evidence of effective and cost-effective treatments. In parallel with these strategies is the urgent need to develop much-needed research leadership and capacity within LMICs and one innovative strategy is to harness the strengths of established centres/institutions of excellence within the global south through South-South collaborations. This is something close to my heart and I have the unique opportunity to initiate/build this bridge between my host institution Sangath and the School of Public Health University of Ghana.
How has Wellcome Trust/DBT India Alliance funding helped you and your research?
Is there a research area other than yours that interests you deeply?
Finally, if you were not a researcher, you would be?
I guess that would mean I’m probably not in the right place?! No, not really as I really do enjoy being an epidemiologist, and even more exciting to be doing this in the field of mental health research. But I guess there are always other interests and the areas of artificial intelligence and economic evaluation in mental health that fascinates me.
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Opportunity to rack up my track record and be able to be competitive and independent- it’s an open secret that the quality of our research (and thus career growth) is mainly measured by the number of publications we produce, number of citations we get, and the amount of grant money we obtain. Fellowships are by far the best catalyst to achieve these and the India Alliance is offering this. Also guaranteed funding (if you work hard!) and offers the opportunity to conduct focused research without any dependencies! What keeps you going everyday? That there are still unanswered questions! Oh….and I take much of this inspiration from Bradford Hill because “All scientific work is
incomplete and liable to be upset or modified by advancing knowledge, yet this does not give us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time! Indeed, as Robert Browning asked; who knows but that the world may end tonight? True, but on available evidence most of us make ready to commute on the 08:30 next day whether it be observational or experimental”
Patience…. there are often prolonged time scales to reward! and critical thinking are key attributes of a researcher. I think I would do pretty well practicing law or professional acting!
Find out more about Benedict’s scientific journey and current research here.
Is malaria sucking up oxygen in the Himalayan birds?
By Paramananda Barman
OPINION
Rural India faces epidemic of non-communicable diseases Dr. Yogeshwar Kalkonde, Intermediate Fellow
Society for Education, Action and Research in Community Health (SEARCH), Gadchiroli A 46-year-old male labourer with high blood pressure and diabetes, a 55-year-old male farmer who has recently suffered a heart attack, a 52-year-old woman with anxiety and depression, a 56-year-old woman with chronic back pain… A day at my clinic is full of cases that one would be surprised to find in a rural and tribal region of Gadchiroli, one of India’s most backward districts. My friends—doctors and non-doctors alike—are puzzled when I talk about the increasing incidence of chronic non-communicable diseases (or NCDs, for lack of a better word) in rural and tribal regions of India. “But these are the diseases of people who live in cities!” they argue. This dangerous myth needs to be countered. India’s disease pattern is shifting. Unbeknown to most of us, the disease pattern in India in general and particularly in rural India has undergone a significant shift over the last 15 years. An early inkling of this change was evident in a 2001-2003 Government of India report on the causes of death in the country. The report revealed that the deaths in rural India due to communicable diseases (41 percent) were almost matched by those due to NCDs (40 percent). A follow-up study on the causes of death in rural India for the years 2010-13 showed that NCDs accounted for 47 percent of all deaths while communicable, maternal, peri-natal and nutritional conditions together accounted for 30 percent, indicating that NCDs have unquestionably become a healthcare priority. The pattern of NCDs in rural India looks largely similar to that in urban India. High blood pressure, the biggest risk factor for death worldwide, now affects one in five adults in rural India, while diabetes affects about one in 20 adults. We are already in the midst of an NCD epidemic in rural India!
The growing burden of disease Certain chronic diseases such as coronary artery disease, strokes, lung diseases and cancers lead to deaths as well as disability; however, there are several NCDs—such as chronic low back pain, mental health and neurological disorders, anaemia, cataracts and hearing loss—that do not cause death but lead to significant disability. A key metric to measure the burden of a disease on a community is disability adjusted life years (DALYs) lost. It is the sum of years of life lost due to premature deaths and years lived with disability. A recent report released by the India State-Level Disease Burden Initiative shows that three of the top five leading causes of DALYs lost in India were NCDs: coronary artery disease, chronic lung diseases and stroke. The burden of disease is immense. Due to their chronic nature, the significant disability and premature death, NCDs lead to chronic expenditure on health and, thereby, worsen poverty. Loss of productivity and purchasing capacity could lead to slowing of economic growth and development. It is estimated that India is likely to lose USD 4.58 trillion before 2030 due to NCDs. It’s time to take rural NCDs seriously. Given the havoc they threaten to wreak on rural lives, it is time that NCDs are addressed on priority. All the stakeholders, including civil society, businesses, academia and policymakers, need to take a serious note of this new health challenge in rural India where a majority of India’s population lives.
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RURAL INDIA FACES EPIDEMIC OF NON-COMMUNICABLE DISEASES Dr. Yogeshwar Kalkonde
times, catastrophic health expenditures, which push the families into poverty. There is no financial safety net to help people absorb the negative economic consequences of NCDs.
But why are NCDs becoming a problem in rural area? The prime reason is epidemiological transition, which is a shift towards chronic non-communicable diseases along with socio-economic development. Increasing life expectancy and urbanisation of lifestyle in rural India have led to this transition.
5) Lack of systematic mechanisms to collect data on NCDs from rural India could hamper efforts at measuring the problem, guiding interventions and monitoring them effectively.
Since Independence, the life expectancy at birth has increased substantially in India; from 32 years in 1947, it had more than doubled to around 68 years in 2017. The life expectancy in rural India is not very different from that in urban India. This means that more people in rural India are surviving to an age where diseases related to ageing—such as high blood pressure, diabetes and cancers—catch up.
6) NCDs are typically treated by physicians with advanced level of training; since such physicians are not accessible to villagers, the best way to treat NCDs at the village level needs to be understood. NCDs, thus, create a big challenge for healthcare systems—public as well as private—in rural India. The government-run healthcare system in rural India largely focuses on maternal and child health and infection. For instance, of the total health budget of INR 47,343 crore in 2017-18, only INR 955 crore was allotted to the NCD programme. This system now faces the dual burden of tackling not just infections but NCDs as well.
The challenges of tackling rural NCDs There are multiple challenges to managing NCDs in rural India: 1) NCDs in rural India are affecting a relatively younger population—about a decade younger—compared to that in the developed countries. This is likely to be due to malnutrition early in life, which paradoxically increases the risk of NCDs and an unhealthy lifestyle in early adulthood. This means younger population in rural India needs to be screened for chronic diseases.
This would require healthcare policymakers to focus on developing new human resources, technology, healthcare delivery mechanisms and financial resources to tackle NCDs in rural areas. Needless to say, prevention needs to be a priority.
This article was originally published in India Development Review Dr. Yogesh Kalkonde is an India Alliance Intermediate Fellow, a neurologist and public health researcher at Society for Education, Action and Research in Community Health (SEARCH), a non-government organization working in rural and tribal parts of Gadchiroli district in India. Find out more about Yogesh’s current research here.
2) There is very low awareness about these diseases in rural India, leading to further challenges to inculcating lifestyle changes and prevention methods.
3) Facilities for diagnosing and treating these disorders are often not available in rural areas, resulting in late diagnosis and treatment. 4) NCDs lead to chronic expenditures on healthcare and, many
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INDIA ALLIANCE
WORKSHOPS EMBO Research Leadership Course 19-22 March 2018, New Delhi & 26-29 March 2018, Hyderabad The India Alliance, with support from European Molecular Biology Organization (EMBO) organized EMBO Research Leadership course for researchers in India to train them in leadership and management skills that are critical for a successful career in science. Two courses were held from 19-22 March 2018 in New Delhi and 26-29 March 2018 in Hyderabad and were attended by 32 early and mid-career academic researchers from 27 institutions from across India. These were attended by researchers who are not India Alliance fellows as well with a view to strengthening the ecosystem.
“The leadership course was one of its kind. To run a scientific lab or an organisation, one needs to go through similar outstanding Leadership courses. Especially the course sculptors were highly engaging and learned. They were experts in the area of scientific leadership and made us aware about the operational skeleton of day to day interactions with our business group in areas related to scientific leadership etc. I rate this course 10 on a 10 point scale.” Course participant
This was the first time EMBO Leadership Course was organized in India. CJ Fitzsimmons, who delivered the workshop along with his colleague Mr William Uber, has designed this course (Leadership Sculptor®) which he has been conducting in various parts of the world for the last 15 years. He shares his experience below of holding his first-ever Research Leadership course in India.
Eat, Pray, Lead – Our First Experiences With Scientific Leadership in India CJ Fitzsimons
“The one who plants trees, knowing that he will never sit in their shade, has at least started to understand the meaning of life.” — Rabindranath Tagore
One way we sometimes define the task of the leader is this: It is his or her job to prepare the next generation for the challenges they will meet when their time to lead arrives. Naturally, passing along the knowledge we elders have gained over time also has its more immediate rewards. These include seeing the faces of younger colleagues light up with understanding when our message connects with them. And the feeling of satisfaction that arises when we note our charges’ increasing self-confidence and willingness to accept greater responsibility in their teams and institutes. Nonetheless, it is also true that many of the seeds today’s leaders plant will only come to fruition at some remote point in the future. This is the truth implied in the above quotation. When asked, “Why lead?” a veteran of the job might thus answer, “Because I have started to understand the meaning of life!” This multi-layered answer would seem to be typical of India, where the edifice of modern science is being built on an ancient foundation of deep insights into human existence. We recently had the privilege of facilitating two workshops for research group leaders in Delhi and Hyderabad. These followed the familiar format of the EMBO research leadership workshops that we have been conducting for many years in Europe and, more recently, in the United States. This initiative, undertaken as a joint venture with The Wellcome Trust / DBT India Alliance, was part of EMBO’s continuing efforts to promote high-quality training and research among scientists around the world.
continent. Hofstede’s model provides a framework to understand India’s culture. At each step in the process, we made the required minor adjustments, together with the participants, so that the material fit to their environment, which is both more hierarchical and more male-dominated. Based on the response of the participants, it seems clear that the tentative answer to the question of the workshop’s suitability for India is “yes.” Granted, it is in the nature of leadership training that its true utility only becomes apparent after the workshop is over. Before issuing a final judgment, the workshop participants must, therefore, return to their work environments, begin implementing the new concepts and strategies they encountered during our four days together and collect data on the observable effects. Only then will truly reliable information exist. This being said, our experiences with some of India’s best and brightest make us optimistic about the positive ripple effects that may be expected. The eagerness with which the participants threw themselves into the work at hand, the insights revealed via their countless probing questions, their willingness to share openly of their own experiences — both happy and unhappy — make clear that they were not just there as spectators, but as cocreators of a deeply meaningful learning experience and promoters of useful change “back in the lab”. Two moments stand out in particular. During the EMBO module on team dynamics—which includes building a series of dioramas on the floor using colourful plastic figurines – the group became so engrossed in the emerging team sculptures that they slid from their seats and crept, one by one, up to the display. Eventually, virtually the whole group was gathered around the dioramas, sitting cross-legged on the floor, listening to a captivating story. This was a priceless moment and a novum in our experience as facilitators.
One ancillary goal of these two workshops was to learn how to transfer the good leadership practices discussed in the existing EMBO workshops to the research settings found on the sub-
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INDIA ALLIANCE WORKSHOPS
Eat, Pray, Lead – Our First Experiences With Scientific Leadership in India courses. Before closing, we’d like to offer a special vote of thanks to Luis Valente (EMBO) and Shahid Jameel (India Alliance) for making this exciting new venture possible, and our on-site coordinators, Sarah Iqbal and Saritha Vincent, for all their organisational magic to ensure a smooth and most enjoyable visit. Their advance work contributed greatly to the successful execution of the workshops and ensured that we “innocents from abroad” arrived safely and on-time at the appropriate location to carry out our duties — Delhi and Hyderabad traffic conditions notwithstanding. Finally, another quote from India’s great Nobel laureate, Rabindranath Tagore:
CJ and Billy with course participants in Delhi. Photo credit: Dr. Sandhya Koushika
“Reach high, for the stars lie hidden in you. Dream deep, for every dream precedes the goal.”
And, at the end of the workshop, the taking of group selfies (apparently, an inviolable Indian tradition) lasted a good ten minutes, since nearly everyone wanted their own personalized souvenir of the occasion. We now have evidence you can just about squeeze eighteen people into a selfie!
This expresses beautifully our wishes and hopes for all our new friends in India. You have much to offer the world of science and the world beyond science. Reach high, dream deep, and make it so.
Another first for us was the cake of gratitude that suddenly appeared at the end of the course in Hyderabad – evidence of Southern hospitality.
With fondest regards from Baden-Baden,
Google #EMBOIALSLabLead for more tweets and selfies from the
CJ and Billy
Read this article on Leadership Sculptor®
Research Methodology Workshop 12-13 and 14-15 March, 2018, THSTI, Faridabad
The India Alliance established the Clinical and Public Health (CPH) Fellowships program in 2014. In order to make up for a lacuna in understanding of research methodology in clinical and public health researchers, the CPH Committee suggested that a training workshop on Research Methodology would be useful in order for the India Alliance Fellows to perform high quality research. However, it was decided later that the training would be open to basic researchers as well. Consequently, India Alliance organized two 2-day workshops on Research at Translational Health Science and Technology Institute (THSTI), Faridabad.
these workshops. Following feedback was received from some of the attendees of these workshops:
“Had to be the best epidemiology/statistics class ever! Thank you Professor Muliyil for making this course so interesting and interactive.”
The workshops were open to all active India Alliance Fellows. The aim of the workshops was to provide structured training that would help in improving the quality of data collection. The workshops were coordinated by Clinical Development Services Agency (CDSA), which is an extramural unit of THSTI. Prof. J P Muliyil, former Principal of Christian Medical College Vellore, facilitated
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“I have been introduced to these concepts previously but the way sessions are conducted is an indeed a great learning on how difficult concepts can be put across via enjoyable environment.” “The best thing is the course started from very basic ideas and everything is explained with examples and previous studies of real life clinical situation.”
INDIA ALLIANCE
PUBLIC ENGAGEMENT
REPORT
The Undivided Mind: Art + Science Program September 2017- March 2018, Khoj, New Delhi
The Art + Science program aims to promote a dialogue between artists and scientific concepts, phenomena and technology through practice. Instituted by Khoj International Artists’ Association and supported by Wellcome Trust/DBT India Alliance, the Art + Science programme is designed to advance projects that explore artistic applications of emerging thoughts and technologies with the help of partners from the scientific industry and academia. This year the Art + Science Grant funded a small number of projects that engaged emerging themes around science and technology. The grant consisted of a six month research and development period culminated into a four-week residency and Open Studio at Khoj Studios on 29 March 2018. During the research period, selected artists interacted and collaborated with scientists and technologists to develop their project.
Bioartist Darya Warner
The selected residents for programs were: Darya Warner and Puneet Kishore; Sonia Mehra Chawla; Bodhisattva Chattopadhyay, Goutam Ghosh, and Susanne Winterling; and Tulika Aasma, Kaushal Sapre and Abhinav Gupta.
Ghosh, and Susanne Winterling for their project, took off from the two interlinked futurist descriptions of anthropogenic impact on the planet: the desert planet and the drowned world, focusing on investigating the former through a geo-cultural, the biological, and the science fictional lens. Sonia Mehra Chawla’s project Salt Lab reflected on the urgency to develop salt-tolerant and drought resistant crops in India. The project continues to explore both indigenous saline tolerant rice varieties in India, as well as recent developments in transgenic rice. Darya Warner, a bioartist, collaborated with engineer and science researcher, Puneet Kishor, to develop MycoPrinter, an open source 3D bioprinter that prints mycelium substrate ready for inoculation with various types of fungi. The printer brings together engineering, biological sciences and art under the umbrella of open citizen science. The team of young artists and engineers, Kaushal Sapre, Tulika Aasma and Abhinav Gupta, worked with air monitoring data to explore the ideas around sentience, affect and memory by looking at atmospheric envelopes as the primary material for investigation.
The artists presented their work at Open Studio in Khoj on 29 March 2018. The team of Bodhisattva Chattopadhyay, Goutam
For more information on this year’s program, visit http://khojworkshop.org/programme/art-science-iii/
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INDIA ALLIANCE PUBLIC ENGAGEMENT
Women in Science series The Life of Science
India Alliance is supporting the “Women in Science series” an initiative of The Life of Science (TLos) that aims to highlight the work and challenges faced by women scientists in India and to showcase these scientists as role models for young girls. TLoS is a science media platform currently focussed on women scientists in India.
etc. on their website and other popular media channels over the next few months. Below are some of the latest offering from this series. Click on the photo or the text link to read the fascinating science and journeys of some of India Alliance Fellows.
Through this series, TLoS will feature around 30 India Alliance women Fellows through writing pieces, photo features, podcasts,
Nano-pollution is real, warns Madhu A biologist in Chandigarh who studies the darker shades of nanotechnology shares her thoughts on her scientific life and raising a child in one.
A taste of fruit fly research with Pinky
Sreelaja goes fishing for embryos
A neurobiologist talks about her interesting research with fruit flies, dealing with retraction and the realities of Indian science.
A photoessay featuring an embryologist exploring how much our mothers influence the very initial moments of our life
Comic: Sucharita’s Guide to Preventing Diabetes In a research unit in Bengaluru, Sucharita Sambashivaiah and her team of researchers are looking into an unconventional aspect of Type 2 Diabetes, and studying how the disease can be better managed in Indians. This is her story in illustrations.
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INDIA ALLIANCE
NEW INTIATIVES The India Alliance Gateway on Wellcome Open Research India Alliance is pleased to announce the launch of the India Alliance gateway on Wellcome Open Research. As part of its commitment to open research policy, the India Alliance has teamed up with Wellcome Open Research to enable immediate publication of manuscripts, followed by open invited peer review, of its funded research.
referees’ reports. Articles that pass peer review are indexed in PubMed and other bibliographic databases.
Wellcome Open Research is an online platform that publishes research output funded or co-funded by Wellcome. On this platform, all articles are published rapidly as soon as they are accepted, after passing an in-house quality check. Peer review by invited experts, suggested by the authors, takes place openly after publication. An article remains published regardless of the
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Authors are encouraged to respond openly to the referee reports, which are published with the article, and can publish revised versions of their article, if they wish. Read more about Wellcome Open Research’s post-publication peer-review model. Find India Alliance Fellows’ open research at https://wellcomeopenresearch.org/gateways/IA and a list of gateway advisors that are championing the brave new practice of open access publishing.
INDIA ALLIANCE NEW INTIATIVES
India Research Management Initiative (IRMI)
Participants at the IRMI sharing session at IISER Pune
make use of competitively won external resources appear to have been slower to develop in India.
Good research management is crucial for research and enables researchers to access new funding opportunities, navigate changing schemes and policies at agencies, receive support for team science programs and effective grant management and helps ensure that research findings are used effectively. A Scoping Study on research management in India commissioned by the Wellcome Trust in 2016 and a panel discussion on professional research development offices at Indian institutions, hosted at the India Alliance Annual Fellows Meeting in 2017, highlighted the need for developing this part of the Indian research ecosystem. IRMI, the India Research Management Initiative, was subsequently launched by the India Alliance in February 2018, for building capacity in research management at organizations in India.
An IRMI sharing session was recently organized at IISER Pune on 19 April 2018, which included attendees from the scientific leadership at participating institutions along with research managers. The format of the workshop allowed for in-depth sharing of ideas on the benefits of research management along with a detailing of the barriers to implementation, from the varied perspectives of institutions and individual research managers. More such workshops are planned in other parts of India during the IRMI pilot phase in 2018. This would provide a comprehensive view of research management in India, which in turn is expected to guide future policy and specific funding opportunities via the India Alliance.
IRMI will be developed along a framework that encompasses four themes: • Generating leadership support for research management in India • Making research management offices sustainable • Identifying common standards and good practice for research management • Individual capacity development: ensuring recognition of research management as a profession and developing a pool of qualified staff IRMI is initially being implemented as a pilot phase aimed at establishing a detailed account of research management at Indian research institutions and identifying gaps in the system. There are now 17 research institutions and Universities registered with IRMI and this has allowed the India Alliance to develop a baseline of research management in India, guided by the IRMI framework. With an increasing number of institutions registering for IRMI, this knowledge-base is expected to become more comprehensive. Early conversations suggest that universities and research institutes have the staff, processes and management in place to receive core funding from specific arms of government. However, systems to help researchers compete for, negotiate, manage and
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IRMI sharing session at IISER Pune
Institutions wishing to participate in IRMI should complete a registration form available on the Wellcome Trust/DBT India Alliance website via the link https://www.indiaalliance.org/news/203 and completed forms should be sent to IRMI@indiaalliance.org. IRMI in the media - Research management critical for Indian labs to become competitive - Dr. Savita Ayyar, Lead, IRMI
INDIA ALLIANCE NEW INTIATIVES
The Africa-India Mobility Fund (AIMF) is a two-year programme designed to provide researchers from Africa and India with opportunities for short visits in either direction to explore opportunities for building and strengthening scientific collaboration.
improve research capacity and build leadership in biomedical and clinical research for Africa and India.
The AIMF initiative by the Wellcome Trust/DBT India Alliance (India Alliance) and the African Academy of Sciences intends to encourage South-South collaborations and learning between the two ecosystems. This is in recognition of the fact that Africa and India face similar challenges, both in the diseases that affect their populations and socio-political issues as well as the leadership required to address these. The exchanges are expected to enhance their skills and contribute to the growth of knowledge and leadership towards common health challenges. In Africa, the travel grants will be administered by the Alliance for Accelerating Excellence in Science in Africa (AESA) and in India by the India Alliance.
Objectives • To strengthen research & innovation capacity and knowledge exchange • To strengthen scientific collaboration between Indian and African teams Scope Applications broadly focused on infectious and noncommunicable diseases of relevance to local, national, or global health will be accepted every month. The scope of the collaborative opportunity may include but is not limited to HIV/AIDS, TB, dengue, malaria, vector-borne diseases, parasitic infections, emerging infections, cancer, diabetes, hypertension, health systems research, antimicrobial resistance, drug development, microbiome and general biomedical sciences.
The AIMF comes on the heels of the Third India-Africa Forum Summit held in October 2015 and where Heads of State adopted the Delhi Declaration renewing their commitment to work with each other, and outlining the priority areas and ways in which Africa and India can work together to improve the lives of their people. It is also one of many efforts to exploit the synergistic relationship between Africa and India outlined in the India Africa Health Sciences Summit held in 2016. Over the last two years, the India Alliance and AESA have also hosted African and Indian biomedical researchers, respectively, at their Annual Grantees Meetings.
While applications that involve existing collaborations will be considered, applications that target new collaborations and encourage diversity especially female and young applicants are particularly encouraged.
These travel grants will be supported by the India Alliance (for Indian researchers) and the Wellcome (for African researchers, administered through AAS and AESA).
References:
Application Process, Review and Deadlines All application forms should be submitted through the AAS Grants Management System (Ishango). Register as a user to apply. See sample application form here Click here to find out more about these travel grants.
Why it’s time African researchers stopped working in silos. The
Conversation. May 2016
Purpose, Objectives and Scope of the Initiative Purpose To establish links and cultivate a culture of collaboration between African and Indian researchers that will serve as a vehicle to
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Health research: Africa–India health-science partnerships. Nature. September 2016 Outwards to Africa. The Hindu, September 2016 Bringing together African and Indian Biomedical Researchers. India Alliance Newsletter, September 2016 India meets Africa again: Recognising common research goals and mapping the road ahead. India Alliance Newsletter, September 2017
OTHER ANNOUNCEMENTS
Download India Alliance Annual Report 2017-18
Please send your feedback, suggestions and contributions to public.engagement@indiaalliance.org Follow us on www.indiaalliance.org 26.