India Alliance Newsletter
News & Views Issue 1, January 2015
EDITORIAL “Science knows no country, because knowledge belongs to humanity, and is the torch which illuminates the world. Science is the highest personification of the nation because that nation will remain the first which carries the furthest the works of thought and intelligence. “ Louis Pasteur
The Wellcome Trust/DBT India Alliance strives to support and encourage biomedical research in India by introducing innovative and unique funding models. Since its inception in 2009, the India Alliance (IA) has attempted to promote the best scientific talent in the country and has constantly endeavoured to reach out to a larger scientific as well as non-scientific community through its various programmes and events. Our newsletter is one such effort in that direction. The purpose of this bimonthly newsletter is to inform everyone about our Fellowship schemes, outreach and public engagement activities and act as an important mouthpiece of the Alliance. We also hope to encourage discussion on issues related to biomedical research and scientific explorations in general through various articles and interviews. Lastly, we have a diligent and enthusiastic IA team working behind the scenes who will be featured in the newsletter every now and then. Our maiden issue features announcements for our Research Fellowships for Clinicians, upcoming Science Communication workshops, a brief on our on-going DNA@70 public lecture series and Public Engagement Competition for our Fellows. The Research Highlights section mentions the recent research breakthroughs of our Fellows, Neha Vyas, Urvakhsh Mehta, Amit Singh, Arun Shukla and, Mahendra Sonawane. We would like to thank our Intermediate Fellow, Pallab Maulik, for writing an informative piece on mobile-based healthcare delivery in rural India. We also extend our heartfelt gratitude to Prof Nadrian Seeman who shared with us in an interview, his scientific beginnings, views on the future of DNA nanotechnology and his advice to young scientists. The Feature article titled, From the Human Genome to Proteome – unraveling the puzzle, piece by piece, talks about the rise of the „omics‟ era and features the work of our Fellows, Harsha Gowda and Mukund Thattai. The newsletter ends with a light-hearted and enjoyable account by our Programme Manager, Megha Sharma, on her India Alliance journey, general interests and what inspires her. This issue would not have been possible without the contributions of all the aforementioned people and useful inputs from Madhankumar Anandhakrishnan, Ajay Pillai and, Ranjana Sarma of the India Alliance. Please do not hesitate to write to us with your suggestions and comments. We hope you enjoy the first of what we hope to be many issues to come.
Sarah Iqbal Public Engagement Officer Wellcome Trust/DBT India Alliance
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CONTENTS 3
AN OVERVIEW OF INDIA ALLIANCE FELLOWSHIPS
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CALL FOR IA FELLOWSHIP APPLICATIONS Announcement for Clinical & Public Health and Research Training Fellowships
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UPCOMING EVENTS & PUBLIC ENGAGEMENT SciComm Hyderabad, SciComm101, Public Lecture series, Public Engagement competition for fellows
IA FELLOW‟S RESEARCH HIGHLIGHTS Featuring recent research articles of Neha Vyas, Urvakhsh Mehta, Arun Shukla, Amit Singh, Mahendra Sonawane
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VIEWPOINT Harnessing mobile technology to provide basic health care in rural India by Pallab Maulik, India Alliance Intermediate Fellow
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IN CONVERSATION WITH.. Prof Nadrian Seeman, ‘inventor of the field of DNA nanotechnology’ Margaret and Herman Sokol Professor of Chemistry at New York University, USA
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FEATURE ARTICLE From the Human Genome to Proteome – unraveling the puzzle, piece by piece by Sarah Iqbal, India Alliance Public Engagement Officer
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INDIA ALLIANCE STAFF CORNER Megha Saraswat Sharma, Programme Manager
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AN OVERVIEW
INDIA ALLIANCE FELLOWSHIPS India Alliance Fellowships are available across the full spectrum of biomedical research - from fundamental molecular and cellular studies through to clinical and public health research. Research projects can be based in the laboratory, the clinic or the field and may involve experimental or theoretical approaches. The Table below gives a general overview of all the Fellowships we offer. Criteria
Early Career
Intermediate
Senior
Margdarshi
Eligibility (postPhD/MD/MPH)
-1 to 4 years
4 to 7 years
7 to 15 years
Independent PI for > 10 years
Duration
5 years
5 years
5 years
5 years
Budget cap
₹1.7 crores
₹3.6 crores
₹4.5 crores
₹10 crores
Consumables
Yes
Yes
Yes
Yes
Major equipment
No
Yes
Yes
Yes
Support staff
No
Up to 2, including postdocs
Up to 4, including postdocs
As per need, including Assistant Professors
Work Outside Host Institute
Up to 2 years, $3000/month
Up to 1 year, $3000/month
As per need
As per need
Travel to Meetings
₹7.5 lakhs
₹7.5 lakhs
₹10 lakhs
As per need
Contingency
₹2.5 lakhs
₹7.5 lakhs
₹10 lakhs
As per need
For further information please visit our website
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INDIA ALLIANCE FELLOWSHIP ANNOUNCEMENT
FELLOWSHIPS FOR CLINICAL & PUBLIC HEALTH RESEARCHERS 2 February, 2015 Deadline: 16 March 2015
Preliminary applications are invited for the three Fellowship schemes: Early Career Fellowships, Intermediate Fellowships and Senior Fellowships. These Fellowships are designed to encourage interested clinicians and public health researchers to pursue their research goals in combination with their clinical duties. There is no age or Nationality restrictions and the candidates need not be resident in India while applying but should be willing to establish an independent research career in India.
RESEARCH TRAINING FELLOWSHIP FOR CLINICIANS 2 February, 2015 Deadline: 30 April 2015 India Alliance announces its 'Research Training Fellowship for Cliniciansâ€&#x; meant to facilitate their transition to a clinical researcher. This opportunity is aimed at providing clinicians with an opportunity to perform high quality basic or clinical research in a laboratory or clinical environment of their choice.
Application form will be available on the India Alliance website from 2 February, 2015. Please visit our website for further information on the application process.
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UPCOMING EVENTS
SCIENCE COMMUNICATION WORKSHOPS
SciComm Hyderabad
20-21 March, 2015 Hyderabad
In keeping with our mandate to empower future leaders of Indian science, the
20-21 March, 2015
India Alliance organizes two-day workshops for young scientists in biomedical sciences. These workshops are a unique opportunity for PhD students, Postdoc scholars and Clinician researchers to receive training in written and oral communication skills. These workshops will also provide an opportunity to the young researchers to discuss various issues pertaining to their research career including mentorship, career planning and ethical aspects of scientific research. The workshops aim at skill as well as perspective building for the most aspiring young researchers by bringing young scientists and senior mentors together to provide a platform for discussion and learning.
We are pleased to announce our 11th two-day Science Communication Workshop that will be held in Hyderabad on 20-21 March, 2015. The details of the venue will be shared nearer the time.
SciComm101
23 Jan, 2015 IIT Kanpur
In response to the rising numbers of requests from various academic research institutions to train more students on science communication skills, the India Alliance conducts a one-day variant of the SciComm workshop, SciComm101. These workshops have already been held at various institutions and Universities across India, such as, ILS & NISER Bhubhaneswar, Madurai Kamaraj University and IIT Madras. Participation in these workshop is by invitation only and is at the discretion of the host institution. We have so far trained more than 300 PhD and
medical students in research ethics, manuscript and grants writing, and effective presentations since itâ€&#x;s launch in March 2014.
The next SciComm101 is scheduled to be held at IIT Kanpur on 23 January 2015.
For more details visit "Scicomm Workshop" under "Quick Links" on our website
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INDIA ALLIANCE PUBLIC ENGAGEMENT
DNA @ 70 PUBLIC LECTURE SERIES In 1944, Oswald Avery together with Colin MacLeod and Maclyn McCarty made the landmark discovery that deoxyribonucleic acid (DNA) and not proteins carry genetic information and is therefore the basis of inheritance. In the 70 years since Averyâ€&#x;s discovery, DNA has come a long way. Besides being the basis for major discoveries in biomedicine, the genomes of humans and various other species have been fully sequenced providing fascinating insights into evolution and behavior. DNA is now being developed as a medium for computing, nanorobotics and nanoelectronics. The technologies developed to sequence DNA have also provided a powerful platform to discover new life forms, especially new pathogens that mysteriously cause disease in human and other species.
The Wellcome Trust/DBT India Alliance is celebrating the discovery of DNA
through a series of public lectures across India. The first two lectures in this series were given by Prof W Ian Lipkin and Prof Nadrian Seeman. Announcement for the next speaker in this lecture series will be made shortly.
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INDIA ALLIANCE PUBLIC ENGAGEMENT
PUBLIC ENGAGEMENT COMPETITION for Fellows
Besides its Fellowship Programme, the Wellcome Trust/DBT India Alliance aims to enhance the public understanding of science in India. It has become increasingly important for scientists to engage with the public to increase the awareness of science, technology and medicine (STM) research, and themselves get fresh perspectives on their research towards a larger picture. With this in mind, India Alliance announced a rolling „Public Engagement competition‟ for our Fellows last year. This is a valuable opportunity for IA Fellows to showcase their work and share it with the public. The engagement can be through research, social activities, teaching, science movies/documentaries and other modes of knowledge sharing with the central goal of educating and improving public awareness of STM.
To apply, please download the application form here and send the completed form to public.engagement@wellcomedbt.org. Applications already submitted are under review.
Example of a Wellcome Trust supported Public Engagement initiative “The Dharavi Biennale” is an art and health festival to bring local artists, the community in Dharavi and health researchers together to create artistic pieces and explore issues in urban health.” Photo and text credits: Dharavi Biennale, Wellcome Trust, UK
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INDIA ALLIANCE
RESEARCH HIGHLIGHTS Vesicular Sonic Hedgehog: Companions matter Neha Vyas, Early Career Fellow inStem, Bangalore
Hedgehog (Hh) proteins are signaling molecules in the cell that are anchored to the cells that produce them. Signaling via Hh proteins is essential for activating expression of different genes in the neighboring signaling efficient cells. This eventually shapes the developing tissue. Mechanisms of Hh release into the extracellular milieu along with its anchors have been a subject of intense investigations. Our study uncovers a previously unappreciated complexity in Hh signaling that show that Sonic Hedgehog (Shh; vertebrate Hh) is secreted out of the producing cells on two types of vesicles. These vesicles are transport carriers/bags which carry proteins and cellular molecules from one cell to another. We havecharacterized these vesicles using biochemical approaches and functional assays. We found that the vesicles that ferry Shh also contain other critical helper proteins and regulatory molecules and the ability of Shh to activate target genes also depends on these helper proteins. We demonstrate that blocking these helper proteins inhibits activation of Shh-dependent functions. Our findings thus support a new model where packaging of Shh on vesicles along with other signaling proteins critically affects its function. Such complex signaling mechanism might have significant implications not only in tissue development but also in diseases such as cancers. Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties. Vyas N, Walvekar A, Tate D, Lakshmanan V, Bansal D, Cicero AL, Raposo G, Palakodeti D, Dhawan (Dec, 2014). Scientific Reports
Mirrors in the mind Urvakhsh Mehta, Early Career Fellow NIMHANS, Bangalore
Mirror neuron dysfunction in schizophrenia and its functional implications: A systematic review. Urvakhsh Meherwan Mehta, Jagadisha Thirthalli, Dhandapani Aneelraj, Prabhu Jadhav, Bangalore N. Gangadhar, Matcheri S. Keshavan (Nov., 2014). Schizophrenia Research
Mirror neurons are specialized nerve cells that have unique properties of being active while performing an action, as well as, while observing someone else perform the same action. These neurons are located (figure-A) in the ventral premotor cortex, inferior frontal gyrus, inferior parietal lobule, insula and posterior superior temporal sulcus. While an under-responsive mirror system correlated with the persistent negative symptoms, social cognition and selfmonitoring deficits, an over-responsive mirror system had links with the phasic catatonic symptoms, affective instability and hallucinations (figure-B). This systematic review found preliminary, yet consistent evidence for a dysfunctional mirror neuron system in schizophrenia. A
B
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INDIA ALLIANCE
RESEARCH HIGHLIGHTS “Shock-and-kill” strategy for HIV-1 Amit Singh, Intermediate Fellow IISc, Bangalore One of the unique features of the AIDS virus, HIV-1, is that it can exist inside human cells for years without causing any harm. It then reactivates to cause infection when conditions are suitable. We have exploited a non-invasive biosensor that can measure what is going on within HIV-1 infected cells in real-time. This technology led us to carefully manipulate antioxidant levels of HIV-1 infected cell to either keep virus in a sleeping mode or trigger its reactivation. This may allow researchers to adopt a “shock-and-kill” strategy in which virus could be reactivated by mild oxidants and subsequently flushed by current anti-HIV drugs. Measuring Glutathione Redox Potential of HIV-1 Infected Macrophages. Ashima Bhaskar,Mohamed Husen Munshi, Sohrab Zafar Khan, Sadaf Fatima, Rahul Arya, Shahid Jameel and Amit Singh (Nov., 2014). Journal of Biological Chemistry
AWARD: Amit Singh has been awarded senior Innovative Young Biotechnologist Award(IYBA) by Department of Biotechnology, India.
New understandings of the complex molecular dance on the cell membrane Arun K. Shukla, Intermediate Fellow IIT Kanpur Our body encounters and responds to a wide range of stimuli such as various chemicals and pathogens every day. Cells in our body receive these signals and respond accordingly by initiating diverse cellular events to handle such stimuli. Embedded in the cell membrane, a family of proteins known as G-protein-coupled receptors (GPCRs) is critically involved in this signal recognition and subsequent signaling outcomes. GPCRs represent the largest class of drug targets in the human genome and about half of the currently prescribed medicines (eg. hypertension drugs, heart failure medicines, anti-allergy medication)work by turning these receptors "on" or "off" in our body. In our work, we highlight the diverse mechanism of ligand-receptor interactions for a series of different GPCRs and identify crucial interaction networks that mediate the first step of drug binding to their respective receptors. Our analysis not only provides key insights into the basic understanding of signal recognition by GPCRs but it might also have potential application towards novel drug design. SnapShot: GPCR-Ligand Interactions. Eshan Ghosh, Kumari Nidhi, and Arun K. Shukla (Dec., 2014). Cell.
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INDIA ALLIANCE
RESEARCH HIGHLIGHTS New insights into the mechanisms involved in the maintenance of epidermal integrity in zebrafish Mahendra Sonawane, Senior Fellow TIFR, Mumbai
Epidermis is the outermost multi-layered epithelial tissue that acts as a barrier against various pathogens and helps prevent loss of fluids. The key parameters that determine epidermal tissue growth and architecture are cell number, cell size and cell shape. In our recent publications, we have uncovered two phenomena concerning cell size and cell shape regulation in the epidermis in a zebrafish model. Using mutations in myosin Vb, a gene that encodes for an actin based molecular motor, we have shown that the balance between uptake of plasma membrane components by endocytosis and their recycling is important for the maintenance of cell size and control of cell proliferation in developing zebrafish epidermis (Sonal et al, 2014). In another study, we have shown that the Wnt signalling regulates synthesis of laminins, the extracellular matrix components, to establish an epithelial pattern in the median fin fold, which is an evolutionarily ancient unpaired appendage formed of the epidermis. We further show that this mechanism is conserved in pectoral fins that are evolutionarily recent appendages homologous to tetrapod (four-limbed vertebrates) limbs (Nagendran et al, 2015).
Model showing the regulation of epithelial patterning in zebrafish fin-fold epithelium by the canonical Wnt signalling gradient
Canonical Wnt signalling regulates epithelial patterning by modulating levels of laminins in zebrafish appendages. Nagendran M., Arora P., Gori P., Mulay A., Ray S., Jacob T., Sonawane M. (2014). Development
Irregular cell shape and size in Myosin Vb deficient embryos compared to wild-type
Myosin Vb mediated plasma membrane homeostasis regulates peridermal cell size and maintains tissue homeostasis in the zebrafish epidermis. Sonal, Sidhaye J., Phatak M., Banerjee S., Mulay A., Deshpande O., Bhide S., Jacob T., Gehring I., Nuesslein-Volhard C., Sonawane M. (2014) PLoS Genetics
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VIEWPOINT
Harnessing mobile technology to provide basic health care in rural India Pallab Maulik India Alliance Intermediate Fellow The George Institute for Global Health, India Source: cio.com
Healthcare in India is an expensive affair given that 75% of it is provided by the private sector. It is not surprising to find many people, especially those who are poor and also many within the relatively affluent middle-class section of the society, become financially impoverished even further following major health related expenses. While some of such high medical expenses may be unavoidable given the nature of the illness and the treatment provided, often a lot could have been avoided if adequate steps were taken in early stages of the illness to prevent it from reaching such an advanced stage. This is especially true for some chronic ailments related to cardiac diseases, diabetes, mental illnesses, renal diseases. Often the amount of care needed at early stages of diseases like high blood pressure, diabetes, depression, etc, are relatively easy, and can be provided by non-specialists at primary care level. These conditions also account for some of the highest rates of death and disabilities in the country, hence treating them early makes a lot of sense. The case for mobile based health care
In order to provide care for such conditions at early stages, one needs to operate the primary care system effectively. Providing good quality primary care by empowering non-specialist physicians and non-physician health workers like Accredited Social Health Activists (ASHAs) or similarly trained health workers through basic training and adequate technical support is more important in countries like India with huge populations, as it is close to impossible to expect that there would ever be adequate number of trained specialists, or that there would be such across every geographical area of a country as diverse as India. Besides training primary healthcare workers, there is an urgent need for exploring and developing alternate methods of providing healthcare using easily available and affordable techniques that can increase the reach of care into the more disadvantaged sections of the community.
One such way is to harness mobile technology and make use of more than 900 million currently connected mobile phone users in the country. This is an ever increasing number with more and more people switching to smart phones every day. Interestingly, 300 million of those who have mobile phones, are in rural areas (a number similar to the population of the US), where providing basic health care for preventable diseases is of utmost need, given the even poorer health services
Typical village setting from the area where George Institute, Hyderabad, is testing its mobile based clinical decision support tools
facilities in our rural sector.
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VIEWPOINT Harnessing mobile technology to provide basic health care in rural India
At the heart of mobile based healthcare delivery system lies a good clinical decision support tool. One needs an evidence-based clinical decision support tool (diagnosis and treatment guidelines) that can be based on a mobile platform, and can be easy to navigate and understand. This needs to be supported by adequate re-training of primary care health workers – both doctors and non-physician health workers – to use such clinical decision support tools effectively. At times, specialists are needed to provide support for the more complicated cases and such linkages should be established to complement the system. If such a system is supplemented by appropriate health promotion and treatment adherence information that can be shared with individuals, again using mobile technology, it could build on the success of the mobile-based health platform. Luckily for some of the more common conditions related to high blood pressure, diabetes, depression, alcohol use, there are simple diagnosis and treatment guidelines which are now being adapted for mobile platforms and are supported by primary care staff training. Such tools can also be linked with simple tools that can carry out blood tests and measure blood pressure and weight. These point of care, Bluetooth enabled devices, enhance the capabilities of the clinical decision support tool manifold. One such device to assess cardiovascular disease risk by measuring blood pressure and blood glucose is being tested in a cluster randomized controlled trial in rural Andhra Pradesh by us of the George Institute which uses Bluetooth technology attached to a mobile based clinical decision support tool.
Some challenges for mobile based health care in India
Delivering healthcare through mobile in India has its own challenges, and the key ones are the affordability of smart phones due to cost, and connectivity issues. The basic phones are limited by the amount of text/characters that can be sent as message and have been used to provide simple health promotion messages and
Prototype mHealth tool created by us at the George Institute using the mhGAP algorithm of WHO
gather some basic information. However, the limitations of „basic‟ phones lies in their computing and processing powers that are needed for providing clinical algorithms that form the backbone of clinical decision support tools. The fact that, in India, smart phones are still not widely used can be seen by some as a limiting factor. While it is true that in India smart phone use is relatively new and is not quite affordable currently , the price of smart phones is dropping rapidly and now 3G enabled smart phones are available at less than Rs 3000 compared to Rs 1200 or so for a basic phone. One also needs to be cognizant of the fact that more and more companies are phasing out basic phones and replacing them by smart phones which are pushing the prices down even further. Mobile connectivity across India, especially in rural regions, is also improving and it is not surprising to find rural homes with mobile phones but no land-line connectivity. Hence, it is not too improbable that within a few years, smart phones rather than „basic‟ phones may become more common and as a consequence will make mobile-based health delivery easier.
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VIEWPOINT Harnessing mobile technology to provide basic health care in rural India
Another point is that of connectivity. Smart phones are relatively self-contained and the generation of clinical algorithms is not dependent on connectivity. But, in order to make the whole mobile-based health system more interactive, it is essential to link the non-physician health workers in villages (who are practically the first contact with healthcare for most villagers) with the individual at one end and the primary care physician at the other end. Connectivity is needed to ensure that non-physician health workers can share and receive health information with both the individual and doctor. Connectivity is also an issue if one expands on the model and links it with micro-financing and health insurance - additional components of an integrated advanced mobile-based health care delivery platform.
An additional factor that can be both boon and a bane for mobile healthcare in India is the number of software engineers, entrepreneurs and innovators available in the country. Every passing day is seeing a new avatar of a healthcare application being developed and launched. While this obviously increases the choices for consumers, the main disadvantage of such proliferation of mobile based applications lies in the fact that neither are all such applications evidence based or tested using rigorous methods, nor are they supported by adequate training of health staff to make them effective tools for use by current health staff. The quality is often questionable and the value of such applications is still to be evaluated. Thus, consumers should be careful about any “off the shelf” devices and applications that identify problems and suggest “steps to get better”. A good mobile based health care tool, while on one hand amplifies the existing diagnostic and treatment capabilities of the health workers, on the other hand they also help in increasing awareness about illness amongst the individuals as they get exposed to these mobile based devices on a more regular basis and therefore get to question the health staff about their health status regularly. Developing such good mobile based devices and evidence based clinical decision support systems need adequate time, research and resources. They need to be backed by scientific knowledge and rigorous research, and built on a platform that involves the primary healthcare system. The bottomline
In conclusion, one needs to realize that in a country like India mobile-based delivery of primary health care or even secondary health care is essential, practical, and deliverable. Not all, but many of the health conditions can be effectively treated using existing guidelines. However, to do so effectively both the government and non-government sectors need to think beyond the current healthcare tools and take adequate steps to develop research and infrastructure capabilities to enable such a system. The efforts made by research organizations need to be boosted by government mechanisms and funding agencies, such that scaling up can be done smoothly when the time comes. The George institute for Global Health India is currently working on two such projects in the management of common mental disorders like depression, stress and suicidal risk, and increased blood pressure, in rural Andhra Pradesh. Both these projects are utilizing mobile based electronic clinical decision support tools to identify people in the community who suffer from such conditions, refer them to primary care physicians for evidence based diagnosis and management and follow up. The whole system is complemented by a robust monitoring and feedback mechanism by which treatment provided by doctors can be shared with the village health workers who can then use it to monitor patient progress in their communities. Harnessing mobile technology to provide basic health care in rural India is no longer a dream but a reality.
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IN CONVERSATION WITH..
Prof Nadrian Seeman
Prof Nadrian Seeman, credited for inventing the field of DNA nanotechnology, was the second speaker for our DNA@70 Public Lecture Series. He is currently the Margaret and Herman Sokol Professor of Chemistry at New York University, USA. In this interview he has shared his scientific beginnings, views on DNA nanotechnology and message for young scientists. What motivated you to become a Scientist? If you were not a Scientist you would be... I was motivated by the desire to make a difference in the world, and increasing knowledge or developing new scientific methods seemed a good way to do it. Since a lot of what I do in science has an aesthetic component, perhaps I would be an artist. I can‟t draw or sculpt, but can do computer graphics, and ought to be able to learn 3D printing methodologies.
What led you to the field of DNA nanotechnology? In early 1980s, I was in a pub pondering 6-arm DNA junctions when I thought about M. C. Escher‟s woodcut Depth that gave me an idea of how to go about self-assembling crystals from branched junctions the same way Escher made one from 3D fish. I was doing what interested me but after about 4 years, I was told that it was nanotechnology.
M.C Escher‟s Depth
Kollam design at Meenakshi temple
Prof Seeman visualises DNA nanostructures through art
Where do you see the field of DNA nanotechnology heading in the next decade or so? I am hoping that there will be more activity in 3D work. Certainly that‟s where my lab is headed.
What is the best advice you have ever received? When I was making knots about 20 years ago, I mentioned to a colleague that I wasn‟t sure why, except that I could. He told me to keep doing what I thought was useful, and ultimately we used those knots to show that there is an RNA topoisomerase.
Your message for the young Scientists. My message for all young scientists is to follow your nose, and don‟t be engulfed in the latest trends. To learn more about Prof Seeman‟s work visit his research lab page
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FEATURE ARTICLE
From the Human Genome to Proteome – unraveling the puzzle, piece by piece Oswald Avery Colin MacLeod and Maclyn McCarty
Francis Crick & James D Watson
Sarah Iqbal, India Alliance
"If we are right, and of course that is not yet proven, then it means that nucleic acids are not merely structurally important but functionally active substances in determining the biochemical activities and specific characteristics of cells and that by means of a known chemical substance it is possible to induce predictable and hereditary changes in cells. This is something that has long been the dreams of geneticists." --Oswald T. Avery, 1943
Seventy years since Oswald Avery together with Colin MacLeod and Maclyn McCarty published work highlighting DNA as the hereditary molecule, to a decade or so after the completion of the Human Genome Project (HGP), the wealth of knowledge we possess in the field of genomics today is enormous. The completion of the HGP was the First X-ray image of the DNA
dawn of innovative and groundbreaking research strategies that kickstarted the era of „omics‟ to tackle human health problems. HGP was a trailblazer in the field of biological research on various levels. Not only did it give rise to enormous amounts of biologically useful data, but in the process it also led to the development of various cutting-edge technologies and genomic maps of several other organisms and drastically reduced costs and time for DNA sequencing. HGP is hailed as
Maurice Wilkin‟s letter to Francis Crick
a perfect model for „open access research‟ and successful international collaboration. It completely changed the scientific mindset and expanded possibilities. Soon after the completion of HGP, various genomics research labs flourished around the world and exploited the amassed genomic information to understand different disease pathologies. One such effort is the Structural Genomics Consortium, an international consortium of scientists that use a combination of genomic mapping data and 3-D protein structures relevant to human diseases to develop innovative drug discovery strategies and have an open access research policy like the HGP. HGP generated enthusiasm not just among scientists but also in the public sphere and redefined the future of scientific policies that were to take shape.
When the idea of sequencing the whole human genome was first discussed in 1985 at a meeting convened by the then University of California chancellor, Robert Sinsheimer, it was thought to be crazy. Today, thanks to the successful conclusion of HGP, such „crazy ideas‟
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FEATURE ARTICLE From the Human Genome to Proteome – unraveling the puzzle, piece by piece
are finding more „doers‟ and „funders‟. One such brainwave was the mapping of the Human Proteome. Two concurrent but independent studies have recently come up with a map of the Human Proteome, extraordinary findings of which were published in Nature at the same time. The first study, led by Akhilesh Pandey of Johns Hopkins University School of Medicine in Baltimore,
Harsha Gowda
utilised cutting-edge mass spectrometry to map proteins that encoded for almost 84% of the genes in the human genome, using different adult and fetal human tissues, and purified primary hematopoietic cells (blood cell precursors). They also identified nearly 200 novel proteins by employing a unique research strategy called „proteogenomics‟ where they found evidence of proteins translated from, regions in the DNA that were not thought to be translated, non-coding RNAs and pseudogenes. Harsha Gowda, an India Alliance Early career Fellow based at Institute of Bioinformatics, Bangalore, who co-led this study with Akhilesh Pandey, believes that the „Human Proteome Map‟ would be essential in identifying biomarkers and therapeutic drug targets in disease pathologies specially affecting those tissues. The second study to map and assemble the human proteome took shape in Germany, led by Bernhard Küster of Technische Universität München. Part of their approach, however, was different from their peers as 60 % of the human proteome data they analysed was either collected from their colleagues or from the public databases. The other 40% of the data they generated came from mass spectrometric analyses of various human tissues, body fluids and cell lines. They obtained proteomic information for 92% of known protein-coding genes and also found various new proteins from regions of non-coding RNA. The Human Protein Atlas is another such effort to put together the map of human proteins in an exhaustive manner. The Atlas is also publicly available and includes “high-resolution cell images showing the distribution of proteins in 44 different normal human tissues, 20 different cancer types, as well as 46 different human cell lines”.
Information generated from these proteomics studies, in combination with the HGP data and the on-going genomic mapping efforts, have now enabled researchers to understand and solve the molecular complexities in greater detail. They have also given rise to the concept of „personalised medicine‟ where these findings are being exploited to develop treatments tailored based on an individual‟s genomic, and now proteomic, fingerprint. These genomic and proteomics data will also give useful insights into the most intriguing questions surrounding human evolution and will enable us to identify differences on genetic and cellular levels between species. The Mouse Encode Consortium strives to ascertain and map these evolutionary differences and published their recent findings in Nature. Mouse models are commonly used in biomedical research to study disease pathologies even though only half of our genome overlaps with the mouse genomic DNA and there is very little information available that describes the genomic differences between the two. Scientists in this consortium are trying to identify these key genetic differences and their implications on pathogenic mechanisms which could help researchers use these animal models more conclusively.
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FEATURE ARTICLE From the Human Genome to Proteome – unraveling the puzzle, piece by piece
One of our Intermediate Fellows, Mukund Thattai, who works in the area of evolutionary cell biology at National Centre for Biological Sciences, Bangalore, endeavours to understand how these evolutionary forces play at the cellular level. Mukund combines Mukund Thattai
analysis of genetic maps of various organisms and cell biological
experiments to explore how the expanding genomic repertoire of eukaryotes drove the evolution of cell organelles and organisation, over two billion years. He used phylogenetic analysis to show how ancient prokaryotic mitochondrial division apparatus is found in some of the ancient surviving eukaryotic organisms such as, red algae, diatoms and ameobozoans and has remain unchanged over billions of years (in revision, Proc Natl Acad Sci USA). He is confident that the wealth of molecular information and tools we possess today will “open the exciting possibility of watching evolution in action in the laboratory”. These works are perfect examples of how mammoth databases generated from such massive international scientific collaborations have limitless potential to help answer challenging scientific questions and, in the process, improve human lives and perhaps also contribute to preserving our ecosystem.
Echoing the optimistic sentiments of the renowned inventor and engineer, Charles Kettering, “there exist limitless opportunities in every industry. Where there is an open mind, there will always be a frontier”. Here‟s hoping that many more exciting new frontiers will be explored by our Fellows and other scientists all around the world together in harmony and with integrity.
M. Wilhelm et al., “Mass-spectrometry-based draft of the human proteome,” Nature, 2014. M.S. Kim et al. “A draft map of the human proteome,” Nature, 2014 Ramadas R, Thattai M. “New organelles by gene duplication in a biophysical model of eukaryote endomembrane evolution.” Biophys J. 2013 Human Proteome Map Human Protein Atlas Mouse Encode Consortium. Image source for Oswald Avery Colin MacLeod and Maclyn McCarty- National Medical Library, National Institutes of Health Image source for James D Watson and Francis Crick, First X-ray image of DNA, Marice Wilkin’s letter to Francis Crick Wellcome Images
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INDIA ALLIANCE STAFF CORNER
Megha Saraswat Sharma, Programme Manager Megha was one of the first personnel of the India Alliance team when it was established in 2009, and started her career here as a Grants Adviser. Ever since then she has grown and evolved with the organisation and today acts as the Programme Manager. She talks here about her India Alliance journey, general interests and what inspires her.
What is your background? I completed my PhD from National Institute of Nutrition, Hyderabad under the supervision of Dr G. Bhanuparkash Reddy, an eminent scholar in the field of eye research. My doctoral work was focused on studying one of the secondary complications of diabetes (Cataract). Joining the India Alliance in the year 2009 opened up new avenues in my career.
What do you enjoy most about working at the India Alliance? I was extremely fortunate to be part of the first team that was set up to implement the vision of bringing a radical change to Science funding in India. India Alliance has given me ample opportunities to learn and experience different aspects of Grants Management and related processes during this time. It gives me immense satisfaction to see an efficient Grant Management Team working diligently towards achieving the mandate of the programme. I thank all the members of the team for their sincere efforts in successfully handling their assignments. Our continued endeavour is to serve the nation in its drive to make India a better place for scientists to pursue their research aspirations.
What are your hobbies/interests? Music is my passion, I‟m fond of Indian classical music. At the community level, I try to help underprivileged children by my own small contribution and hope to bring a larger change in the lives of these children in future.
Who inspires you (living or dead)? I take inspiration from the mundane things of life. It can be a conversation with a friend, experiences of one‟s life and the fighting spirit of people I know of, around me, who are facing hardships. I particularly find inspiration from one book, which keeps the hope alive even in difficult times – which is “The Secret‟‟ by Rhonda Byrne. It shares amazing ways of maintaining a positive attitude and optimistic outlook in life, which are enough to keep one going.
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Descriptions of the images on the cover Drosophila Hematopoietic Organ: the Lymph Gland. The differentiating hemocytes populating the peripheral regions (Green and Blue) arise from the pluripotent stem like precursors (red), which forms the inner core of the gland. Lolitika Mandal, Intermediate Fellow Scanning electron micrograph of a zebrafish epidermis mutant gaensehaut (goose-bumps in English). Mahendra Sonawane, Senior Fellow The immuno-fluorescence image shows tumors (Green) due to loss of tumor suppressor Lgl on wing imaginal disc of Drosophila larva. Note that the domain which has acquired Vestigial (Red) to become the future adult wing is tumor free. Anjali Bajpai, Early Career Fellow The Dengue virus genome needs to replicate efficiently to sustain a viable infection cycle. The released genomic RNA is bound and copied by the RNA dependent RNA polymerase to generate the new viral RNA. Rahul Roy, Intermediate Fellow
Wellcome images
Location of pain fibers in the spinal cord
Confocal image of human embryo
Purkinje cell
Scanning electron micropgraph of red blood
Scanning electron micropgraph of a midge eye
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Wellcome Trust/DBT India Alliance is a public charitable trust registered in India