India Alliance Newsletter

News & ViewsIssue 1, January 2015

EDITORIAL

1.

“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

CONTENTS

2.

3 AN OVERVIEW OF INDIA ALLIANCE FELLOWSHIPS

4 CALL FOR IA FELLOWSHIP APPLICATIONS

Announcement for Clinical & Public Health and Research Training Fellowships

5 UPCOMING EVENTS & PUBLIC ENGAGEMENT

SciComm Hyderabad, SciComm101, Public Lecture series, Public Engagement

competition for fellows

8 IA FELLOW‟S RESEARCH HIGHLIGHTS

Featuring recent research articles of Neha Vyas, Urvakhsh Mehta, Arun Shukla,

Amit Singh, Mahendra Sonawane

11 VIEWPOINT

Harnessing mobile technology to provide basic health care in rural India

by Pallab Maulik, India Alliance Intermediate Fellow

14 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

15 FEATURE ARTICLE

From the Human Genome to Proteome – unraveling the puzzle, piece by piece

by Sarah Iqbal, India Alliance Public Engagement Officer

18 INDIA ALLIANCE STAFF CORNER

Megha Saraswat Sharma, Programme Manager

AN OVERVIEW

INDIA ALLIANCE FELLOWSHIPS

For further information please visit our website

Criteria Early Career Intermediate Senior Margdarshi

Eligibility(post-PhD/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

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.

3.

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

Clinicians‟ 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.

4.

UPCOMING EVENTS

SCIENCE COMMUNICATION WORKSHOPS

SciComm Hyderabad

In keeping with our mandate to empower future leaders of Indian science, the

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.

20-21 March,

2015

20-21 March, 2015

Hyderabad

SciComm101

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 it‟s launch in March 2014.

The next SciComm101 is scheduled to be held at IIT Kanpur on 23

January 2015.

23 Jan, 2015

IIT Kanpur

For more details visit "Scicomm Workshop" under "Quick Links" on our website

5.

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 Avery‟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.

6.

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 DharaviBiennale” is an art and health festival to bring local artists, the community in Dharaviand health researchers together to create artistic pieces and explore issues in urban health.” Photo and text credits: Dharavi Biennale, Wellcome Trust, UK

7.

Vesicular Sonic Hedgehog: Companions matter

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

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

Mirrors in the mind

Urvakhsh Mehta, Early Career Fellow

NIMHANS, Bangalore

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 self-

monitoring 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

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

8.

Neha Vyas, Early Career Fellow

inStem, Bangalore

“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

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.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

9.

AWARD: Amit Singh has been awarded senior Innovative Young Biotechnologist Award(IYBA)

by Department of Biotechnology, India.

INDIA ALLIANCE

RESEARCH HIGHLIGHTS

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).

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

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

Irregular cell shape and size in Myosin Vb

deficient embryos compared to wild-type

Model showing the regulation of epithelial patterning in

zebrafish fin-fold epithelium by the canonical Wnt signalling

gradient

New insights into the mechanisms involved

in the maintenance of epidermal integrity

in zebrafish

Mahendra Sonawane, Senior Fellow

TIFR, Mumbai

10.

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

facilities in our rural sector.

Typical village setting from the area where George

Institute, Hyderabad, is testing its mobile based clinical

decision support tools

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

11.

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.

VIEWPOINTHarnessing mobile technology to provide basic health care in rural India

12.

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.

VIEWPOINTHarnessing mobile technology to provide basic health care in rural India

13.

IN CONVERSATION WITH..

Prof Nadrian Seeman

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.

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.

14.

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

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

FEATURE ARTICLE

From the Human Genome to Proteome –

unraveling the puzzle, piece by piece

Sarah Iqbal,

India Alliance

Maurice Wilkin‟s letter to Francis Crick

Oswald Avery Colin MacLeod and Maclyn McCarty

Francis Crick & James D Watson

"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

First X-ray image of the DNA

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

dawn of innovative and groundbreaking research strategies that kick-

started 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

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‟

15.

FEATURE ARTICLEFrom the Human Genome to Proteome – unraveling the puzzle, piece by piece

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.

Harsha Gowda

16.

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,

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

Mukund Thattai

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

analysis of genetic maps of various organisms and cell biological

FEATURE ARTICLEFrom the Human Genome to Proteome – unraveling the puzzle, piece by piece

17.

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.

18.

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.

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.

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

Wellcome Trust/DBT India Alliance is a public charitable trust registered in India

Please send your feedback, suggestions and contributions to

public.engagement@wellcomedbt.org

Follow us on

Wellcome Trust/DBT India Alliance is a public charitable trust registered in India