India Alliance Newsletter I Issue 1 I January 2015
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Transcript of India Alliance Newsletter I Issue 1 I January 2015
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
[email protected]. 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
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Wellcome Trust/DBT India Alliance is a public charitable trust registered in India