india alliance newsletter i issue 6 i november 2015
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The Wellcome Trust/DBT India Alliance Bimonthly Newsletter. Download the pdf by clicking on share.TRANSCRIPT
News & Views Issue 6, November 2015
INDIA ALLIANCE
Science cannot be divided into what is up to date and what is merely of antiquarian interest; it is to be regarded as the
product of a growth of thought- Peter B. Medawar
As the year draws to a close, our last newsletter issue of 2015 brings to you the latest round up on news of our Fellowship
schemes, updates on our Fellow’s research, public engagement and science communication activities along with some
interesting interviews and outreach initiatives . Our Annual Report of the year 2014-15 can be viewed here.
On the Fellowships front, all our fellowship competitions are presently closed and the submitted applications for Early
Career Fellowships and Senior and Intermediate Fellowships (basic scheme) are under review. Interview for Clinical and
Public Health fellowships, Research Training Fellowships, Margdarshi Fellowships and Senior and Intermediate Fellowships
(basic research scheme) were held in the first week of November in Hyderabad, results of which will be announced
shortly. The 12th two-day Science Communication workshop held in Hyderabad on 14-15 September, was shortly followed
by a one-day sciComm101 workshop at Vinayaka Missions University, Salem, Tamil Nadu on 21 September which was
attended by around 80 PhD students and young researchers. As part of public engagement exercise, our Fellows sent
wonderful entries for our first ‘Research Image Competition’, the results of which can be found in this issue.
In this issue, we feature recently published work of our Fellows, Drs Benu Brata Das, Rakesh K Laishram, Thomas
Pucadyil, Vatsala Thirumalai & R Mahalakshmi. Recognising and echoing the importance of the ‘World Antibiotic
Awareness Week’ that starts today, the feature article “Emergence of a new Resistance” describes the emerging crisis of
Antimicrobial Resistance, one of the biggest threats to global health today. Our Intermediate Fellow at IGIB, New Delhi, Dr
Sheetal Gandotra, shares with us the impact of her current research on Mycobacterium Tuberculosis, role of scientists and
science in India and much more, in the ‘Fellow in the Spotlight’ section. Last but not the least, our Grants Adviser, Dr
Ranjana Sarma reminisces about her early childhood and research days, recounts how India Alliance experience has been
a mixed bag, her love for martial arts and dance, in the ‘IA Staff Corner’ section
My heartfelt gratitude goes out to all the contributors for this issue. A special thanks to Drs Bushra Ateeq and Anjali
Bajpai, for the cover image.
We will continue to bring to you interesting scientific discoveries and discussions in the new year and as always look
forward to your comments and suggestions.
Best wishes,
Dr Sarah Iqbal Public Engagement Officer
EDITORIAL
1.
CONTENTS
3 INDIA ALLIANCE OUTREACH EVENTS
5 INDIA ALLIANCE SCIENCE COMMUNICATION WORKSHOPS
SciComm Hyderabad September 2015, SciComm101 Salem
7 INDIA ALLIANCE PUBLIC ENGAGEMENT CORNER
Research Image Competition for Fellows
8 INDIA ALLIANCE RESEARCH HIGHLIGHTS
Featuring recent research articles by Fellows, Drs Benu Brata Das, Rakesh K
Laishram, Thomas Pucadyil, Vatsala Thirumalai & R Mahalakshmi
11 INDIA ALLIANCE FELLOW IN SPOTLIGHT
Dr Sheetal Gandotra, Intermediate Fellow, IGIB, New Delhi
12 FEATURE ARTICLE
Emergence of a new Resistance
by Dr Sarah Iqbal, Public Engagement officer, India Alliance
15 INDIA ALLIANCE STAFF CORNER
Dr Ranjana Sarma, Grants Adviser, India Alliance
2.
INDIA ALLIANCE
6TH ANNUAL FELLOW’S MEETING
The Wellcome Trust/DBT India Alliance hosted its two-day Annual Fellow’s Meeting on 5-6th November 2015 at Novotel Hotel, Hyderabad. This meeting brought together 100 of its
Fellows from around 50 institutions across India, along with Wellcome Trust officers and about 30 eminent Indian and international scientists from University of Oxford, London School of Hygiene and Tropical Medicine, University of Oxford, University of California, USA, University of North Texas Health Science Center, USA, Johns Hopkins University, USA, University of Leeds, University of Dundee, UK and Institute of Molecular, Cell Biology, Portugal, University College of London, National Institute of Medical Research, UK and MRC National Institute of Medical Research, UK. Two representatives from the African Academy of Sciences also participated in this two-day event to understand the operations of the India Alliance as they prepare for a similar partnership with the Wellcome Trust, UK, in Africa. The scientific research presented at the meeting was on themes ranging from genomics, cancer, neuroscience to
nutrition, stem cell research and many other areas of biomedical research. Apart from the scientific presentations, there were talks and discussions on various facets of scientific
research in India. Dr Simon Kay, International operations, Wellcome Trust, UK, discussed the importance of diversity in science and urged the scientists in the audience to maintain and respect diversity in their workplaces. Renowned Indian scientist, Prof D Balasubramanian (LVPEI, Hyderabad) encouraged the scientists in attendance to talk about their science to the public and explained the significance of this engagement. As part of a public engagement exercise, the two-day event also included a display of research images by the Fellows, which were judged for their visual impact, context and its understandability for a public audience. There were many interactive sessions throughout the two days which showcased and discussed the research funded by the Wellcome Trust/DBT India Alliance.
3.
INDIA ALLIANCE
OUTREACH EVENTS Life Science opportunities in India: A special session at The EMBO Meeting 2015 7 September, 2015 India Alliance along with IndiaBioscience participated in The EMBO meeting 2015 from 5-8 September, 2015 in Birmingham, UK. The Wellcome Trust/DBT India Alliance had also sponsored travel awards for 6 young scientists from India to attend the EMBO meeting. India Alliance and IndiaBioscience had a
booth on all days of the conference. There were questions asked about opportunities in India, how to apply and also to get an overall picture of science in India. In addition to Dr Jameel and Professor Noel Buckley (IA Senior and Intermediate Fellowship committee member & scientist at University of Oxford) representatives from EMBO and DBT were also present. From DBT there was Suman Govil and Meenaskhi Munshi. Participants were also able to interact with invited speakers at the booth. Around 30 people attended the special session on India. The speakers included Drs Shahid Jameel, LS Shashidhara, S Ramaswamy, Suman Govil, Meenakshi Munshi and Anne- Marie Glynn (EMBO).
INDIA ALLIANCE
OUTREACH EVENTS
4.
Young Investigators Meeting (YIM), UK 9 September, 2015 This event was organized at the Deakin Center, Cambridge, UK. Nearly 130 people registered for the event. There was a full day of talks from representatives of Indian Science, funding agencies and industry. The meeting concluded with a talk by Dr Vijayraghavan which was given by video conferencing. After the talks 20-25 graduate students and post-docs presented their work in a poster session. The delegates were highly enthusiastic and there was a great deal of interaction at the event. In addition to talks given by funding agencies, there were also different agencies seated at various tables. Participants were encouraged to approach them for further discussions. The Department of Biotechnology, the Wellcome Trust/DBT India Alliance, EMBO and Euraxess Links UK were some of the funding agencies represented at this event.
National Institutes of Health Research Festival September 17-18, 2015
The India Alliance in collaboration with IndiaBioscience had a stall at the NIH
Career Fair and Exhibition. Thousands of researchers working on various NIH campuses visited the booth. Researchers of both Indian origin and otherwise requested information about life sciences research in India and were particularly interested in the activities of India Alliance. There was a lively discourse about the opportunities and challenges of doing science in India.
Opportunities, challenges and impact of clinical health research in India 4 November 2015 The India Alliance and Krishna Institute of Medical Sciences (KIMS), Secunderabad, jointly organized a one-day symposium on 4th November 2015 at KIMS to discuss opportunities, challenges and impact of clinical and public health research. The symposium was divided into four sessions and concluded with a panel discussion, on themes ranging from genomics, neuroscience, urban health, health economics to funding opportunities and research challenges in
clinical and public health research in India. After the opening address and inauguration by Prof Kakarla Subba Rao, Chairman, KIMS Foundation & Research Centre and Dr Bhaskar Rao, CEO KIMS, eminent geneticist, Prof Arvinda Chakravarti chaired the plenary lecture by renowned Indian scientist Prof D Balasubramanian, LVPEI, Hyderabad. Dr Balasubramanian‟s talk described the opportunities for clinicians in areas of translational and clinical research and innovative methods to deliver healthcare from bench to bedside and vice-a-versa. The plenary lecture was followed by four sessions, where eminent clinician and clinical researchers talked about various clinical research fields. The distinguished line up of speakers comprised of Wellcome Trust/DBT India Alliance Committee members, Dr Aravinda Chakrabarti, Johns Hopkins, USA, Prof David Osrin, University of College, UK, Prof Sukhwinder Shergill, King‟s College London, UK, Prof Kara Hanson, London School of Hygiene and Tropical Medicine, London, UK, Prof Shinjini Bhatnagar, Translational Health Science & Technology Institute, Gurgaon, in addition to various other prominent local clinicians, Dr Aswin Dalal, CDFD, Dr Annie Hasan, Kamineni Institute of Medical Sciences, Dr Amitava Ray, Apollo Multispeciality Hospital and Dr Rakesh Sahay, Osmania Medical College and The sessions were chaired by Dr Sree Bhushan Raju, NIMS, Dr Sita Jayalakshmi, KIMS and Dr Kondagunta Nagaraj, Kamineni Institute of Medical Science, Hyderabad. India Alliance Fellows, Dr Arun Shet, Dr Muralidhara Nagarjuna, Dr Srinivas Marmamula and Dr Rupjyoti Talukadar were also present at the symposium and shared their India Alliance experience and views on clinical research in India. A strong call for more collaboration between basic science researchers and clinicians was made at this symposium.
INDIA ALLIANCE
SCIENCE COMMUNICATION WORKSHOPS
Participants and mentors of SciComm Hyderabad, September 2015
Empowering the communicators in young researchers
The 12th Science Communication workshop was held at the
Daspalla Hotel in Hyderabad from 14-15 September 2015 which
was attended by 34 PhD students, Postdocs, junior Faculty and
Clinicians from 29 different institutions across India such as, IISER
Trivandrum, Central Food Technological Research Institute,
Mysore, Centre for DNA Fingerprinting and Diagnostics,
Hyderabad, Indian Institute of Science, Education and
Research, Kolkata, DAPM RV Dental College and Hospital, IIT
Bombay, Christian Medical College, Vellore, Shiv Nadar
University, Greater Noida, Mysore Medical College and
Research Institute, Mysore, CSIR- Centre for Cellular and
Molecular Biology, Hyderabad, National Centre for Cell Science
(NCCS), Pune, National Institute of Mental Health and
Neurosciences, Bangalore, Indian Institute of Advanced
Research, Gandhinagar, BITS-Pilani, Hyderabad Campus,
ACTREC, Mumbai, Indian Institute of Science Bangalore, Indian
Institute of Chemical Technology Hyderabad, , Institute of
Bioinformatics and Applied Biotechnology (IBAB), Bangalore,
CSIR-Centre for Cellular and Molecular Biology, Hyderabad,
Amity University, New Delhi, Institute Of Medical Sciences,
Banaras Hindu University, All India Institute of Medical Sciences,
New Delhi, Acharya Nagarjuna University, Guntur, University of
Mysore, Defence Institute of Physiology and Allied Sciences
(DIPAS), DRDO, New Delhi, CSIR-Central Drug Research Institute,
School of Life Sciences, Manipal and Pondicherry University.
The first day of the workshop focused on oral presentation
skills and important elements of an effective professional
presentation. This session was conducted by Mrs Sumathy
Haridas, an HR consultant from Bangalore, who gave useful
advice on how to prepare the message of a presentation,
appear confident, speak articulately and engage the
audience. Her session consisted of various hands-on exercises
for the participants that ensured active participation. Following
this session, India Alliance Public Engagement officer, Dr Sarah
Iqbal encouraged the participants to deliberate on the topic of
Public Engagement with Science and in what ways, as scientists
and clinicians, they could take their research to the public and
collaborate with them to get fresher research perspectives. She
also initiated an interesting discussion on what ails productive
communication between the clinicians and basic research
community in India. Grants Adviser, Dr Madhankumar
Anandhakrishnan concluded the first day by giving a brief
overview of the India Alliance Fellowship schemes and
application process. The participants discussed various issues
concerning the workshop, career choices and their current
research with the India Alliance staff and the workshop mentors
over the Networking dinner.
The second day of the workshop covered topics such as,
Ethics in Research, Clinical research, Grant and Manuscript
writing, talks on which were given by Dr Anant Bhan (Yenepoya
University, Mangalore), Dr Anurag Agrawal (IGIB, New Delhi), Dr
Lolitika Mandal (IISER Mohali), Dr Mahak Sharma (IISER Mohali)
and Prof Sandhya Visweswariah (IISc Bangalore). The Mentors
stimulated various discussions on these topics and ensured the
participants were not wary of asking important questions about
research career development, setting up a lab, postdoc
opportunities, clinical research and many more. The highlight of
the workshop for the participants was the research proposal
discussion, where participants received useful feedback and
advice on the structure and content of their proposals from the
mentors.
The enthusiasm and active questioning at the workshop by
the participants reinforced the importance of Science
Communication in nurturing and training the future researchers
of India.
Watch this space for the announcement of the next two-day SciComm workshop and other communication training initiatives
5.
One-day SciComm101 workshop at Vinayaka Missions University
Salem, Tamil Nadu
INDIA ALLIANCE
SCIENCE COMMUNICATION WORKSHOPS
Few of our current Fellows had attended the two-day SciComm Hyderabad workshop before they applied for the IA Fellowships which were eventually awarded to them. Three of them share their thoughts here on how the training helped them to write successful grant applications and their general experience of the workshop.
SciComm Hyderabad 2011 The things that I expected, including a comprehensive overview of Early Career Fellowships, scientific presentation skills, went as expected. Most important aspect of the SciComm for me was the discussion session with the mentor. I was planning to change my research field from cellular immunology to the molecular biology of learning and memory. Based on my short research proposal (which eventually became my ECF proposal) I was grouped with students having somewhat overlapping research interests. The mentor we had during the SciComm workshop was an eminent neuroscientist from India. It was the first time that I had any discussion on merits and shortcomings of my research proposal with the expert in the field. The discussions later proved to be extremely valuable.
Dr Yogesh Dahiya, Early Career Fellow, IISER Mohali
SciComm Hyderabad 2013 The workshop has been a catalyst in honing my grantsmanship skills. It was a very well crafted workshop by the India alliance team. The sessions were engaging and focused. The session on the live recording of presentations proved to be very productive. Interacting with peer scientists was enjoyable; the richness of shared experiences was a great way to learn. Thanks to this opportunity, I was able to successfully apply the learning into accomplishing the award of intermediate fellowship. I highly
recommend to any young public health researcher to attend this workshop for enhancing the skills in scientific communication.
Dr Giridhara R Babu, Intermediate Fellow, Public Health Foundation of India
SciComm Hyderabad 2014
I found the workshop to be extremely useful to improve grant applications. Since I was also applying for the Wellcome Trust/DBT India Alliance ECF, the interactions with mentors on my dummy project were invaluable. These helped me critically evaluate my application and frame it better. In general, the workshop was an extremely well-planned and balanced for instilling presentation and scientific skills. The sessions on body-language and communication were eye-openers and helpful for any competitive grant procedure.
Dr Tavpritesh Sethi, Early Career Fellow, AIIMS, New Delhi
From a SciComm participant to an IA Fellow
India Alliance‟s SciComm101 workshop team reached the
steel city of Salem, Tamil Nadu, on 21 September 2015. The
workshop was held at the Vinayaka Missions University and was
attended by around 80 research scholars and young scientists
of various departments of the university along with participants
from institutions such as, Kongu Engineering College, Perundurai,
JSS College of Pharmacy, Ooty, K.S.R.College of Technology,
Tiruchengode, Velalar College of Engineering & Technology,
Erode, Bharathiyar University, Coimbatore, Mahendra College of
Engineering, Namakkal, Padmavani Arts and Science College
for Women, Salem, Periyar University, Salem, Kerala Agricultural
University, Thrissur, Kerala, Tamil Nadu Agricultural University,
Mahendra Arts and Science College, Salem, Sri Vijay Vidyalaya
College of Arts and Science, J.K.K Nattraja College of
Pharmacy, Government Mohan Kumaramangalam Medical
College, Salem, Vivekananda College of Arts and Science,
Tiruchengode, Sivaraj Siddha Medical College.
In addition to the life sciences streams, the workshop
participants came from varied backgrounds, such as nursing,
biomedical and electrical engineering, architecture, dental
science, chemistry and physics. The attendees particularly
appreciated the interactive nature of the sessions and for the
opportunity of receiving this unique training which is not
available to most of them in their respective institutions.
6.
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
As part of a public engagement exercise, the India Alliance launched its first „Research Image Competition‟ for its Fellows last month. The entries included photographs, microscopy images and illustrations which conveyed a scientific principle and/or a relevant human health perspective. The
images were judged on visual impact, context and their understandability for a public audience. Top three prizes were given to the following images.
7.
INTRICATE ARRANGEMENT OF DIVERSE CELL TYPES IN THE GUT OF A FRUIT FLY
By DR BUSHRA ATEEQ, Intermediate Fel low& DR ANJALI BAJPAI, Ear ly Career Fel low O th e r I mage C r e ato r s : Ms Uma n s h i R a u te l a , P r o f P r a d ip S i n h a
The image shows intricate arrangement of the various
cell types in the mid-gut region of a genetically
modified fruit fly. White/grey colored striated lines
depict gut musculature, rosette shaped white/grey
structures are large copper cells with red nucleus in the
center; small green colored structures are stem cells of
the gut. *This is also the cover image
THE CANCER
By DR SANJAY CHILBULE, Research T ra ining Fel low
Newly formed cancer cells of bone cancer are spreading out
centrifugally from their parent cells which probably may be happening inside the body.
WE CARE, FOR EYE CARE, EVERYWHERE
By DR SRINIVAS MARMAMULA, Research T ra ining Fel low
Vision loss is more commonly in elderly people in rural areas, even more
common among women. This image shows a vision technician assessing
vision in a woman in a village in Telangana as a part of public health
research project undertaken by L V Prasad Eye Institute, India.
Dr Sheetal Gandotra is a Wellcome Trust/DBT Intermediate Fellow at the Institute of Genomics and Integrative Biology (IGIB), New Delhi. Sheetal is using various genetic and cellular tools to understand the survival and infectious mechanisms of Mycobacterium tuberculosis (Mtb). In this interview, she shares with us the impact of her current research, role of scientists and science in India and much more..
INDIA ALLIANCE FELLOW SPOTLIGHT
DR SHEETAL GANDOTRA Intermediate Fellow, IGIB, New Delhi
What are you working on and what impact do you hope it will have?
Tuberculosis disease pathology has had a long standing link
with lipids- be it the virulence imparting lipids of the bacterium
Mycobacterium tuberculosis or the host lipids that accumulate in
the granuloma. We are working on identifying mechanism(s)
whereby the intracellular bacilli alter the host cell‟s lipid storage
depots -the lipid droplets, such that the characteristic lipid loaded
foamy macrophages develop and at the same time the bacilli
make use of fatty acids from the host cell. By addressing the first
question we hope to be able to understand the metabolic link
between the innate immune response and disease pathology.
The second question is fundamental to understanding how lipids
are mobilized from an organelle of the host to the bacilli, across
several membrane barriers. We hope that this will lead to
identifying targets that will limit the ability of bacteria to scavenge
nutrients from the host cell- in essence, we want to bite the hand
that feeds the devil.
What inspired you to become a scientist?
My teachers- Mrs Nandita Narainswamy, Dr Anil Tyagi, Dr Debi
Sarkar, Dr Carl Nathan, and the late Dr Alan Houghton have been
the most instrumental in driving me towards research. Their
undying love for their subjects and their ability to infuse that
excitement through their classes left me with more questions and
encouraged me to ask those questions. Mentoring by researchers
like Dr Sabine Ehrt and Dr Dirk Schnappinger encouraged me to
be fearless in approaching larger questions. I think I am still
learning every day on how to really become a scientist because
that is so much more than simply “doing science”. There is so
much to learn in terms of managing a lab and a team and I think
I grow a little bit with every student that joins my group or
engages me in their questions. In a way, their questions inspire me
further. Last but not the least, the pathogen I work on-
Mycobacterium tuberculosis continues to challenge me and that
really is the basis of what I work on.
How do you think scientists and scientific research can offer solutions to India's problems today?
Science and reasoning is the only way out of the several socio-
economic problems that deeply affect the growth of India. While we
hope that the basic research we carry out in our lab is able to offer
new sustainable solutions to tuberculosis treatment, we do realize that
by inspiring more people in our neighbourhood, in our city, and in the
country, towards logic, reasoning, and high quality research, the
scientific community holds great responsibility in bringing about this
positive change.
How has Wellcome Trust/DBT India Alliance funding helped you and your research?
When I moved back to India, I knew what I wanted to work on but
understood the difficulties and challenges of the questions I was
asking. Applying to the Wellcome Trust/DBT India Alliance in itself was
a means to put these ideas on track and focus on a few of these
questions. The award has allowed me to take on a high risk project
but also cautioned me and advised me through the reviews about
how I should manouver through the challenges. This is equally
important to the generous consumable, equipment, and travel
support that comes with the award. Research in a biosafety
laboratory conditions for a slow growing organism like M. tuberculosis
is not only time consumingbut extremely expensive, with specialized
equipments dedicated for the facility. The generous funding from this
award has helped me establish some of these key aspects of my
research.
What keeps you going everyday?
This really depends on the situation and my surroundings. During my
PhD I started learning Bharatanatyam; I would travel 3 hours from
Manhattan to Queens for a 1 hour class. In the UK, I became an avid
gym fan, and since moving back to India, I think it is the support of
family that keeps me going. I like to paint and experiment with my
creative abilities- be it a wall or a window pane at home. While I get
little time to do such things, the build up to a creative pursuit is equally
important to me.
8.
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
DNA Topoisomerase 1 (Top1) is an essential enzyme for
expediting the release of torsional stress generated during
various DNA transactions. Top1 is expressed much higher in
various tumour cells than the normal cells, therefore,
modulating the Top1 levels could be an important therapeutic
treatment for cancer. Top1 when trapped on the DNA as
Top1-DNA covalent complexes (Top1cc) by anticancer drug
camptothecin (CPT) or its clinical derivatives leads to DNA
double-strand breaks, which results in death of malignant
cancer cells. In our published study, we looked at another
class of compounds known as „hydantoins‟, which have
received much attention in the last decade or so for having
anti-cancer properties. We designed and synthesized a library
comprising of hydantoin and thiohydantoin derivatives and
tested them against human Top1. One of the thiohydantoin
compounds with substituted thiophenyl as the central moiety
exhibited potent inhibition of Top1 through stabilization of
Top1cc as shown by its anti-cancer activity against human
cervical carcinoma (HeLa) and breast carcinoma (MCF-7)
cells. These results suggest that the selected thiohydantoin
may be a suitable lead to develop as potential anti-cancer
compound.
Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity. Majumdar P, Bathula C, Basu SM, Das SK, Agarwal R, Hati S, Singh A, Sen S, Das BB*. 2015; Eur J Med Chem. 102:540-51. Image above: Molecular docking for the anti-cancer compound in a
ternary complex with DNA and human Topoisomerase 1 rationalized the
inhibitory mechanism of the compound (Red). Indicated amino acids
showing the plausible architecture of the active site of Human Top1
interacting with compound. The computational study provides insight to
the structure activity relationship of the compound to gain Top1
inhibitory activity.
Novel anti-cancer compound targeting DNA cutting enzyme, Topoisomerase I DR BENU BRATA DAS, Intermediate Fellow, Indian Association for the Cultivation of Science, Kolkata
Targeting the right messenger RNA Mechanism of poly(A) polymerase specificity
DR RAKESH SINGH LAISHRAM, Intermediate Fellow, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram
Gene expression in humans involves multiple steps: from
messenger RNA (m RNA) synthesis in the nucleus to translation
in the cytoplasm. 3‟-end RNA processing is an essential step in
mRNA synthesis that involves addition of a polyadenosine (A)
tail at the 3‟- untranslated region (UTR) by enzyme called
poly(A) polymerase (PAP). Poly(A) tail is essential for stability
and efficient translation of the mRNA. There are two major
poly(A) polymerases involved in general polyadenylation in
the nucleus - canonical PAPα and Star-PAP. The two PAPs
have distinct niche of target mRNAs and are independent of
each other. Yet, how the two PAPs select their respective
target mRNAs is not understood. Using Star-PAP as an
example, we established the mechanism of PAP specificity
where Star-PAP recognizes a distinct sequence element at the
trailing 3‟–UTR and excludes PAPα from the UTR. There are two
aspects of PAP specificity – recognition of target mRNA and
exclusion of the other PAP, rendering the mRNA to exclusive
control of one PAP. We identified Star-PAP recognition motif
(AUA) on the mRNA target upstream of poly(A) site.
9.
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Moreover, lack of the polyadenylation factor, CstF-64,
binding prevents PAPα from accessing Star-PAP target
mRNA.
Altering the 3‟-UTR cis-element on Star-PAP target mRNA
switches the regulatory PAP from Star-PAP to PAPα. Both the
PAPs also compete with each other for binding to mRNA
cleavage factor, CPSF but with a preference to Star-PAP
suggesting preferential use of Star-PAP regulated sites. This
specificity regulates alternative polyadenylation and PAP
switch at the 3‟-UTR.
CstF-64 and 3'UTR cis-element determine Star-PAP
specificity for target mRNA selection by excluding PAPα. Kandala DT, Mohan N, A V, Ap S, G R, Laishram RS. 2015 Nucleic Acid Research
Ever wonder how you keep your balance? This is
something that we learn to do as toddlers, and it involves the
coordinated effort of various muscles in the body. An area at
the base of the brain called the cerebellum controls this effort,
and synchronizes our muscles by sending messages in the form
of electrical signals along cells called Purkinje neurons. These
signals consist of steady „tonic‟ activity or short „bursts‟ of
activity. Previous studies in unconscious mammals suggest that
these neurons can spontaneously switch between the two
types of electrical signals.
However, it is not clear whether this switch occurs in awake
animals, or how these nerve activities control muscle
movements. It is technically challenging to record the voltage
of single Purkinje neurons of conscious rodents, so this problem
was avoided by using zebrafish larvae instead. These larvae
are small, transparent and lack a skull, which makes it possible
to record the activity of the cerebellum using tiny glass
electrodes. The experiments show that even when the larvae
are awake, the Purkinje cells produce either spontaneous
bursts or tonic activity and they can readily switch between
the two. The switch is controlled in part by the voltage on the
neurons' surface. A positive voltage is called the „up‟ state,
while a negative voltage is dubbed the „down‟ state. Neurons
in the „up‟ state produced tonic pulses, while neurons in the
„down‟ state produced short bursts of activity with the help of
an ion channel called AMPAR.
Cells called motor neurons in the spinal cord carry the final
command from the nervous system to the muscles. We
recorded the activity of motor neurons and Purkinje neurons
at the same time. This revealed that Purkinje neurons receive
a copy of the motor command that goes to the muscle and
produce short bursts of electrical activity in response. This
effect required AMPAR activity, and was blocked by
molecules that inhibit AMPAR. Furthermore, the timing of these
short bursts with respect to the motor command changes from
one Purkinje neuron to another. Future work will investigate
how the Purkinje neurons receive and process the information
in the motor command.
AMPA receptor mediated synaptic excitation drives state-dependent bursting in Purkinje neurons of zebrafish larvae Mohini Sengupta, Vatsala Thirumalai. eLife Image above: Pseudocolor images of Purkinje neurons in adult zebrafish cerebellum. Image created by Lena Robra and Mohini Sengupta
10.
Unique Nerve Activity in the Cerebellum
DR VATSALA THIRUMALAI, Intermediate Fellow, NCBS, Bangalore
Structural insights into the channels of the mitochondria
DR R MAHALAKSHMI, Intermediate Fellow, IISER Bhopal
Voltage-dependent anion channels, or VDACs, are pore-
forming outer mitochondrial membrane proteins that help
govern cellular homeostasis. These are 19-stranded
transmembrane β-barrel proteins (as shown in the image
above) that shuttle various products of the metabolic process
between the cytoplasm and mitochondria in a cell. Of the
three isoforms (-1, -2 and -3) of VDACs in humans, hVDAC-2 is
more important for cell survival. Current understanding of the
structure-function relationship of anti-apoptotic hVDAC-2 is still
at its inception. It has a unique 11-residue stretch at the N-
terminal helix and an unusually high cysteine content. In this
study, we have examined the role of the N-helix and cysteines
on the structure and function of this important channel. Our
findings highlight the unique and hitherto unknown
interdependent contribution of the N-helix and cysteine
residues to the function, barrel folding and stability of hVDAC-
2. Our work is an important advancement in understanding
hVDAC-2 barrel dynamics and provides insight into factors
that functionally demarcate this protein from the other
VDACs. Our work will help us understand the important role
played by the hVDAC-2 protein in deciding the fate of the
cell. We also demonstrate the evolutionary relevance of the
N-terminal 11-residues of hVDAC-2 in the context of cysteine
conservation.
N-helix and cysteines inter-regulate human mitochondrial VDAC-2 function and biochemistry. Svetlana Rajkumar Maurya and Radhakrishnan Mahalakshmi. The Journal of Biological Chemistry
A high throughput platform to study cell membrane fission DR THOMAS PUCADYIL, Intermediate Fellow, IISER Pune
Cell membrane fission requires the localized application of
curvature stresses to the lipid bilayer in order for a membrane
tube to go from a highly constricted to a cut state. Since
these topological transformations require the bilayer to
deviate from its preferred planar configuration, membrane
fission is an energetically unfavorable process. The GTPase
dynamin represent a group of specialized protein machines
that catalyze membrane fission. Dynamin manages this
process by self-assembling into a helical scaffold that
hydrolyzes GTP to constrict and cut the underlying membrane
tube. How it does it has been a subject of intense controversy.
Membrane fission reactions are carried out in a confined
region of the membrane enclosed within a 10 nm wide, 2-rung
scaffold comprised of ~26 molecules of dynamin. Thus, the
changes in shape of the underlying membrane tube have
been difficult to probe. Our team has now devised a novel
model membrane system comprised of narrow membrane
tubes laid on a non-reactive glass surface, which they call
supported membrane tubes or SMrTs. Membrane tubes
represent an ideal mimic of the necks of clathrin-coated pits,
the physiological substrate upon which dynamin is thought to
act in cells. Since the tubes are stably laid out on a glass
surface, one can now use conventional wide field
microscopic approaches to locally probe changes in
membrane shape during a single dynamin-catalyzed fission
event. Indeed, results from such experiments reveal the
necessity for GTP hydrolysis during dynamin-catalyzed
membrane fission. Dynamin self-assembly into a helical
scaffold constricts the underlying tube but does so to a
moderate extent. GTP hydrolysis is required for further
constricting the underlying tube for it to reach dimensions
necessary for fission.
A high-throughput platform for real-time analysis of membrane fission reactions reveals dynamin function. Srishti Dar, Sukrut Kamerkar and Thomas Pucadyil. Nature Cell Biology.
11.
FEATURE ARTICLE
EMERGENCE OF A NEW RESISTANCE DR SARAH IQBAL, PUBLIC ENGAGEMENT OFFICER, INDIA ALLIANCE
12.
The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the
ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug
make them resistant. Alexander Fleming, Nobel Lecture, 1945, inventor of Penicillin
This year‟s Noble prize in Medicine and Physiology,
applauding the discoveries concerning novel therapies
against infections, is in grim contrast to global health
epidemic of antimicrobial resistance (AMR) that the world is
facing today. AMR has fast become an obstacle in the
prevention and treatment of variety of infections caused by
bugs such as bacteria, parasites, viruses and fungi, which
cause HIV, influenza, malaria, tuberculosis and host of other
infections. Not paying heed to the „words of caution‟ of the
inventor of the first legitimate antibiotic has led us towards a
major public health crisis world-wide, which could become
more severe in the less developed regions, where infections
are rampant and healthcare services abysmal.
AMR can be loosely defined as resistance of the infectious
bugs against the medications used to eliminate them, by
overpowering its toxic effects. A bug or a microbe acquires
resistance through modifications in its genes- an important
illustration of Darwin‟s natural selection. For instance,
antibiotics work through inactivating proteins in the bacteria
thereby shutting down its growth machinery. Any genetic
change in the protein can prevent the antibiotic to do its
work effectively. Alternatively, the genetic modification could
lead to an increased production of the antibiotic‟s target
protein, which makes the drug ineffective in inactivating all of
that protein. Adding to the existing molecular complexities,
the bacterial evolutionary survival mechanisms enable these
microorganisms to literally borrow genes from one another.
This further leads to the spread of resistant genes in the
bacterial population.
Let us zoom out of the bacterial cell and describe the
possible causes that can lead to AMR. If a recommended
drug is not used for the time necessary for eliminating the
infection, it kills a small population of infection-causing
microbes but the remaining population could become
resistant to this medication and keep growing. Additionally,
there is a collateral consequence of using an antimicrobial-
the drug not only removes the infectious microbes but also
some of the healthy ones, which leads to the infectious and
resistant microbes to take over the body. This is the reason
why the doctor strictly instructs us to finish the course of the
prescribed antibiotic even if we feel better after the first few
doses. It has also been observed that low-level of exposure to
certain antibiotics leads to increased incidence of mutations,
non-reproductive gene transfer between bacteria and
consequently a higher likelihood of the bacterial populations
to acquire resistance.
Let us now zoom into one of the biggest centres of this
epidemic with highest users of antibiotics and explore social,
environmental and medical factors which are giving rise to
AMR. Even though the global report by WHO on AMR in 2014
indicates that AMR crisis is present in every region of the
world, its health and economic consequences in a middle
income country such as India could be very damaging and
long-lasting. In nearly every corner of India where one has
access to medicines, antibiotics are given to young children
and adults alike, in an unsupervised and reckless manner.
Easy over-the-counter availability, irresponsible clinical
conduct and strong insistence by patients for antibiotics for
even minor infections, are some of the major factors leading
to high use of this medication in India. For a lot of Indians,
staying home to recover from infections can cost a job and
taking the wrong drug (for e.g, an antibiotic for a viral
infection) can prolong sickness. According to a report by
Center for Disease Dynamics, Economics and Policy, that
surveyed antibiotic use and AMR incidence in 69 countries
including India, suggests that globally 80% of antibiotics are
used outside the hospital where there is very little supervision.
Wellcome Library, London
13.
FEATURE ARTICLE
EMERGENCE OF A NEW RESISTANCE
India was the highest consumer of antibiotics according to a
survey done in 2010, using up to 13 billion Standard Unit (SU)
of antibiotics compared to 7 billion in USA. This unregulated
sale and over-prescription of antibiotics is one of the primary
causes of AMR cases in India. Poor sanitation and
widespread malnutrition in the country only augments the
AMR-related disease burden. Resistance developed due to
nonmedical consumption mainly results from its use as
veterinary medicine, growth-promoters in livestock and in
agriculture. This type of use, however, is not as high in India in
comparison to other countries that are heavy-consumers of
antibiotics, such as China and USA, but can still pose a
serious threat if not monitored and regulated strictly. Another
important route through which antibiotic-resistant microbes
can be acquired is through water, where bacterial cell
populations tend to form a „biofilm‟ on the surface of the
water. A report published in Lancet in 2011, showed drinking-
water and seepage samples collected in Delhi to be
contaminated with bacteria containing antibiotic-resistant
gene (NDM-1), which underscored the need for ensuring
clean water supplies and sewage systems. Pharmaceutical
manufacturing facilities, use of human or animal waste as
fertiliser, pollution of river and coastal sea water pose as
additional „water‟ routes for human exposure to antibiotic-
resistant bacterial populations. But in today‟s fast changing
world, there can be many additional routes- increase in
global travel, trade in wildlife and industrialisation of food
today has also greatly contributed to the spread of AMR
across the globe in both poor and developed countries alike.
Ever since the first class of antibiotics were discovered in the
1940s, in addition to treating common contagions, these life-
saving drugs have been used extensively in the clinic post-
operation to prevent various infections. The last new class of
antibiotic was discovered in the 1980s- there has been a long
gap since then in antibiotic development and the efforts
have not been able to keep pace with the growing list of
resistant strains. For instance, vast majority of strains have
become resistant to the commonly used class of antibiotics
“carbapenems”, also known as doctor‟s last line of defence
for many severe infections. This class is among many others
with declining efficacy that urgently need to be replaced by
new and more effective drugs. However, the current
deliberations in the AMR field suggest, that merely inventing
new drugs will not be sufficient and a more nuanced
approach will have to be adopted in tackling the emerging
trends of this epidemic. Decreasing cost and time of gene-
sequencing technologies has greatly helped in not only
detecting but in increasing our molecular understanding of
the resistant strains. These molecular tools can be employed
in investigating new areas of microbial research and for
developing novel methodologies for drug discovery. There
are also many less explored research areas in AMR, for
example, the role of microbial „biofilm‟ and the gut
microbiome in AMR have largely remained unclear. In
addition to this, the emergence of the resistant gram-
negative bacterial strains such as, Acinetobacter baumannii,
Klebsiella pneumonia, Pseudomonas aeruginosa,
Enterobacter cloacae and E. coli, which are responsible for
life-threatening pneumonias and urinary tract infections
among others, also require immediate attention of the
researchers and the policymakers alike. The inability of
majority of the antibiotics to enter the cell of these strains
and the efficient removal of antibiotics by these cells has
made them one of the most imminent infectious disease
threats that would require innovative approaches for
treatment.
The recent Ebola outbreak taught us many lessons -the
central one being the age-old idiom, it's better to be
prepared for an opportunity and not have one, than to have
an opportunity and not be prepared. The opportunity being
the outbreak, in this case. It was evident that an epidemic as
severe as that caused by the Ebola virus can have an
enormous socio-economic impact in less developed
countries and can consequently set them back decades
with respect to development. Therefore, it is important to
reinforce our public healthcare systems with efficient disease
14.
FEATURE ARTICLE
EMERGENCE OF A NEW RESISTANCE
surveillance, health data management systems, health
laboratories and also develop training programmes for
healthcare personnel to manage such outbreaks. It is also
imperative for the government to foster and fund drug
discovery projects in sync with emerging patterns of infectious
diseases, speed up „ethical‟ clinical trials and provide
affordable drugs for endemic infections by partnering with
Pharmaceutical companies. These public-private sector
partnerships can also serve to be useful breeding grounds for
inventing and commercializing cheap rapid point-of-care
medical devices and diagnostics which can be valuable in
handling these outbreaks. However, the most obvious first step
for the prevention of AMR in India would be to devise policies
for regulating drug sales in combination with encouraging
responsible clinical practice and improve sanitation and
hygiene conditions. Lastly, perhaps the most important
intervention would be to devise and implement community
engagement programmes to improve public understanding of
this looming epidemic and about infectious diseases in general
and steps one should take to prevent future outbreaks. To
conceive and execute such interventions, a cross-disciplinary
methodology will have to be undertaken. which would require
participation from all stakeholders.
The „World Antibiotics Awareness week‟ (16-22 November
2015) that kick starts today will not only make people aware of
drug resistant infections but also serve as a reminder that good
health practice is a collective responsibility of the government,
health care providers, medical practitioners and of the people
and that it is important they join hands for a healthy future.
References: 1. New Scientist https://www.newscientist.com/article/dn28180globalstudyrevealssoaringantibioticresistanceinindia/ 2. Nonmedical Uses of Antibiotics: Time to Restrict Their Use? Richard William Meek, Hrushi Vyas, Laura Jane Violet Piddock. PLOS Biology 3. India moves to tackle antibiotic resistance. Nature 2012 4. WHO Report 2014. Antimicrobial Drug Resistance 5. Centre for Disease Dynamics, Economics and Policy
Click on the image to see the emerging data on Antibiotic Resistance from around the world
What is your background?
I am a Probashi Bangali, having spent all my childhood days in
Hyderabad. I grew up in a DRDO township, surrounded by many
Bengali families and celebrating Durga Puja with a gusto. My
childhood was full of running around the neighborhood and
climbing trees, a decisive sense of freedom. My father worked with
the Defence Metallurgical Research Laboratory as a powder
metallurgist, developing new material for the missiles; while mother
spent a lot of time with children from other parents as a Nursery
school teacher. The atmosphere at home was a fine balance of
research induced chaos and education induced discipline,
enhanced by the playfulness of my sister. I sailed through school as
a top ranker till Bachelor's when life dealt me her lessons. I have a
Bachelor's in technology in Industrial biotechnology from Anna
University, Chennai. I scraped up enough grades to get
recommendations letters towards my PhD application to Universities
in the US. Not having learnt the lessons of life during my time in
Chennai, I marched on towards bigger goals and ended up in the
PhD program at the Biochemistry Department of Montana State
University, USA. I rate the agonies of my graduate studies as the
very best of my adult life till date and hoard each memory close. I
moved to Florida for my first post-doc and then to Karolinska
Institute for my second post-doc. I had the divine luck of having
excellent contemporaries as my colleagues and students. But
home is where the heart (could be stomach for all I care) is and it
was only so long I could stay away from the Durga puja and the
Hyderabadi biriyani. I headed home with my hold-all in September
2013 and these days I spend a lot of creative time negotiating the
city traffic.
How has your India Alliance journey been so far?
I will call it a mixed bag. The team makes everyday fun, the
applicants make every day exciting, the Fellows make the work an
excellent learning experience and the Selection Committee
members give us a feeling of being in touch with the who's who of
bio-medical research. There are days I still wonder what made me
leave research, especially when I read exciting articles in structural
biology. Then something at work reminds me how close I really am
to the ground zero of research happening in India and suddenly it
all makes sense. The most stark thing I have learnt on the job is
that I actually enjoy the element of hospitality management of
this job.
When not busy on the job, what do you enjoy doing?
When not at my job (I wont say I am busy, just at work), I have a
full life. I moved back home when I took up this job to spend time
with my parents who have now retired and my grand black
Labrador retriever. As a family, we have a ton of fun filled
evenings and weekends, with a lot of debates thrown in. I
appreciate my parents' support in making 'my' time possible in my
life, as it constitutes a big chunk. I am a curious person who loves
to learn and my primary hobby is to learn. Combined with my
(mostly) boundless energy, this has led me to pursue several
hobbies over the course of my life. I am a trained martial artist (in
Aikido) and a classical dancer (Bharatnatyam and Kathak). These
arts together help my left and right brain to stay in harmony.
When not being artsy, I am a bi-athlete, either running or
swimming. Also, I am always up for a game of badminton. When
all my energy is spent, I love listening to jugaldandis of strings and
percussion. Ustaad Allah Rakha Khan and Pandit Ravi Shakar's
jugalbandis are my all time, anytime, every time favorite. I also
read voraciously, but my reading is not limited to any genre of
books. My favorite thing to read is the newspaper every morning,
specifically the business section, and the news feed on my
Facebook from
WIRED(http://www.wired.com/category/magazine/)
Who inspires you (living or dead)?
Apart from family members (who are all over achievers),I have a
bunch of lady friends in my life, each of who has fought great
personal battle to be where she is now. That these awesome
women would choose me to be part of their lives, part of the
celebration post all the struggles, inspires me. On a lighter note,
Milind Soman inspires me to attempt the Iron(wo)man by my 50th
birthday
INDIA ALLIANCE STAFF CORNER
DR RANJANA SARMA
Grants Adviser
Dr Ranjana Sarma joined the organisation in September 2013
as a Grants Adviser. Apart from infusing great energy in the
office and narrating numerous amusing stories, Ranjana has
been involved with many activities at IA, from grants work to
SciComm workshops, website and is currently the secretary of
the Research Training Fellowship scheme. In this interview she
reminisces about her childhood and research days, recounts
how India Alliance experience has been a mixed bag, her
love for martial arts and dance, and much more..
16.
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IMAGES IN THIS ISSUE
Image by Dr Thomas Pucadyil, Intermediate Fellow, IISER Pune Montage of a single membrane tube of ~40 nm in diameter
seen under the fluorescence microscope undergoing multiple
cuts in response to dynamin and GTP addition
Image by Dr Sheetal Gandotra, Intermediate Fellow, IGIB,
New Delhi
Mycobacterium tuberculosis infected fibroblast imaged
using a Zeiss Scanning Electron Microscope. The image
reveals the aggressive intracellular growth of the
bacterium followed by necrosis.
16.