News & Views Issue 6, November 2015
INDIA ALLIANCE
EDITORIAL
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
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
TH 6
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.
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).
3.
INDIA ALLIANCE
OUTREACH EVENTS 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 Balasubramanianâ€&#x;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, Kingâ€&#x;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.
4.
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
Iqbal encouraged the participants to deliberate on the topic of
Daspalla Hotel in Hyderabad from 14-15 September 2015 which
Public Engagement with Science and in what ways, as scientists
was attended by 34 PhD students, Postdocs, junior Faculty and
and clinicians, they could take their research to the public and
Clinicians from 29 different institutions across India such as, IISER
collaborate with them to get fresher research perspectives. She
Trivandrum, Central Food Technological Research Institute,
also initiated an interesting discussion on what ails productive
Mysore, Centre for DNA Fingerprinting and Diagnostics,
communication between the clinicians and basic research
Hyderabad, Indian Institute of Science, Education and
community in India. Grants Adviser, Dr Madhankumar
Research, Kolkata, DAPM RV Dental College and Hospital, IIT
Anandhakrishnan concluded the first day by giving a brief
Bombay, Christian Medical College, Vellore, Shiv Nadar
overview of the India Alliance Fellowship schemes and
University, Greater Noida, Mysore Medical College and
application process. The participants discussed various issues
Research Institute, Mysore, CSIR- Centre for Cellular and
concerning the workshop, career choices and their current
Molecular Biology, Hyderabad, National Centre for Cell Science
research with the India Alliance staff and the workshop mentors
(NCCS), Pune, National Institute of Mental Health and
over the Networking dinner.
Neurosciences, Bangalore, Indian Institute of Advanced Research, Gandhinagar, BITS-Pilani, Hyderabad Campus,
The second day of the workshop covered topics such as,
ACTREC, Mumbai, Indian Institute of Science Bangalore, Indian
Ethics in Research, Clinical research, Grant and Manuscript
Institute of Chemical Technology Hyderabad, , Institute of
writing, talks on which were given by Dr Anant Bhan (Yenepoya
Bioinformatics and Applied Biotechnology (IBAB), Bangalore,
University, Mangalore), Dr Anurag Agrawal (IGIB, New Delhi), Dr
CSIR-Centre for Cellular and Molecular Biology, Hyderabad,
Lolitika Mandal (IISER Mohali), Dr Mahak Sharma (IISER Mohali)
Amity University, New Delhi, Institute Of Medical Sciences,
and Prof Sandhya Visweswariah (IISc Bangalore). The Mentors
Banaras Hindu University, All India Institute of Medical Sciences,
stimulated various discussions on these topics and ensured the
New Delhi, Acharya Nagarjuna University, Guntur, University of
participants were not wary of asking important questions about
Mysore, Defence Institute of Physiology and Allied Sciences
research career development, setting up a lab, postdoc
(DIPAS), DRDO, New Delhi, CSIR-Central Drug Research Institute,
opportunities, clinical research and many more. The highlight of
School of Life Sciences, Manipal and Pondicherry University.
the workshop for the participants was the research proposal discussion, where participants received useful feedback and
The first day of the workshop focused on oral presentation
advice on the structure and content of their proposals from the
skills and important elements of an effective professional
mentors.
presentation. This session was conducted by Mrs Sumathy Haridas, an HR consultant from Bangalore, who gave useful
The enthusiasm and active questioning at the workshop by
advice on how to prepare the message of a presentation,
the participants reinforced the importance of Science
appear confident, speak articulately and engage the
Communication in nurturing and training the future researchers
audience. Her session consisted of various hands-on exercises
of India.
for the participants that ensured active participation. Following
Watch this space for the announcement of the next two-day SciComm workshop and other communication training initiatives
this session, India Alliance Public Engagement officer, Dr Sarah
5.
INDIA ALLIANCE
SCIENCE COMMUNICATION WORKSHOPS From a SciComm participant to an IA Fellow 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. Dr Yogesh Dahiya, Early Career Fellow, IISER Mohali
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 Giridhara R Babu, Intermediate Fellow, Public Health Foundation of India
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 Tavpritesh Sethi, Early Career Fellow, AIIMS, New Delhi
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.
One-day SciComm101 workshop at Vinayaka Missions University Salem, Tamil Nadu India Allianceâ€&#x;s SciComm101 workshop team reached the
Tiruchengode, Sivaraj Siddha Medical College.
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
In addition to the life sciences streams, the workshop
Engineering, Namakkal, Padmavani Arts and Science College
participants came from varied backgrounds, such as nursing,
for Women, Salem, Periyar University, Salem, Kerala Agricultural
biomedical and electrical engineering, architecture, dental
University, Thrissur, Kerala, Tamil Nadu Agricultural University,
science, chemistry and physics. The attendees particularly
Mahendra Arts and Science College, Salem, Sri Vijay Vidyalaya
appreciated the interactive nature of the sessions and for the
College of Arts and Science, J.K.K Nattraja College of
opportunity of receiving this unique training which is not
Pharmacy, Government Mohan Kumaramangalam Medical
available to most of them in their respective institutions.
College, Salem, Vivekananda College of Arts and Science,
6.
INDIA ALLIANCE
PUBLIC ENGAGEMENT CORNER
As part of a public engagement exercise, the India Alliance launched its first „Research Image Competitionâ€&#x; 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.
W E C A R E , F O R E Y E C A R E , E V E R Y W H E RE B y D R S R I NI VA S M A R M A M UL A , R e s e a r c h T r a i ni ng F e l l o w
THE CANCER B y D R S A N JA Y C H I L BUL E , R e s e a r c h T r a i ni ng F e l l ow
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.
Newly formed cancer cells of bone cancer are spreading out centrifugally from their parent cells which probably may be happening inside the body.
INTRICATE ARRANGEMENT OF DIVERSE CELL TYPES IN THE GUT OF A FRUIT FLY B y D R B US H R A A T E E Q , I n t e rm e di a t e F e l l o w & D R A N JA L I B A J PA I , E a r l y C a r e e r Fellow Other Image Creators: Ms Umanshi Rautela, Prof Pradip Sinha
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
7.
INDIA ALLIANCE FELLOW SPOTLIGHT
DR SHEETAL GANDOTRA Intermediate Fellow, IGIB, New Delhi
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..
What are you working on and what impact do you hope it will have?
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-
Tuberculosis disease pathology has had a long standing link with lipids- be it the virulence imparting lipids of the bacterium
economic problems that deeply affect the growth of India. While we
Mycobacterium tuberculosis or the host lipids that accumulate in
hope that the basic research we carry out in our lab is able to offer
the granuloma. We are working on identifying mechanism(s)
new sustainable solutions to tuberculosis treatment, we do realize that
whereby the intracellular bacilli alter the host cellâ€&#x;s lipid storage
by inspiring more people in our neighbourhood, in our city, and in the
depots -the lipid droplets, such that the characteristic lipid loaded
country, towards logic, reasoning, and high quality research, the
foamy macrophages develop and at the same time the bacilli
scientific community holds great responsibility in bringing about this
make use of fatty acids from the host cell. By addressing the first
positive change.
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
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
learning every day on how to really become a scientist because that is so much more than simply “doing science�. There is so
PhD I started learning Bharatanatyam; I would travel 3 hours from
much to learn in terms of managing a lab and a team and I think
Manhattan to Queens for a 1 hour class. In the UK, I became an avid
I grow a little bit with every student that joins my group or
gym fan, and since moving back to India, I think it is the support of
engages me in their questions. In a way, their questions inspire me
family that keeps me going. I like to paint and experiment with my
further. Last but not the least, the pathogen I work on-
creative abilities- be it a wall or a window pane at home. While I get
Mycobacterium tuberculosis continues to challenge me and that
little time to do such things, the build up to a creative pursuit is equally
really is the basis of what I work on.
important to me.
8.
INDIA ALLIANCE
RESEARCH HIGHLIGHTS
Novel anti-cancer compound targeting DNA cutting enzyme, Topoisomerase I DR BENU BRATA DAS, Intermediate Fellow, Indian Association for the Cultivation of Science, Kolkata DNA Topoisomerase 1 (Top1) is an essential enzyme for
exhibited potent inhibition of Top1 through stabilization of
expediting the release of torsional stress generated during
Top1cc as shown by its anti-cancer activity against human
various DNA transactions. Top1 is expressed much higher in
cervical carcinoma (HeLa) and breast carcinoma (MCF-7)
various tumour cells than the normal cells, therefore,
cells. These results suggest that the selected thiohydantoin
modulating the Top1 levels could be an important therapeutic
may be a suitable lead to develop as potential anti-cancer
treatment for cancer. Top1 when trapped on the DNA as
compound.
Top1-DNA covalent complexes (Top1cc) by anticancer drug 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. 102:54051.
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
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.
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
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
each other. Yet, how the two PAPs select their respective
messenger RNA (m RNA) synthesis in the nucleus to translation
target mRNAs is not understood. Using Star-PAP as an
in the cytoplasm. 3‟-end RNA processing is an essential step in
example, we established the mechanism of PAP specificity
mRNA synthesis that involves addition of a polyadenosine (A)
where Star-PAP recognizes a distinct sequence element at the
tail at the 3‟- untranslated region (UTR) by enzyme called
trailing 3‟–UTR and excludes PAPα from the UTR. There are two
poly(A) polymerase (PAP). Poly(A) tail is essential for stability
aspects of PAP specificity – recognition of target mRNA and
and efficient translation of the mRNA. There are two major
exclusion of the other PAP, rendering the mRNA to exclusive
poly(A) polymerases involved in general polyadenylation in
control of one PAP. We identified Star-PAP recognition motif
the nucleus - canonical PAPα and Star-PAP. The two PAPs
(AUA) on the mRNA target upstream of poly(A) site.
have distinct niche of target mRNAs and are independent of
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
Unique Nerve Activity in the Cerebellum DR VATSALA THIRUMALAI, Intermediate Fellow, NCBS, Bangalore
Ever wonder how you keep your balance? This is
while a negative voltage is dubbed the „down‟ state. Neurons
something that we learn to do as toddlers, and it involves the
in the „up‟ state produced tonic pulses, while neurons in the
coordinated effort of various muscles in the body. An area at
„down‟ state produced short bursts of activity with the help of
the base of the brain called the cerebellum controls this effort,
an ion channel called AMPAR.
and synchronizes our muscles by sending messages in the form
Cells called motor neurons in the spinal cord carry the final
of electrical signals along cells called Purkinje neurons. These
command from the nervous system to the muscles. We
signals consist of steady „tonic‟ activity or short „bursts‟ of
recorded the activity of motor neurons and Purkinje neurons
activity. Previous studies in unconscious mammals suggest that
at the same time. This revealed that Purkinje neurons receive
these neurons can spontaneously switch between the two
a copy of the motor command that goes to the muscle and
types of electrical signals.
produce short bursts of electrical activity in response. This
However, it is not clear whether this switch occurs in awake
effect required AMPAR activity, and was blocked by
animals, or how these nerve activities control muscle
molecules that inhibit AMPAR. Furthermore, the timing of these
movements. It is technically challenging to record the voltage
short bursts with respect to the motor command changes from
of single Purkinje neurons of conscious rodents, so this problem
one Purkinje neuron to another. Future work will investigate
was avoided by using zebrafish larvae instead. These larvae
how the Purkinje neurons receive and process the information
are small, transparent and lack a skull, which makes it possible
in the motor command.
to record the activity of the cerebellum using tiny glass AMPA receptor mediated synaptic excitation drives statedependent bursting in Purkinje neurons of zebrafish larvae Mohini Sengupta, Vatsala Thirumalai. eLife
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
Image above: Pseudocolor images of Purkinje neurons in adult zebrafish cerebellum. Image created by Lena Robra and Mohini Sengupta
the two. The switch is controlled in part by the voltage on the neurons' surface. A positive voltage is called the „up‟ state,
10.
A high throughput platform to study cell membrane fission DR THOMAS PUCADYIL, Intermediate Fellow, IISER Pune
Cell membrane fission requires the localized application of
supported membrane tubes or SMrTs. Membrane tubes
curvature stresses to the lipid bilayer in order for a membrane
represent an ideal mimic of the necks of clathrin-coated pits,
tube to go from a highly constricted to a cut state. Since
the physiological substrate upon which dynamin is thought to
these topological transformations require the bilayer to
act in cells. Since the tubes are stably laid out on a glass
deviate from its preferred planar configuration, membrane
surface, one can now use conventional wide field
fission is an energetically unfavorable process. The GTPase
microscopic approaches to locally probe changes in
dynamin represent a group of specialized protein machines
membrane shape during a single dynamin-catalyzed fission
that catalyze membrane fission. Dynamin manages this
event. Indeed, results from such experiments reveal the
process by self-assembling into a helical scaffold that
necessity for GTP hydrolysis during dynamin-catalyzed
hydrolyzes GTP to constrict and cut the underlying membrane
membrane fission. Dynamin self-assembly into a helical
tube. How it does it has been a subject of intense controversy.
scaffold constricts the underlying tube but does so to a
Membrane fission reactions are carried out in a confined
moderate extent. GTP hydrolysis is required for further
region of the membrane enclosed within a 10 nm wide, 2-rung
constricting the underlying tube for it to reach dimensions
scaffold comprised of ~26 molecules of dynamin. Thus, the
necessary for fission.
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
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.
Structural insights into the channels of the mitochondria DR R MAHALAKSHMI, Intermediate Fellow, IISER Bhopal Voltage-dependent anion channels, or VDACs, are pore-
interdependent contribution of the N-helix and cysteine
forming outer mitochondrial membrane proteins that help
residues to the function, barrel folding and stability of hVDAC-
govern cellular homeostasis. These are 19-stranded
2. Our work is an important advancement in understanding
transmembrane β-barrel proteins (as shown in the image
hVDAC-2 barrel dynamics and provides insight into factors
above) that shuttle various products of the metabolic process
that functionally demarcate this protein from the other
between the cytoplasm and mitochondria in a cell. Of the
VDACs. Our work will help us understand the important role
three isoforms (-1, -2 and -3) of VDACs in humans, hVDAC-2 is
played by the hVDAC-2 protein in deciding the fate of the
more important for cell survival. Current understanding of the
cell. We also demonstrate the evolutionary relevance of the
structure-function relationship of anti-apoptotic hVDAC-2 is still
N-terminal 11-residues of hVDAC-2 in the context of cysteine
at its inception. It has a unique 11-residue stretch at the N-
conservation.
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
N-helix and cysteines inter-regulate human mitochondrial VDAC-2 function and biochemistry. Svetlana Rajkumar Maurya and Radhakrishnan Mahalakshmi. The Journal of Biological Chemistry
11.
FEATURE ARTICLE
EMERGENCE OF A NEW RESISTANCE DR SARAH IQBAL, PUBLIC ENGAGEMENT OFFICER, INDIA ALLIANCE
Wellcome Library, London
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,
microbes but the remaining population could become
applauding the discoveries concerning novel therapies
resistant to this medication and keep growing. Additionally,
against infections, is in grim contrast to global health
there is a collateral consequence of using an antimicrobial-
epidemic of antimicrobial resistance (AMR) that the world is
the drug not only removes the infectious microbes but also
facing today. AMR has fast become an obstacle in the
some of the healthy ones, which leads to the infectious and
prevention and treatment of variety of infections caused by
resistant microbes to take over the body. This is the reason
bugs such as bacteria, parasites, viruses and fungi, which
why the doctor strictly instructs us to finish the course of the
cause HIV, influenza, malaria, tuberculosis and host of other
prescribed antibiotic even if we feel better after the first few
infections. Not paying heed to the „words of caution‟ of the
doses. It has also been observed that low-level of exposure to
inventor of the first legitimate antibiotic has led us towards a
certain antibiotics leads to increased incidence of mutations,
major public health crisis world-wide, which could become
non-reproductive gene transfer between bacteria and
more severe in the less developed regions, where infections
consequently a higher likelihood of the bacterial populations
are rampant and healthcare services abysmal.
to acquire resistance.
AMR can be loosely defined as resistance of the infectious
Let us now zoom into one of the biggest centres of this
bugs against the medications used to eliminate them, by
epidemic with highest users of antibiotics and explore social,
overpowering its toxic effects. A bug or a microbe acquires
environmental and medical factors which are giving rise to
resistance through modifications in its genes- an important
AMR. Even though the global report by WHO on AMR in 2014
illustration of Darwin‟s natural selection. For instance,
indicates that AMR crisis is present in every region of the
antibiotics work through inactivating proteins in the bacteria
world, its health and economic consequences in a middle
thereby shutting down its growth machinery. Any genetic
income country such as India could be very damaging and
change in the protein can prevent the antibiotic to do its
long-lasting. In nearly every corner of India where one has
work effectively. Alternatively, the genetic modification could
access to medicines, antibiotics are given to young children
lead to an increased production of the antibiotic‟s target
and adults alike, in an unsupervised and reckless manner.
protein, which makes the drug ineffective in inactivating all of
Easy over-the-counter availability, irresponsible clinical
that protein. Adding to the existing molecular complexities,
conduct and strong insistence by patients for antibiotics for
the bacterial evolutionary survival mechanisms enable these
even minor infections, are some of the major factors leading
microorganisms to literally borrow genes from one another.
to high use of this medication in India. For a lot of Indians,
This further leads to the spread of resistant genes in the
staying home to recover from infections can cost a job and
bacterial population.
taking the wrong drug (for e.g, an antibiotic for a viral infection) can prolong sickness. According to a report by
Let us zoom out of the bacterial cell and describe the
Center for Disease Dynamics, Economics and Policy, that
possible causes that can lead to AMR. If a recommended
surveyed antibiotic use and AMR incidence in 69 countries
drug is not used for the time necessary for eliminating the
including India, suggests that globally 80% of antibiotics are
infection, it kills a small population of infection-causing
used outside the hospital where there is very little supervision.
12.
FEATURE ARTICLE
EMERGENCE OF A NEW RESISTANCE
India was the highest consumer of antibiotics according to a
Ever since the first class of antibiotics were discovered in the
survey done in 2010, using up to 13 billion Standard Unit (SU)
1940s, in addition to treating common contagions, these life-
of antibiotics compared to 7 billion in USA. This unregulated
saving drugs have been used extensively in the clinic post-
sale and over-prescription of antibiotics is one of the primary
operation to prevent various infections. The last new class of
causes of AMR cases in India. Poor sanitation and
antibiotic was discovered in the 1980s- there has been a long
widespread malnutrition in the country only augments the
gap since then in antibiotic development and the efforts
AMR-related disease burden. Resistance developed due to
have not been able to keep pace with the growing list of
nonmedical consumption mainly results from its use as
resistant strains. For instance, vast majority of strains have
veterinary medicine, growth-promoters in livestock and in
become resistant to the commonly used class of antibiotics
agriculture. This type of use, however, is not as high in India in
“carbapenems”, also known as doctor‟s last line of defence
comparison to other countries that are heavy-consumers of
for many severe infections. This class is among many others
antibiotics, such as China and USA, but can still pose a
with declining efficacy that urgently need to be replaced by
serious threat if not monitored and regulated strictly. Another
new and more effective drugs. However, the current
important route through which antibiotic-resistant microbes
deliberations in the AMR field suggest, that merely inventing
can be acquired is through water, where bacterial cell
new drugs will not be sufficient and a more nuanced
populations tend to form a „biofilm‟ on the surface of the
approach will have to be adopted in tackling the emerging
water. A report published in Lancet in 2011, showed drinking-
trends of this epidemic. Decreasing cost and time of gene-
water and seepage samples collected in Delhi to be
sequencing technologies has greatly helped in not only
contaminated with bacteria containing antibiotic-resistant
detecting but in increasing our molecular understanding of
gene (NDM-1), which underscored the need for ensuring
the resistant strains. These molecular tools can be employed
clean water supplies and sewage systems. Pharmaceutical
in investigating new areas of microbial research and for
manufacturing facilities, use of human or animal waste as
developing novel methodologies for drug discovery. There
fertiliser, pollution of river and coastal sea water pose as
are also many less explored research areas in AMR, for
additional „water‟ routes for human exposure to antibiotic-
example, the role of microbial „biofilm‟ and the gut
resistant bacterial populations. But in today‟s fast changing
microbiome in AMR have largely remained unclear. In
world, there can be many additional routes- increase in
addition to this, the emergence of the resistant gram-
global travel, trade in wildlife and industrialisation of food
negative bacterial strains such as, Acinetobacter baumannii,
today has also greatly contributed to the spread of AMR
Klebsiella pneumonia, Pseudomonas aeruginosa,
across the globe in both poor and developed countries alike.
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
13.
FEATURE ARTICLE
EMERGENCE OF A NEW RESISTANCE
surveillance, health data management systems, health
hygiene conditions. Lastly, perhaps the most important
laboratories and also develop training programmes for
intervention would be to devise and implement community
healthcare personnel to manage such outbreaks. It is also
engagement programmes to improve public understanding of
imperative for the government to foster and fund drug
this looming epidemic and about infectious diseases in general
discovery projects in sync with emerging patterns of infectious
and steps one should take to prevent future outbreaks. To
diseases, speed up „ethical‟ clinical trials and provide
conceive and execute such interventions, a cross-disciplinary
affordable drugs for endemic infections by partnering with
methodology will have to be undertaken. which would require
Pharmaceutical companies. These public-private sector
participation from all stakeholders.
partnerships can also serve to be useful breeding grounds for inventing and commercializing cheap rapid point-of-care
The „World Antibiotics Awareness week‟ (16-22 November
medical devices and diagnostics which can be valuable in
2015) that kick starts today will not only make people aware of
handling these outbreaks. However, the most obvious first step
drug resistant infections but also serve as a reminder that good
for the prevention of AMR in India would be to devise policies
health practice is a collective responsibility of the government,
for regulating drug sales in combination with encouraging
health care providers, medical practitioners and of the people
responsible clinical practice and improve sanitation and
and that it is important they join hands for a healthy future.
Click on the image to see the emerging data on Antibiotic Resistance from around the world
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
14.
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..
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
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/)
city traffic.
Who inspires you (living or dead)? How has your India Alliance journey been so far?
Apart from family members (who are all over achievers),I have a
I will call it a mixed bag. The team makes everyday fun, the
bunch of lady friends in my life, each of who has fought great
applicants make every day exciting, the Fellows make the work an
personal battle to be where she is now. That these awesome
excellent learning experience and the Selection Committee
women would choose me to be part of their lives, part of the
members give us a feeling of being in touch with the who's who of
celebration post all the struggles, inspires me. On a lighter note,
bio-medical research. There are days I still wonder what made me
Milind Soman inspires me to attempt the Iron(wo)man by my 50th
leave research, especially when I read exciting articles in structural
birthday
biology. Then something at work reminds me how close I really am
16.
IMAGES IN THIS ISSUE
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.
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
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