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GS-‐2012 - National Centre for Biological Sciences

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<strong>GS</strong>-­‐2012 <br />

Handbook <strong>for</strong> Interviews <br />

Photo courtesy, Durafshan Sakeena, PhD Scholar <br />

Na9onal <strong>Centre</strong> <strong>for</strong> <strong>Biological</strong> <strong>Sciences</strong>, TIFR, Bangalore <br />

May-­‐June 2012


May 2012 <br />

Dear Students, <br />

I write on behalf of the community at NCBS to extend a warm welcome to you. The call-­leLer,<br />

sent separately, invi9ng you to par9cipate in the interviews carries details on the <br />

dates, reimbursements and travel to NCBS. This handbook is provided in an aLempt to help <br />

you in your experience with the selec9on process. There are sec9ons which should <br />

familiarize you with the actual interview process as well as those more helpful to students <br />

eventually joining the program. We also include a sec9on where the Faculty at NCBS <br />

provides an overview of their research programs. We encourage you all to read this sec9on <br />

be<strong>for</strong>e your visit and meet with members of the laboratories that you find par9cularly <br />

interes9ng. Addi9onal in<strong>for</strong>ma9on on all laboratories and the programs on offer are <br />

available on the NCBS website. <br />

We hope that the NCBS experience will be enriching <strong>for</strong> you and look <strong>for</strong>ward to <br />

seeing you in May. <br />

With best wishes <br />

Head Academics <br />

national centre <strong>for</strong> biological sciences<br />

tata institute of fundamental research


1. PhD & Int-­‐PhD programs <br />

GRADUATE STUDIES AT NCBS <br />

NCBS offers a graduate program leading to the award of a PhD degree to students who hold a Masters <br />

degree in a Basic Science or a Bachelors degree in an Applied Science such as Medicine, Engineering <br />

etc. The Integrated PhD program seeks students with an excellent academic record at the B.Sc. <br />

level, strongly mo9vated to pursue a career in research. <br />

The Integrated Biology (iBio) and Theore9cal Studies programs at NCBS provide a s9mula9ng <br />

environment <strong>for</strong> students with backgrounds in physics, chemistry and mathema9cs to apply their <br />

knowledge to understanding concepts in biology. Students who are interested in iBio research <br />

projects must first be accepted into the PhD or integrated-­‐PhD program at NCBS through the <br />

standard applica9on procedure. <br />

In all a<strong>for</strong>emen9oned programs, students register <strong>for</strong> a PhD at the TIFR Deemed University typically <br />

1.5-­‐2 years from the date of joining, a[er mee9ng course requirements and qualifying a <br />

comprehensive examina9on. <br />

M. Sc by Research: A very small number of students featuring on the wait list of the Integrated PhD <br />

selec9on interview may be appointed to this program with salary support on PI grants. <br />

The MSc in Wildlife & Conserva9on program is offered only at NCBS and selec9ons are made based on a <br />

separate test and interview process. The next selec9ons <strong>for</strong> this program will be in 2014


2. Selec9on Process <br />

<strong>GS</strong>-­‐2012 Interviews <br />

Candidates are invited to apply in response to adver9sements appearing in na9onal <br />

newspapers and magazines in August/September every year. Candidates short-­‐listed on <br />

the basis of their per<strong>for</strong>mance in a wriLen test, academic record and leLers of evalua9on <br />

are interviewed <strong>for</strong> admission. NCBS sends out an applica9on package to students who <br />

qualify the TIFR entrance test <strong>for</strong> Biology, Physics or Chemistry. Per<strong>for</strong>mance in the wriLen <br />

test, together with the in<strong>for</strong>ma9on requested in the applica9on package is used to short-­list<br />

candidates <strong>for</strong> interviews at Bangalore in May 2012. <br />

Interviews <strong>for</strong> the PhD/Int-­‐PhD programs at NCBS typically comprise two rounds. There is some <br />

overlap in the list of candidates invited to interview at DBS or NCBS and it is possible that <br />

some candidates are offered admission in both centres. Candidates are however expected <br />

to accept the offer at only one centre.


<strong>GS</strong>-­‐2012 Interviews <br />

3. Interviews <br />

In the first round, interview panels will typically comprise 3 members of the faculty at NCBS. Some <br />

commiLees include a minimum of one or two specialists in the areas of Physics or Chemistry. In <br />

this round all candidates should expect to be ques9oned on their basic understanding of <br />

Biology, Chemistry or Physics as well as quan9ta9ve and reasoning skills. The commiLee will <br />

probe your understanding of concepts taught in high school and at the undergraduate level. <br />

Please do not prepare <strong>for</strong> the interviews by memorizing material! All students are interviewed <br />

in this round, which is typically completed in one day and may some9mes extend into the <br />

morning of the second day. Based on per<strong>for</strong>mance in the first round, students are short-­‐listed <br />

<strong>for</strong> the second round of the interview process. This list of candidates short-­‐listed <strong>for</strong> the second <br />

round will be posted by 12 noon on the second day or earlier. Lists are drawn up only a[er all <br />

first round interviews are completed. <br />

In the second round, interview panels comprise 4 members and again some commiLees will have <br />

greater representa9on of faculty with core exper9se in areas of Chemistry or Physics. This <br />

interview may typically extend from 30-­‐45 minutes and tests <strong>for</strong> more in-­‐depth understanding <br />

and the ability to apply the knowledge of an area of special interest to the candidate. Typically <br />

the statement of purpose in the applica9on package is used as a basis of ques9oning. However, <br />

candidates have to be prepared <strong>for</strong> ques9ons that have been taught at a more advanced level <br />

in special papers or via projects etc. In previous years, ques9ons have also been based on <br />

original research ar9cles that were distributed to all candidates prior to the interviews. <br />

Candidates uncom<strong>for</strong>table or unable to handle ques:ons in a par:cular area must indicate this <br />

to the commi


The final list of selected candidates, drawn up in consulta9on with Chairpersons of the <br />

commiLees and based on the per<strong>for</strong>mance in both rounds of interviews, will be announced <br />

late a[ernoon/ evening of the fourth day. <br />

<strong>GS</strong>-­‐2012 Interviews <br />

Waitlisted candidates: Students on the wait-­‐list if supported by external funding from the <br />

CSIR, ICMR or DBT can join the PhD program if sponsored by a laboratory at NCBS. <br />

Alterna9vely, a student on the wait-­‐list may also join the graduate program with salary support <br />

from the Principal Inves9gator’s [PI] grant. Admission and con9nua9on on the graduate <br />

program in both situa9ons is con9ngent on associa9on with the PIs laboratory. <br />

This op9on is not available to students short-­‐listed on the Integrated PhD program. Faculty at <br />

NCBS will post in<strong>for</strong>ma9on regarding the availability of grants on the days of the PhD <br />

Interviews. <br />

Note: <br />

Please report at NCBS by 8.30AM on the first day of the interviews. There is a short session <br />

on the morning of the first day to orient you to the selecKon process and assign students to <br />

various panels. NCBS student volunteers who guide you through the interviews will be also <br />

be assigned in this session.


<strong>GS</strong>-­‐2012 Overseas Applica9ons <br />

NCBS invites applica9ons from students who enrolled in Colleges and University outside <br />

the Indian Subcon9nent <strong>for</strong> their undergraduate studies. The entrance test is waived <br />

<strong>for</strong> overseas applicants. However students who would like to be considered <strong>for</strong> the <br />

graduate program at NCBS are encouraged to write Head Academic Ac9vi9es be<strong>for</strong>e <br />

November each year. <br />

The academic office will assist you with the submission of an applica9on package and the <br />

subsequent steps in the selec9on process. In some instances we offer the op9on to <br />

interview students via skype/video conference if short-­‐listed <strong>for</strong> the interviews. If <br />

selected to the program students are expected to join on August 1 st or at the earliest <br />

possible date therea[er. <br />

There are specific requirements <strong>for</strong> travel and visa documents <strong>for</strong> <strong>for</strong>eign na9onals which <br />

have to be completed prior to arrival at NCBS. The academic office coordinates with <br />

the establishment office at NCBS to assist students through this process.


In<strong>for</strong>ma9on related to Interviews <br />

4. Accommoda9on and Meals during the Interviews <br />

Candidates are expected to make their own arrangements <strong>for</strong> stay during interviews <br />

as NCBS does not provide accommoda9on. In<strong>for</strong>ma9on regarding short-­‐term <br />

leased accommoda9on and hotels close to our campus availed by students in <br />

previous years is provided in the brochure. NCBS will not act as an intermediary <br />

in these arrangements. <br />

Meals -­‐ Breakfast, Lunch and Tea -­‐ are served to candidates Wed-­‐Fri on Interview <br />

dates. Breakfast and lunch will be served on Saturday. Meals are free. <br />

Accompanying persons may purchase food at the cafeteria and canteen on the <br />

Campus, which operate at set 9mes. If staying on <strong>for</strong> dinner, please in<strong>for</strong>m the <br />

canteen management at lunch 9me as dinner service is limited on campus. <br />

Please do not <strong>for</strong>ward requests <strong>for</strong> Guest House accommodaKon via members of <br />

the Staff – academic, administraKve or technical – at NCBS during the period of <br />

the Interviews.


In<strong>for</strong>ma9on related to Interviews <br />

5. Material you should bring to the Interviews <br />

• Candidates are expected to bring a printed copy of the leLer invi9ng them to the <br />

interview; proof of ID in the <strong>for</strong>m of a University/Ins9tute ID card/ PAN Card may be <br />

required and should be available if needed. <br />

• A copy of your 9cket is required to process reimbursement, which will be given to <br />

you on the second day of the Interviews. <br />

• Air travel is reimbursed to the extent indicated in the leLer from NCBS. The <br />

incoming boarding pass has to be submiLed to process reimbursement. <br />

• Students traveling by bus are required to present Xerox copies of 9ckets or proof of <br />

the inward journey. <br />

• The TA/DA <strong>for</strong>m should be submiLed on the day of arrival. This is applicable only to <br />

candidates living outside Bangalore. <br />

Please carry: <br />

Call leLer; proof of ID; copy of 9cket; TA/DA <strong>for</strong>m which can be downloaded from our website


In<strong>for</strong>ma9on related to Interviews <br />

6. Hotels & Commercial Guest Houses near NCBS-­‐ par9al list <br />

Stayaf<strong>for</strong>d Service Apartment, No. 1629, C Block, Sahakar Nagar, Bangalore 92 <br />

Contact Mr. Santosh 9880194240 <br />

Satya Com<strong>for</strong>ts Service Apartments, B -­‐ 31, Chitrakut Century, Behind North Side Hospital, <br />

Sahakar Nagar, Bangalore Contact Ms. Annapurna -­‐ Tel: 9980101881, Tel: <br />

08042031881/32951881 fax: 080-­‐42031881 Email: satyacom<strong>for</strong>ts@hotmail.com <br />

The Royale Senate, No 24, Bellary Road, Hebbal, Bangalore – 24, Ph: 91 80 23439860, Fax: 91 80 <br />

2343 1759 info@theroyalesenate.com <br />

Chairman's Resort, #14/1, Kodigehalli Main Road, Sahakarnagar, Bangalore -­‐ 560 092 Tel: <br />

+91-­‐80-­‐40703703, 23546162 Contact:+91-­‐9980269978 <br />

Narayana Com<strong>for</strong>ts, No. 9/9, Kendriya Vihar Apts, Bb Rd, Yelahanka, Bangalore 560064, Tel: <br />

080-­‐28462752/51/53, 22792780 Contact: Subhash Chandra Mobile 9886217208 <br />

Shreyas Residency 9/8 N.H 7 B.B Road, Amanikere, Yelahanka, Bangalore. Contact Subhas <br />

9886217208 <br />

Royal Orchid Resort & Conven9on <strong>Centre</strong> (Previously Doddi’s Resort) Allalasandra, Bellary <br />

Road, Yelahanka, Near Jakkur Flying Club, Bangalore 560 065, india Tel +91 80 2856 0668 <br />

Fax +91 80 2856 0671 Email rooms@royalorchidhotels.com <br />

Please note: NCBS will not act as an intermediary in arranging accommoda9on during the interviews


Orienta9on Program <strong>for</strong> new students <br />

7. Acceptance of the offer from NCBS <br />

A <strong>for</strong>mal offer to join the program will reach you within a period of 10-­‐15 days from the date of the <br />

interview. You are expected to in<strong>for</strong>m NCBS about your acceptance of the offer or otherwise by the date <br />

specified in the leLer. <br />

8. Accommoda9on <strong>for</strong> graduate students <br />

NCBS offers accommoda9on to all students selected on the graduate program. Students on the main lists of <br />

the PhD and Int-­‐PhD have priority, followed by PhD students on grants and the M. Sc students. Rooms <br />

are alloLed only a[er students arrive on campus and cannot be reserved. Rooms are alloLed only a[er <br />

the submission of a joining report and comple9ng administra9ve <strong>for</strong>mali9es in August. <br />

9. Orienta9on and Rota9ons <strong>for</strong> incoming graduate students <br />

New students join NCBS on Wednesday August 1 st 2012. All new students must par9cipate in <br />

the Orienta9on Program. During the program, sessions are arranged with faculty members <br />

to discuss work ongoing in their laboratories. The program also includes sessions with <br />

individuals who manage Research, Technical and Administra9ve Services at NCBS. In the <br />

course of the Orienta9on Program, students are guided through procedures such as the <br />

comple9on of the mandatory medical test and administra9ve <strong>for</strong>mali9es towards joining in <br />

the course of this program. Administra9ve staff will assist you in this. Addi9onal <br />

in<strong>for</strong>ma9on on rota9ons, courses etc. will be provided during the Orienta9on Program <br />

Laboratory allotments <strong>for</strong> graduate studies are ONLY made a[er the comple9on of laboratory <br />

rota9ons. No student in the graduate program is exempt from laboratory rota9ons.


Your contact: phd@ncbs.res.in <br />

Academic Office <br />

Academic Office <br />

K.S. Vishalakshi <br />

MaLers related to Student Affairs are managed by the <br />

Academic Office, in coordina9on with the <br />

Administra9ve Office. The academic office is managed <br />

by Ms NN Shantha and Ms KS Vishalakshi. <br />

Ms KS Vishlakshi is the primary contact <strong>for</strong> all <br />

correspondence related to selec9on and joining the <br />

program at NCBS. Do not call unless there is an <br />

emergency. Please do not contact our faculty <strong>for</strong> <br />

in<strong>for</strong>ma9on regarding the interviews. <br />

All queries related to the interviews should be directed <br />

to phd@ncbs.res.in. <br />

In case of medical emergencies or clashes with exams <br />

or other interviews, suitably jus9fied requests <strong>for</strong> <br />

rescheduling within the assigned dura9ons of the <br />

Interviews may be submiLed to phd@ncbs.res.in with <br />

the subject line Name_<strong>GS</strong>2012_date change.


esearch opportuniKes <strong>for</strong> <br />

graduate studies <br />

Please visit our webpage h


The InsKtute of Stem Cell Biology & RegeneraKve Medicine <br />

New Ini9a9ves: inStem Labs <br />

Jyotsna Dhawan <br />

S Ramaswamy <br />

The Ins9tute <strong>for</strong> Stem Cell Biology and Regenera9ve Medicine (inStem) is a new ini9a9ve growing in an <br />

expanded campus with NCBS. In the previous pages you have seen a diversity of research programs <br />

across the scale of the Life <strong>Sciences</strong> in the laboratories of principal inves9gators. InStem aims to <br />

complement this approach by developing teams to researchers to address important ques9ons in <br />

biomedical sciences and human biology. InStem’s research is currently structured into four teams with <br />

two others coming by soon. <br />

inStem teams are composed of senior, intermediate and early career scien9sts and the <br />

scien9sts themselves are a mix of researchers, technology developers and clinicians. Team members are <br />

drawn from inStem, NCBS and elsewhere. Students wishing to rotate in these teams will be associated <br />

with an appropriate inves9gator in a team at inStem. If they would like to work <strong>for</strong> their PhD in a team <br />

project at inStem are expected to have a principal NCBS mentor. <br />

Current inStem teams along with the names of some members, who can outline research <br />

in their teams are given below. The teams are dynamic, both in their composi9on and science, so do be <br />

in touch with Jyotsna Dhawan (jdhawan@ncbs.res.in) and Apurva Sarin (sarina@ncbs.res.in) <strong>for</strong> updates <br />

and <strong>for</strong> introduc9ons to the contacts listed below. <br />

Understanding Pluripotency, Development and Regenera9on: This team aims to use <br />

induced pluripotent stem-­‐cells (iPS cells), embryonic stem (ES) cells and model organisms (mouse, fly, <br />

fish, planarian and hydra) to decipher developmental and regenera9on principles. Contact: Jyotsna <br />

Dhawan <br />

Cardiac and Vascular biology. This team studies human cardiomyopathy across scale, from <br />

molecular, cellular to 9ssue levels. They study how mutant actomyosin motors can lead to disease, how <br />

these are organized and func9on in cardiac cells and how these cells func9on in the heart. Vascular <br />

biology and ques9ons in blood development and angiogenesis are another theme. Contact: John Mercer <br />

Epithelial Biology and Skin Differen9a9on. This team, star9ng in August 2012, will uses <br />

accessible stem cell niches in skin to understand the biology of 9ssue-­‐renewal in diseases such as <br />

diabetes and eczemas. Human and mouse models will be used. Contact: Colin Jamora <br />

Chemical Biology of Cancer: This project will combine cell-­‐biology, imaging technologies, <br />

small-­‐molecule screens and structural biology to expand and define the ‘drug-­‐able’ space in specific <br />

cancer. In addi9on, several collabora9ons across the campus on the more general theme of cancer <br />

biology are being embarked. <br />

Contact: Ashok Venkitaraman <br />

Two new teams, one in the Neurobiology of Au9sm Spectrum Disorders and another in <br />

Physical Biology are likely to evolve in the coming year.


New Ini9a9ves: The Theory Program <br />

What is the theory program? <br />

NCBS is pleased to announce new PhD and IntPhD opportuni9es in the physical and mathema9cal study of biological systems. <br />

Biology, all the way from molecules, through cells, 9ssues, networks in the brain, to ecosystems holds great promise today <strong>for</strong> <br />

bright young theorists. Exci9ng problems abound, a vibrant and connected global community of theorists is growing and the thrill <br />

of conceptual discoveries await the prepared and well-­‐trained student. The theory program is open to students with a physics/<br />

maths/chemistry/engineering background and a strong curiosity in biology, as well as students with a biology background having a <br />

strong interest in the mathema9cal and computa9onal study of living systems. <br />

Faculty members with strong bonds to theory are Aswin Seshasayee (computa9onal and func9onal genomics of bacterial gene <br />

regula9on), Madan Rao (physics of ac9ve, evolving systems), Madhusudhan Venkadesan (morphology and control in animals and <br />

machines), Mukund ThaLai (computa9onal cell biology and evolu9on), Sandeep Krishna (decisions, feedback and games in <br />

biological systems), Sanjay Sane (the physics and neurobiology of insect flight), Shachi Gosavi (computa9onal protein dynamics, <br />

folding and func9on), R. Sowdhamini (computa9onal approaches to protein science) and Upinder Bhalla (computa9onal <br />

neuroscience and systems biology of olfac9on and memory). Several others colleagues collaborate with theorists and with those <br />

who model biological systems. <br />

What is unusual about this program? <br />

Crea9ng and finding new problems is an essen9al part of all scien9fic research. We put developing this skill at the heart of our <br />

program design. Students will learn to create, select and solve research problems at the interface of biology and other sciences. <br />

They are encouraged to chart their own research path in conjunc9on with faculty of the theory group. Educa9on extends beyond <br />

the classroom and good theory and prac9ce are intertwined. We encourage students to try their hand at designing small <br />

experiments -­‐-­‐ biological, electromechanical and computa9onal -­‐-­‐ in laboratories maintained by faculty associated with the theory <br />

group. We have a strong visitor program with researchers from all over the world regularly spending a few days to a few months <br />

at the group. Each student can choose to spend 6 months in a research group outside NCBS, or in industry, to give a broader <br />

perspec9ve on ways of prac9sing science and to help in<strong>for</strong>m their future career choices. <br />

What is the curriculum? <br />

We provide core courses to establish a rigorous founda9on in mathema9cal and numerical analysis, and cover topics including <br />

sta9s9cal mechanics and so[ maLer physics, molecular dynamics, stochas9c processes, nonlinear dynamics, control and <br />

op9miza9on, in<strong>for</strong>ma9on theory, and so on. Bridging courses in both basic biology and basic mathema9cs will ensure that the core <br />

courses are accessible to all. Based on students' needs we also offer advanced courses on mul9disciplinary topics like non-­equilibrium<br />

sta9s9cal mechanics, complex networks, evolu9onary dynamics, biorobo9cs and func9onal genomics. Bangalore has <br />

an excellent diverse environment <strong>for</strong> theory: Students can complement NCBS courses with those from surrounding ins9tutes such <br />

as the Indian Ins9tute of Science, Raman Research Ins9tute and the Jawaharlal Nehru <strong>Centre</strong> <strong>for</strong> Advanced Scien9fic Research, all <br />

of with whom we have ac9ve interac9ons.


Deepa Agashe <br />

Selected Publica9ons <br />

Falk JJ, Parent CEP, Agashe D and Bolnick DI <br />

(2012). Asymmetrical reproduc9ve isola9on <br />

due to maladapta9on during an <br />

experimentally induced niche shi[ in <br />

laboratory popula9ons of Tribolium <br />

castaneum. In press, EvoluKonary Ecology <br />

Research <br />

Agashe D and Bolnick DI (2012). Dietary niche <br />

and popula9on dynamic feedbacks in a novel <br />

habitat. Oikos 121(3): 347-­‐356. <br />

Agashe D, Falk JJ and Bolnick DI (2011). Effects <br />

of founding gene9c varia9on on adapta9on to <br />

a novel resource. EvoluKon 65(9): 2481-­‐2491 <br />

Agashe D and Bolnick DI (2010). Intraspecific <br />

gene9c varia9on and compe99on interact to <br />

facilitate niche expansion. Proceedings of the <br />

Royal Society of London, series B. 277(1696): <br />

2915-­‐2924 <br />

Agashe D (2009). The stabilizing effect of <br />

intraspecific gene9c varia9on on popula9on <br />

dynamics in novel and ancestral habitats. <br />

American Naturalist 174(2): 255-­‐267. <br />

EvoluKonary ecology of adaptaKon and genome evoluKon <br />

new labs at NCBS <br />

My research is largely focused on understanding the evolu9onary and ecological processes <br />

underlying adap9ve evolu9on. Adapta9on to various ecological factors has been an important <br />

<strong>for</strong>ce in the evolu9on of the amazing array of species on earth. However, we are only beginning <br />

to address some key ques9ons about adapta9on. How do ecological condi9ons (e.g. resource <br />

availability) and gene9c factors (e.g. gene9c diversity) determine the basis and dynamics of <br />

adapta9on? At the molecular level, what is the nature of selec9on on genome structure (e.g. <br />

arrangement of genes on chromosomes) and composi9on (e.g. GC%)? Conversely, how do <br />

these genomic characteris9cs affect adapta9on? My favourite approach to address these <br />

ques9ons has been experimental evolu9on in the lab. For instance, previously I tested how <br />

gene9c diversity in Tribolium beetle popula9ons affected compe99on, popula9on size, <br />

ex9nc9on, and adapta9on to new habitats. In later work, I tested how synonymous muta9ons <br />

in enzyme-­‐coding genes affect bacterial fitness, and determined the gene9c basis of <br />

subsequent adapta9on in these mutants with genome re-­‐sequencing. <br />

Looking ahead, I am star9ng two major projects at our new lab at NCBS. First, I <br />

want to determine the ecological and gene9c factors that determine a species’ range, which <br />

remains poorly understood <strong>for</strong> most species. We will analyze dispersal, adap9ve poten9al, <br />

resource availability, and gene9c popula9on structure in Tribolium castaneum popula9ons <br />

across India as a comprehensive example of the processes that shape an organism’s <br />

distribu9on. Second, we don’t quite understand the <strong>for</strong>ces responsible <strong>for</strong> the evolu9on of <br />

major genomic features such as GC content and codon usage, and their impact on adapta9on. <br />

To address this, we will manipulate these genomic features in gene9cally tractable bacteria <br />

(e.g. Escherichia coli), and using bioin<strong>for</strong>ma9c and phylogene9c methods to test the generality <br />

of our experimental results. <br />

To summarize, we would like to 9nker with gene9c and ecological features of <br />

organisms so that as we watch evolu9on in ac9on, we can beLer understand how it works.


Krushnamegh Kunte <br />

EvoluKon and organizaKon of biological diversity <br />

new labs at NCBS <br />

Research in my lab is aimed at understanding the evolu9on and organiza9on of biological diversity on <br />

earth. As a lab, we study biodiversity in an interdisciplinary manner, with our scien9fic ques9ons <br />

spanning the fields from community and popula9on ecology to evolu9onary gene9cs, and methods <br />

ranging from behavioral experiments to phylogene9c inference, theore9cal modeling, and molecular and <br />

developmental gene9c experiments. Our work addesses aspects of the origin of species, morphological <br />

diversifica9on, and ecological and molecular gene9c bases of sex-­‐limited and polymorphic traits. We try <br />

to integrate the fields of popula9on biology, natural selec9on theory and molecular gene9cs, which <br />

serves to conceptually unify the biological sciences. <br />

Recent Publica9ons <br />

Kunte, K., C. Shea, M. L. Aardema, J. M. <br />

Scriber, T. E. Juenger, L. E. Gilbert, and <br />

M. R. Kron<strong>for</strong>st. 2011. Sex chromosome <br />

mosaicism and hybrid specia9on among <br />

9ger swallowtail buLerflies. PLoS <br />

Gene)cs, 7:e1002274. <br />

Tiple, A., D. Agashe, A. M. Khurad and K. <br />

Kunte. 2009. Popula9on dynamics and <br />

seasonal polyphenism of Chilades <br />

pandava buLerfly (Lycaenidae) in <br />

central India. Current Science, <br />

97:1774-­‐1779. <br />

Kunte, K. 2009. Female-­‐limited mime9c <br />

polymorphism: A review of theories and <br />

a cri9que of sexual selec9on as <br />

balancing selec9on. Animal Behaviour, <br />

78:1029–1036. <br />

Kunte, K. 2009. The diversity and <br />

evolu9on of Batesian mimicry in Papilio <br />

swallowtail buLerflies. Evolu)on, <br />

63:2707–2716. <br />

Kunte, K. 2008. Mime9c buLerflies <br />

support Wallace's model of sexual <br />

dimorphism. Proceedings of the Royal <br />

Society, B, 275:1617-­‐1624. <br />

We primarily use two systems as microcosms to study biodiversity. The first system is <br />

Batesian mimicry, which is a phenomenon whereby unprotected prey species (called “mimics”) gain <br />

protec9on from predators by mimicking toxic or otherwise protected species (called “models”). <br />

Predators learn to avoid models based on prior experience, and subsequently avoid ea9ng mimics due to <br />

misiden9fica9on. Hundreds of mime9c buLerfly species are known from tropical <strong>for</strong>ests. There is <br />

tremendous varia9on in the nature of Batesian mimicry: mimicry can be sexually monomorphic, <br />

polymorphic or sex-­‐limited within and across species. Our work aims to understand the selec9ve <br />

pressures that favor such varia9on in mimicry, and uncover the gene9c basis of color paLern varia9on. <br />

We mainly use phylogene9c methods, ecological observa9ons and molecular gene9c tools in this part of <br />

our research. <br />

Our second system is Indian buLerflies, which offer many opportuni9es to study <br />

biogeography, community ecology, popula9on biology and conserva9on issues. Indian buLerflies are <br />

excellent to study various interes9ng phenomena, including large-­‐scale migra9ons and seasonal <br />

polyphenism. Due to their considerable diversity and endmism in the Indian Subcon9nent, they are also <br />

outstanding subjects to study origins of species, and biogeography and phylogeography in the Oriental <br />

Region. Finally, due to increasing human pressures, the persistence of biodiversity is under threat, and <br />

buLerflies are no excep9on. The problems of a very large human popula9on in a developing country, <br />

combined with a serious administra9ve commitment to conserva9on and strong na9onal conserva9on <br />

legisla9on, makes India a unique country to understand scien9fic and social issues related to the <br />

preserva9on of biodiversity. <br />

Thus, the long-­‐term goal of our “Biodiversity Lab” is to study mechanisms that facilitate <br />

morphological diversifica9on, processes that shape the origins and dispersion of species, and the means <br />

to preserve biodiversity. You can find out more about the lab at hLp://biodiversitylab.org.


Madhusudhan Venkadesan <br />

Control and Morphology Lab <br />

Our lab is interested in the interac9on between control and morphology in animals <br />

and machines. We combine biological, mechanical, and mathema9cal methods to <br />

study how animals control their limbs and body to interact with the surrounding. <br />

Selected Publica9ons: <br />

M. Venkadesan and F.J. Valero-­‐Cuevas. <br />

Effects of neuromuscular lags on <br />

controlling contact transi9ons. Philos <br />

Trans R Soc London, Ser A, 367(1891):<br />

1163–1179, 2009. <br />

M. Venkadesan and F.J. Valero-­‐Cuevas. <br />

Neural control of mo9on-­‐to-­‐<strong>for</strong>ce <br />

transi9ons with the finger9p. Journal of <br />

Neuroscience, 28(6):1366-­‐1373, 2008. <br />

M. Venkadesan, J. Guckenheimer, and F.J. <br />

Valero-­‐Cuevas. Manipula9ng the edge of <br />

instability. Journal of Biomechanics, <br />

40(8):1653–1661, 2007. <br />

D.E. Lieberman, M. Venkadesan, W.A. <br />

Werbel, A.I. Daoud, S. D’Andrea, I.S. Davis, <br />

R.O. Mang’eni, I. Pitsiladis. Foot strike <br />

paLerns and collision <strong>for</strong>ces in habitually <br />

barefoot versus shod runners. Nature, <br />

463(7280):531–5, 2010. <br />

Humans and other animals exhibit astoundingly versa9le and robust <br />

motor behaviour. Nevertheless, there are limits to their capabili9es like when an <br />

experienced runner loses balance and falls, or even mild neuromuscular diseases <br />

have surprisingly severe effects. How are these limits of per<strong>for</strong>mance affected by <br />

disease, age, training, or ontogeny? Do animals outper<strong>for</strong>m their robo9c <br />

counterparts because of or despite the nonlineari9es and `sloppiness' inherent to <br />

biology? Have animals finely-­‐tuned their sloppiness through evolu9on in order to <br />

achieve the robustness one associates with biology? Can we, and how do we extract <br />

design and control principles <strong>for</strong> understanding biomechanical func9on and also <strong>for</strong> <br />

improving the state of modern robo9cs? Such ques9ons about animals and <br />

machines, ranging in scale from collec9ons of muscle fibres to the whole organism, <br />

are at the heart of our research. <br />

We study the dynamics and control of the hand, arm and leg, on scales <br />

ranging from collec9ons of muscle fibres to the whole animal. Biomechanical <br />

experiments with muscle recordings, kinema9cs and kine9cs are complemented by <br />

theore9cal approaches stemming from nonlinear dynamical systems, probability <br />

theory, op9miza9on theory, and numerical analysis. In parallel, bio-­‐inspired <br />

mechanical designs test our mathema9cal theories of motor control. Our ef<strong>for</strong>ts are <br />

aimed at gaining fundamental insights about how biology deals with compe9ng <br />

demands on motor behaviour. We hope that this understanding will shed light on <br />

how diseases impair our func9oning, and thus help improve treatments, surgical <br />

techniques, design of prosthe9cs, rehabilita9on regimens, and also the design of <br />

robots.


Aswin Sai Narain Seshasayee <br />

ComputaKonal and funcKonal genomics of bacterial gene <br />

regulaKon and adaptaKon <br />

Lab retreat at Wynaad <br />

Recent Publica9ons <br />

Kahramanoglou C, Prieto AI, Khedkar S, Haase B, Gupta A, <br />

Benes V, Fraser GM, Luscombe NM*, Seshasayee ASN*. <br />

Genomics of DNA cytosine methyla9on in Escherichia coli <br />

reveals its role in sta9onary phase transcrip9on. Nature <br />

CommunicaKons 2012. In Press. <br />

Seshasayee ASN*, Singh P, Krishna A. Context-­‐dependent <br />

conserva9on of DNA methyltransferases in bacteria. <br />

Nucleic Acids Research 2012. In Press. <br />

Mar9ncorena I*, Seshasayee ASN, Luscombe NM*. <br />

Evidence of non-­‐random muta9on rates suggests an <br />

evolu9onary risk management strategy. Nature 2012. In <br />

Press.[PMID: 22522932] <br />

Prieto AI, Kahramanoglou C, Ali RM, Fraser GM*, <br />

Seshasayee ASN*, Luscombe NM*. Genomic analysis of <br />

DNA bingind and gene regula9on by homologous <br />

nucleoid-­‐associated proteins IHF and HU in Escherichia <br />

coli. Nucleic Acids Research 2012. In Press. [PMID: <br />

22180530] <br />

Kahramanoglou C, Seshasayee ASN#, Prieto AI, Ibberson <br />

D, Schmidt S, Zimmermann J, Benes V, Fraser GM*, <br />

Luscombe NM*. Direct and indirect effects of H-­‐NS and Fis <br />

on global gene expression control in Escherichia coli. <br />

Nucleic Acids Research 2011. 39: 2073-­‐2091. [PMID: <br />

21097887] <br />

Bacteria are the most numerous among free-­‐living life on earth. They <br />

adapt to their environment, including a variety of stresses, by changes <br />

to their gene9c material and / or altera9ons in the nature and amounts <br />

of proteins produced. Our lab is interested in studying these aspects of <br />

bacterial biology using a combina9on of molecular and 'genomic' <br />

experiments and computa9onal analysis. In par9cular, we study the <br />

following: <br />

the role of global transcrip9onal regulators in influencing growth <br />

physiology of E. coli <br />

gene9c and transcrip9onal adapta9on of E. coli popula9ons to <br />

chemical and nutrient stresses <br />

computa9onal analysis of molecular mechanisms influencing-­‐ and <br />

consequences of horizontal gene transfer <br />

We expect an incoming PhD student to be competent in computa9on <br />

and sta9s9cs and be able to develop an independent research plan <br />

within the ambit of our group's interests. <br />

*corresponding author(s) <br />

#joint first author


Sandeep Krishna <br />

In<strong>for</strong>maKon, Decisions and Feedback in <strong>Biological</strong> Systems <br />

I'm interested in how biological organisms acquire and process in<strong>for</strong>ma9on, and integrate <br />

different pieces of in<strong>for</strong>ma9on to make decisions. I use computa9onal modeling and <br />

theore9cal analyses to understand the role of feedback mechanisms in regulatory networks <br />

that process in<strong>for</strong>ma9on. <br />

Selected Publica9ons <br />

Pedersen, L, Jensen, M. H. & <br />

Krishna, S (2011), PLoS One 6, <br />

e25550. <br />

Hunziker, A., Tuboly, C., <br />

Horvath, P., Krishna, S. & <br />

Semsey, S. (2010), Proc. Natl. <br />

Acad. Sci. (USA) 107, 12998–<br />

13003 <br />

Avlund, M., Dodd, I., Sneppen, <br />

K. & Krishna, S. (2009) J. Mol. <br />

Biol. 394, 681–693. <br />

Avlund, M., Dodd, I., Semsey, <br />

S., Sneppen, K. & Krishna, S. <br />

(2009) J. Virol. 83, 11416–<br />

11420. <br />

Krishna, S., Semsey, S. & <br />

Jensen, M. H. (2009) Phys. Biol. <br />

6, 036009. <br />

1. Bacteriophage lysis-­‐lysogeny decision. Temperate bacteriophage are amongst the simplest <br />

organisms that could be said to make a developmental decision. Upon infec9ng a bacterium, <br />

temperate phage enter either the ly9c pathway, where they replicate rapidly and eventually <br />

lyse the host, or the lysogenic pathway, where they insert their DNA into the genome of the <br />

cell and lay dormant. I’m interested in understanding how in<strong>for</strong>ma9on such as the number of <br />

infec9ng phage, bacterial growth rate, bacterial density, etc., is used to bias the lysis-­‐lysogeny <br />

decision. <br />

2. Metabolism in prokaryotes. Sugar uptake and metabolism networks in bacteria are ideal <br />

systems to study feedback. Typically, they have two entangled feedback loops, a posi9ve one <br />

regula9ng transport and a nega9ve one regula9ng metabolism. In contrast, iron metabolism in <br />

several bacteria has at its core two nega9ve feedback loops. I’m interes9ng in understanding <br />

the dynamics of mul9ple entangled loops by inves9ga9ng compara9ve models of metabolic <br />

regula9on in E. coli, H. pylori and Y. pes9s, and mapping the transi9on to sta9onary phase in <br />

bacteria growing on single carbon sources. More generally, I would like to uncover principles <br />

that can be used to predict the behaviour of combina9ons of feedback loops. <br />

3. Oscillatory control in signaling systems. Periodic behaviour in cells covers a wide range of <br />

9mescales, from circadian rhythms (24 hours) to calcium oscilla9ons (seconds). Oscilla9ons of <br />

1-­‐5 hour 9me periods have been observed in NF-­‐kB, p53 and Wnt signaling, which are, <br />

respec9vely, crucial regulators of immune response, cell growth/death and embryo <br />

development. Yet, the precise role of oscilla9ons is unclear. I use theore9cal models to explore <br />

whether in<strong>for</strong>ma9on about the s9muli that trigger NF-­‐kB, p53 and Wnt can be encoded in <br />

characteris9cs of oscilla9ons, e.g. their frequency.


Vatsala Thirumalai <br />

Selected Publica9ons: <br />

Marder E and Thirumalai V (2002) <br />

Cellular, synap9c and network <br />

effects of neuromodula9on. Neural <br />

Networks 15(4-­‐6):479-­‐93. <br />

Thirumalai V, Prinz AA, Johnson, CD <br />

and Marder E (2006) Red Pigment <br />

Concentra9ng Hormone Strongly <br />

Enhances the Strength of the <br />

Feedback to the Pyloric Rhythm <br />

Oscillator but Has LiLle Effect on <br />

Pyloric Rhythm Period. J. <br />

Neurophysiol., 95(3):1762-­‐70. <br />

Thirumalai V and Cline HT (2008) A <br />

commanding control of behavior. <br />

(2008) Nat Neurosci. 11(3):246-­‐8. <br />

Thirumalai V and Cline HT (2008) <br />

Endogenous dopamine suppresses <br />

ini9a9on of swimming in pre-­‐feeding <br />

zebrafish larvae. J. Neurophysiol. <br />

100(3):1635-­‐48. <br />

Neural control of movement during development and in adulthood <br />

For most animal species, survival depends cri9cally on the ability to move-­‐ be it <strong>for</strong> <br />

feeding, escaping predators or selec9ng a suitable mate. To generate movement, <br />

skeletal muscles need to be contracted in precisely coordinated paLerns. Neural circuits <br />

control the spa9al and temporal paLern of skeletal muscle contrac9ons. Our lab is <br />

interested in understanding the hierarchy, mechanisms and development of neural <br />

circuits that generate movement. <br />

In vertebrates, the circuits that control movement are found in the spinal <br />

cord and in the brain. The spinal circuits controlling the genera9on of locomo9on are <br />

referred to as ‘central paLern generators’ as the output from these circuits is <br />

paLerned and rhythmic electrical ac9vity sent to the muscles. These central paLern <br />

generators are in turn controlled by sensory drive and by commands from the <br />

locomotory centers of the brain. My lab focuses on the development of central paLern <br />

generators and the development of descending motor control from the brain. We also <br />

seek to understand the mechanisms by which brain locomotor circuits control <br />

movement in mature organisms. <br />

We use zebrafish, a small fresh water tropical fish endemic to the Ganges, <br />

as our model system. The embryonic and larval stages of these fish are transparent <br />

allowing <strong>for</strong> direct visual observa9on of developing internal organs including the brain. <br />

We employ a suite of techniques to tease out the circuitry responsible <strong>for</strong> genera9ng <br />

swimming in developing and more mature zebrafish. We record electrical ac9vity from <br />

individual spinal and brain neurons using extracellular and whole-­‐cell patch clamp <br />

techniques. We record ac9vity from popula9ons of neurons simultaneously using <br />

calcium imaging. We generate transgenic zebrafish to express proteins of interest in <br />

par9cular neurons. This allows us to selec9vely ablate and also to electrically ac9vate/<br />

inac9vate specific popula9ons at will. Using these cu ng edge tools and technologies, <br />

we hope to throw light on the development of neural circuits and the neural basis of <br />

locomo9on.


Shachi Gosavi <br />

Selected Publications:<br />

D. T. Capraro, M. Roy, J. N. Onuchic, S. <br />

Gosavi, and P. A. Jennings,“ β-­‐Bulge <br />

triggers route-­‐switching on the <br />

func9onal landscape of interleukin-­‐1β.” <br />

Proc. Natl. Acad. Sci. USA, 109, <br />

1490-­‐1493, 2012. <br />

P. C. Whiƒord, J. K. Noel, S. Gosavi, A. <br />

Schug, K. Y. Sanbonmatsu and J. N. <br />

Onuchic, “An All-­‐atom Structure-­‐Based <br />

Poten9al <strong>for</strong> Proteins: Bridging Minimal <br />

Models with All-­‐atom Empirical <br />

Forcefields.” Proteins, 75, 430-­‐441, <br />

2009. <br />

S. Gosavi, P. C. Whiƒord, P. A. Jennings <br />

and J. N. Onuchic, “Extrac9ng func9on <br />

from a b-­‐trefoil folding mo9f.” Proc. <br />

Natl. Acad. Sci. USA, 105, 10384-­‐10389, <br />

2008. <br />

L. L. Chavez, S. Gosavi, P. A. Jennings and <br />

J. N. Onuchic, “Mul9ple routes lead to <br />

the na9ve state in the energy landscape <br />

of the b-­‐trefoil family.” Proc. Natl. Acad. <br />

Sci. USA, 103, 10254-­‐10258, 2006. <br />

S. Gosavi, L. L. Chavez, P. A. Jennings and <br />

J. N. Onuchic, “Topological Frustra9on <br />

and the folding of Interleukin-­‐1b.” J. <br />

Mol. Biol., 357, 986-­‐996, 2006. <br />

ComputaKonal folding and funcKonal dynamics of proteins <br />

Proteins are the workers of the cell. It is important to be able to both predict and engineer <br />

their func9on. The na9ve or folded shape of a protein, (as seen in the crystal or NMR <br />

structure) is essen9al <strong>for</strong> this func9on. Also, proteins are constantly moving and jiggling <br />

and these dynamics aid binding and con<strong>for</strong>ma9onal change. So, protein mo9on, both <br />

large-­‐scale folding as well as small scale local vibra9ons, facilitates protein func9on. <br />

The same amino acid sequence helps the protein both fold efficiently and a[er <br />

folding, work accurately. So, protein folding and protein func9on are interconnected. For <br />

example, one can’t engineer func9on without aLen9on to folding because this can <br />

destabilize the protein, and one can’t increase folding rates by changing func9onal <br />

residues. I am interested in understanding this tradeoff between folding and func9on using <br />

computa9onal methods. <br />

Computa9onal molecular dynamics (MD) provides a detailed descrip9on of <br />

protein mo9on not easily accessible to experimental methods. Protein dynamics occur on <br />

diverse 9mescales but o[en it is only the low frequency (long 9mescale) mo9on that is <br />

func9onally relevant. Including all atoms of the protein in a model restricts the maximum <br />

allowed simula9on 9mescale and gives an incomplete descrip9on of the func9onal mo9on. <br />

One solu9on to the 9mescale problem is the simplifica9on of the interac9on between <br />

atoms and I use a class of models called the structure-­‐based models to per<strong>for</strong>m my MD <br />

simula9ons. <br />

I intend to use two families of proteins as a test bed <strong>for</strong> my studies. One of <br />

them is the β-­‐trefoil family of proteins. Proteins from this family are interes9ng because <br />

they all have the same core structure but they per<strong>for</strong>m different binding func9ons in <br />

different organisms. They also fold very slowly. The main ques9on is whether their slow <br />

folding can be related to their func9on. <br />

The second set of proteins that I intend to work on is a family of protease <br />

inhibitors called the serpins. These are big proteins (350+ residues), which require a large <br />

shape change be<strong>for</strong>e they can func9on. I want to understand the interplay between the <br />

shape change and the folding of these proteins.


Raghu Padinjat <br />

Selected publica9ons <br />

Raghu, P., Yadav, S and Mallampa9, N. (2012) <br />

Lipid signalling in Drosophila photoreceptors. <br />

Biochimica et Biophysica Acta -­‐ Molecular and <br />

Cell Biology of Lipids. Vesicular Transport. (in <br />

press) <br />

Georgiev, P., et.al (2010). TRPM channels <br />

mediate zinc homeostasis and cellular growth <br />

during Drosophila larval development. Cell <br />

Metabolism. 12, 386–397 <br />

Raghu, P, et.al (2009) Rhabdomere biogenesis <br />

in Drosophila photoreceptors is acutely <br />

sensi9ve to phospha9dic acid levels. Journal of <br />

Cell Biology 185 129-­‐145 <br />

Raghu P, Hardie RC. 2009 Regula9on of <br />

Drosophila TRPC channels by lipid messengers. <br />

Cell Calcium. 45(6):566-­‐73. <br />

Garcia-­‐Murillas I, et.al (2006) Iazaro encodes a <br />

lipid phosphate phosphohydrolase that <br />

regulates phospha9dylinositol turnover during <br />

Drosophila phototransduc9on. Neuron. 29:4, <br />

533-­‐546. <br />

The architecture of phosphoinosiKde signalling in vivo <br />

Our long term scien9fic interest is the analysis of signalling mediated by lipid <br />

molecules generated during phosphoinosi9de metabolism. Phosphoinosi9de signals <br />

provide molecular control <strong>for</strong> key sub-­‐cellular processes such as membrane <br />

remodelling, cytoskeletal func9on, transcrip9on and transla9on. Through these <br />

processes, this signalling pathway orchestrates basic cellular behaviours such as cell <br />

division, shape changes, polarized movement and cell death. The overall goal of our <br />

work is to understand how the architecture this signalling cascade is designed to <br />

deliver op9mal physiological outputs. We use the fruit fly Drosophila as our model <br />

system; the goal is to discover key principles of signal transduc9on that are likely to <br />

be conserved during evolu9on but are experimentally more tractable in Drosophila. <br />

Phospha9dylinositol 4,5 bisphosphate [PI(4,5)P2] is a phosphoinosi9de <br />

with mul9ple, key cellular func9ons. Despite the widespread use of PI(4,5)P2 as a <br />

signalling substrate, its levels in animal cells are stable and demonstrable changes <br />

during normal cell signalling are at best minimal. In order to 9ghtly regulate <br />

PI(4,5)P2 levels, it is essen9al <strong>for</strong> cells to closely monitor PI(4,5)P2 levels at the <br />

plasma membrane and to closely match the rate of PI(4,5)P2 resynthesis with its <br />

consump9on by signalling reac9ons. We are studying the mechanisms by which <br />

PI(4,5)P2 levels are regulated in the context of Drosophila phototransduc9on, a <br />

process that depends cri9cally on PI(4,5)P2 hydrolysis and during which the <br />

turnover of this lipid is 9ghtly regulated (Hardie and Raghu, 2001). <br />

A second area of research is the analysis of cellular growth during <br />

larval development. We have recently iden9fied a novel phosphoinosi9de kinase <br />

that appears essen9al <strong>for</strong> larval growth and works thorough the evolu9onarily <br />

conserved growth regulator TOR. Several exci9ng projects are available in both the <br />

above areas. They involve a mixture of modern Drosophila molecular gene9cs, lipid <br />

biochemistry, cell biology and in vivo live imaging both in cells and in the intact <br />

organism.


Deepak T. Nair <br />

Molecular determinants of genomic integrity and plasKcity <br />

Recent Publica9ons: <br />

Amit Sharma, Vidya Subramanian and Deepak T. Nair. <br />

The PAD region in the mycobacterial dinB homolog <br />

MsPolIV exhibits posi9onal heterogeneity Acta <br />

Crystallogr D Biol Crystallogr. 2012 (in press). <br />

Amit Sharma and Deepak T. Nair, “MsDpo4—a DinB <br />

Homolog from Mycobacterium smegma9s—Is an Error-­‐<br />

Prone DNA Polymerase That Can Promote G:T and T:G <br />

Mismatches,” Journal of Nucleic Acids, vol. 2012, <br />

Ar9cle ID 285481, 2012. <br />

Amit Sharma and Deepak T. Nair. Cloning, expression, <br />

purifica9on, crystalliza9on and preliminary <br />

crystallographic analysis of MsDpo4: a Y-­‐family DNA <br />

polymerase from Mycobacterium smegma9s. Acta <br />

Crystallogr Sect F Struct Biol Cryst Commun. 2011 Jul <br />

1;67(Pt 7):812-­‐6. <br />

Sivakumar Namadurai*, Deep9 Jain*, Dhananjay S. <br />

Kulkarni*, Chaitanya R. Tabib, Peter Friedhoff, Desirazu <br />

N Rao and Deepak T Nair. The C-­‐terminal domain of the <br />

MutL homolog from Neisseria gonorrhoeae <strong>for</strong>ms an <br />

inverted homodimer. PLoS One. 2010 Oct <br />

28;5(10):e13726. (* equal contribu9on) <br />

The blueprint of life <strong>for</strong> each organism is resident in its genome. Nucleic <br />

acid metabolizing enzymes play cri9cal roles in ensuring proper <br />

in<strong>for</strong>ma9on transfer from the genome <strong>for</strong> synthesis of effector <br />

molecules. Members of this broad group of enzymes are also <br />

instrumental in the maintenance of the genome. Perturba9on in the <br />

func9on of these enzymes due to muta9ons or inhibitors has an adverse <br />

effect on the survival of the organism. A chemical and topological <br />

descrip9on of enzymes in their func9onal state – in the <strong>for</strong>m of three-­dimensional<br />

structures-­‐ has always provided important insights into the <br />

mechanism of their ac9on and the molecular basis of related diseases. <br />

In my laboratory we are using this approach to study three <br />

processes involving the ac9on of nucleic acid metabolizing enzymes on <br />

the genome. These processes are (a) DNA Mismatch repair (b) DNA <br />

damage tolerance and (c) Japanese Encephali9s Virus Replica9on. Using <br />

X-­‐ray crystallography as the primary tool in conjunc9on with relevant <br />

biochemical methods and allied biophysical techniques, we aim to <br />

provide structural insight into the mechanism of ac9on of enzymes/<br />

enzyme complexes that are cri9cal in each of these processes. Through <br />

ongoing and new collabora9ve ef<strong>for</strong>ts, we aim to shed more light on the <br />

rela9on between biochemical and structural proper9es of these enzymes <br />

and their observed and predicted roles in physiology.


Sanjay P. Sane <br />

Selected Publica9ons: <br />

Singh, A.K, Prabhakar, S and Sane, S. <br />

P.* (2011). The biomechanics of fast <br />

prey capture by aqua9c bladderworts. <br />

Biology Lecers, 7, 547-­‐550. <br />

Sane S.P.*, Srygley R.B., Dudley R. <br />

(2010) Antennal regula9on of <br />

migratory flight in the neotropical moth <br />

Urania fulgens, Biology Lecers 6: <br />

406-­‐409 <br />

Sane SP* and McHenry MJ (2009) The <br />

biomechanics of sensory organs, <br />

IntegraKve and ComparaKve Biology, <br />

49(6):i8-­‐i23; <br />

Sane, S.P.*, Dieudonne, A., Willis, M. A. <br />

and Daniel, T. L. (2007). Antennal <br />

mechanosensors mediate flight control <br />

in moths. Science 315, 863-­‐866. <br />

Sane, S. P. (2003). The aerodynamics of <br />

insect flight. Journal of Experimental <br />

Biology, 206, 4191-­‐4208. <br />

Neural and physical basis of insect flight <br />

The spectacular evolu9onary success of insects owes much to the evolu9on of flight. <br />

Insect flight is characterized by speed, control and manoeuvrability. Their wings flap <br />

at very rapid rates (typically on the order of 10-­‐100 Hz) and hence their sensory <br />

system must acquire and process in<strong>for</strong>ma9on at similar rates. How do the nervous <br />

systems of insects tackle the extraordinary challenges of acquiring, integra9ng and <br />

processing mul9modal sensory in<strong>for</strong>ma9on and genera9ng of rapid behavioural <br />

responses to ensure stable flight? Our laboratory combines inputs from diverse <br />

disciplines such as physics, biomechanics, neurobiology and behaviour to address <br />

this ques9on. <br />

Broadly speaking, our approach involves the iden9fica9on and <br />

measurement of interes9ng flight behaviours in diverse insect taxa (Diptera, <br />

Hymenoptera, Lepidoptera), and the dissec9on of their physical and sensorimotor <br />

machinery to understand the mechanisms underlying these behaviours. On the <br />

physical front, we combine aerodynamic studies on flapping wings with high-­‐speed <br />

videographic measurements of wing mo9on to understand how flapping wings <br />

generate and modulate aerodynamic flight <strong>for</strong>ces to determine their aerial <br />

trajectories. On the neurobiological front, we are inves9ga9ng the combined role of <br />

vision and mechanosensa9on in flight control in insects, including the neural <br />

pathways that integrate and process these mul9-­‐sensory inputs. More recently, we <br />

have also begun specific inves9ga9ons on insect flight in their natural context. These <br />

include specific projects on insect-­‐plant interac9ons, as well as inves9ga9ons of <br />

longer-­‐scale flight phenomena such as long distance migra9on and dispersal. <br />

Together, these studies are aimed to provide a broader level picture of insect flight <br />

from neurons and physiology to ecology. In addi9on to the above, we are also <br />

beginning new projects to study the physics and biology of termite mound <br />

architecture in the coming years.


Mahesh Sankaran <br />

Community and Ecosystems Ecology <br />

Selected Publica9ons : <br />

Higgins, S.I., Scheiter, S. & Sankaran, M. <br />

(2010). The stability of African savannas: <br />

insights from the indirect es9ma9on of the <br />

parameters of a dynamic model. Ecology. <br />

91(6):1682-­‐92 <br />

Sankaran, M. (2009). Diversity paLerns in <br />

savanna grassland communi9es: implica9ons <br />

<strong>for</strong> conserva9on strategies in a biodiversity <br />

hotspot. Biodiversity & ConservaKon 18: <br />

1099-­‐1115. <br />

Ratnam, J., Sankaran, M., Hanan N. P., Grant, <br />

R. C & Zamba9s, N. (2008). Nutrient <br />

resorp9on paLerns of plant func9onal groups <br />

in a tropical savanna: varia9on and func9onal <br />

significance. Oecologia 157 (1): 141 – 151 (doi: <br />

10.1007/s00442-­‐008-­‐1047-­‐5). <br />

Sankaran, M., Ratnam, J & Hanan, N. P.(2008). <br />

Woody cover in African savannas: the role of <br />

resources, fire and herbivory. Global Ecology <br />

& Biogoegraphy. 17: 236 -­‐ 245. <br />

Sankaran, M., et al. (2005). Determinants of <br />

woody cover in African savannas. Nature 438: <br />

846 -­‐ 849. <br />

My research interests span two broad areas of ecology: plant-­‐herbivore-­‐soil <br />

interac9ons and biodiversity-­‐ecosystem func9on rela9onships. <br />

Current research in the lab is grouped around three themes that examine <br />

• How interac9ons and feedbacks between climate, biogeochemistry, fires <br />

and herbivory influence the structure, composi9on and stability of ecosystems and <br />

the cycling and sequestra9on of nutrients. <br />

• The role of species diversity in regula9ng ecosystem func9on and <br />

provisioning of ecosystem services to humans. <br />

• How projected changes in climate such as increasing variability of rainfall, <br />

increased frequency of droughts, increasing aridity in the tropics, nitrogen and <br />

phosphorus deposi9on and rising CO2 will impact ecosystem func9on, stability and <br />

services. <br />

Our current and planned future work will address the above ques9ons <br />

across the gamut of natural ecosystem types of the Indian sub-­‐con9nent, with the <br />

goal of bringing a comprehensive understanding of biome-­‐scale vegeta9on and <br />

nutrient dynamics in the sub-­‐con9nent. Most of our research thus far has been <br />

carried out in savanna ecosystems in Africa. Besides being economically important <br />

biomes, savannas are also perfect model systems <strong>for</strong> the kinds of research ques9ons <br />

that we are interested in. We are now extending this work to savanna ecosystems in <br />

India, but also expanding to encompass a wider range of ecosystem types including <br />

rain<strong>for</strong>ests and grasslands. Addi9onally, recognizing that much of the terrestrial sub-­con9nent<br />

is 9ed up in agricultural ecosystems, the dynamics of which will play a <br />

cri9cal role in our ability to cope with changes in climate regimes and provide food <br />

security in the coming decades, we are now also expanding into this area.


Dominik Schwudke <br />

Linking biological phenotypes to their chemical basis <br />

Selected Publica9ons: <br />

Entchev, E.V., Schwudke, D., Zagoriy, V., Matyash, V., <br />

Bogdanova, A., Habermann, B., Zhu, L., Shevchenko, A. <br />

and Kurzchalia (2008). TV. LET-­‐767 is required <strong>for</strong> the <br />

produc9on of branched chain and long chain faLy acids in <br />

C. elegans. Journal of Biochemistry, 283, 17550-­‐17560. <br />

Matyash, V., Liebisch, G., Kurzchalia, T.V., Shevchenko, A. <br />

and Schwudke, D. (2008), Lipid extrac9on by methyl-­‐tert-­butyl<br />

ether <strong>for</strong> high-­‐throughput lipidomics. Journal of <br />

Lipid Research 49, 1137-­‐1146. <br />

Graessler J #, Schwudke D #, Schwarz PE, Herzog R, <br />

Shevchenko A, and Bornstein SR. Top-­‐down lipidomics <br />

reveals ether lipid deficiency in blood plasma of <br />

hypertensive pa9ents. PLoS One. 2009 Jul 15;4(7):e6261. <br />

Carvalho, M.; Schwudke, D.; Sampaio, J. L.; Palm, W.; <br />

Riezman, I.; Dey, G.; Gupta, G. D.; Mayor, S.; Riezman, H.; <br />

Shevchenko, A.; Kurzchalia, T. V.; Eaton, S., Survival <br />

strategies of a sterol auxotroph. Development 2010, 137 <br />

(21), 3675-­‐3685. <br />

Herzog R#, Schwudke D# , Schuhmann K, Sampaio JL, <br />

Bornstein SR, Schroeder M and Shevchenko A. A novel <br />

in<strong>for</strong>ma9cs concept <strong>for</strong> high-­‐throughput shotgun <br />

lipidomics based on the molecular fragmenta9on query <br />

language Genome Biol. 2011 Jan 19;12(1):R8. [Epub <br />

ahead of print] # These authors contributed equally to <br />

this work. <br />

Interdisciplinary inves9ga9ons at the interface of biology and <br />

analy9cal chemistry are my personal interest, which focused on <br />

development and applica9on of mass spectrometric methods <strong>for</strong> <br />

biological research. <br />

In par9cular, I will inves9gate cell and 9ssue <br />

differen9a9on during development of D. melanogaster with <br />

lipidomics and proteomics approaches. In all higher organism cells <br />

take diverse func9onal responsibili9es. In that regard it can be <br />

observed that cells, <strong>for</strong>ming specialized 9ssues, contain specific <br />

lipidomes. Interes9ngly, func9ons and specific lipid composi9ons are <br />

assigned during embryogenesis and we do not fully understand how <br />

this is happening. From this perspec9ve we want to learn how, when <br />

and where specific lipidomes are established in the course of 9ssue <br />

differen9a9on.


Mukund ThaLai <br />

ComputaKonal and evoluKonary cell biology <br />

Recent Publica9ons: <br />

Rai N, Anand R, Ramkumar K, <br />

Sreenivasan V, Dabholkar S, Venkatesh <br />

KV, ThaLai M (2012) Predic9on by <br />

promoter logic in bacterial quorum <br />

sensing. PLoS Comput. Biol. 8: <br />

e1002361. <br />

Anand R, Rai N, ThaLai M (2011) <br />

Promoter reliability in modular <br />

transcrip9onal networks. Methods <br />

Enzymol. 497: 31. <br />

Ramadas R, ThaLai M (2010) Flipping <br />

DNA to generate and regulate microbial <br />

consor9a. GeneKcs 184: 285. <br />

Callahan B, ThaLai M, Shraiman BI <br />

(2009) Emergent gene order in a model <br />

of modular polyke9de synthases. Proc. <br />

Natl. Acad. Sci. USA 106: 19410. <br />

Though cells are the basic units of all living things, we know remarkably <br />

liLle about their ac9vity and evolu9on. At the same 9me, new experiments <br />

are genera9ng a torrent of data about the structure and interac9ons of the <br />

bio-­‐molecules from which cells are made up. We seek to bridge the gap: <br />

going from molecules to cellular phenotypes. What makes this enterprise <br />

exci9ng is that a complex system can have proper9es different from those <br />

of its cons9tuent parts. We study the molecular basis of the emergent <br />

proper9es of two cellular systems: the network of factors that turn gene <br />

transcrip9on on and off; and the complex trafficking of materials between <br />

the mul9tude of intracellular compartments. <br />

Our work involves a close interplay between simple <br />

mathema9cal models and quan9ta9ve experiments: we use techniques <br />

borrowed from control theory and electrical engineering to design and <br />

experimentally test synthe9c transcrip9onal networks built from well-­understood<br />

molecular components in bacterial cells; and we use <br />

biophysical models to explore how organelles and traffic arise from basic <br />

molecular interac9ons in eukaryo9c cells. Ul9mately, cells are products of <br />

basic evolu9onary <strong>for</strong>ces: muta9on and recombina9on which act on <br />

molecules; selec9on and dri[ which act on phenotypes and popula9ons. <br />

Studying the emergence of phenotype from molecular interac9ons will be <br />

essen9al if we are to understand the deep evolu9onary origins of modern <br />

cells.


Yamuna Krishnan <br />

Structure and dynamics of Nucleic acids <br />

Recent Publica9ons: <br />

Chakraborty, S., Mehtab, S., Patwardhan, A.R., Krishnan, Y.* <br />

(2012) Pri-­‐miR-­‐17-­‐92a Transcript folds into a ter9ary <br />

structure and autoregulates its processing. RNA 18, <br />

1014-­‐1028. <br />

Saha, S., Chakraborty, K. and Krishnan, Y*. (2012) Tunable, <br />

colorimetric DNA based pH sensors mediated by A-­‐mo9f <br />

<strong>for</strong>ma9on. Chem. Commun. 48, 2513. <br />

Bha9a, D., Sharma, S. and Krishnan, Y*. (2011) Synthe9c, <br />

biofunc9onal nucleic acid-­‐based molecular devices. Curr <br />

Opin Biotechnol, 22, 475-­‐484. <br />

Modi, S. and Krishnan, Y.* (2011) A method to map <br />

spa9otemporal pH changes insde living cells using a pH <br />

triggered DNA nanoswitch. Methods Mol. Biol. 749, 61-­‐77. <br />

Surana, S., Bhat, J.M., Koushika, S.P. and Krishnan, Y.* (2011) <br />

An autonomous DNA nanomachine maps spa9otemporal pH <br />

changes in a mul9cellular living organism. Nature <br />

CommunicaKons, 2, 340. <br />

Bha9a, D., Surana, S., Chakraborty, S., Koushika, S.P. and <br />

Krishnan, Y.* (2011) A synthe9c, icosahedral DNA-­‐based <br />

host-­‐cargo complex <strong>for</strong> func9onal in vivo imaging. Nature <br />

CommunicaKons, 2, 339. <br />

Krishnan, Y and Simmel, F. C. (2011) Nucleic Acid Based <br />

Molecular Devices. Angew. Chem. Int. Ed. 50, 3124-­‐3156. <br />

Bionanotechnology aims to learn from nature -­‐ to understand the <br />

structure and func9on of biological devices and to u9lise nature's <br />

solu9ons in advancing science and engineering. Evolu9on has <br />

produced an overwhelming number and variety of biological devices <br />

that func9on at the nanoscale or molecular level and whose <br />

per<strong>for</strong>mance is unsurpassed by man-­‐made technologies. My lab uses <br />

chemical and biophysical tools to explore structure and dynamics in <br />

nucleic acid assemblies with a view to exploi9ng the knowledge gained <br />

<strong>for</strong> applica9ons in biology. <br />

With a diameter of 2 nm and a helical periodicity of 3.5 <br />

nm, the DNA double helix is inherently a nanoscale object. The <br />

specificity of Watson-­‐Crick base pairing endows oligonucleo9des with <br />

unique and predictable recogni9on capabili9es. This makes DNA an <br />

ideal nanoscale construc9on material. Understanding and thereby <br />

controlling structure and dynamics in designed DNA assemblies is key <br />

to realizing DNA’s poten9al as a nanoscale building block. <br />

We make DNA based molecular assemblies <strong>for</strong> <br />

applica9ons as fluorescent sensors of second messengers in-­‐cellulo <br />

and in-­‐vivo. Another area of interest involves understanding naturally <br />

occurring RNA structural mo9fs and how they impact RNA processing.


Uma Ramakrishnan <br />

Natural environments around us are changing at unprecedented rates. As wildlands <br />

shrink, human popula9ons increase and the temperature escalates, we scramble to <br />

understand how the species around us will respond. We hope that such understanding <br />

will aid in stewarding species survival in the future. Integral to this stewardship are the <br />

fields of ecology and evolu9on, and I focus on this research interface. I study the <br />

processes governing the response of species to environmental history, clima9c <br />

perturba9on and human history in the context of species ecologies, and hence gain a <br />

beLer understanding of their evolu9on. <br />

Recent Publica9ons: <br />

ChaLopadhyay, B, Garg, KM, Vinoth Kumar, AK, <br />

Swami Doss, DP, Ramakrishnan, U & Kandula, S. <br />

Sibling species in the south Indian popula9ons of <br />

Rufous horse-­‐shoe bat, Rhinolophus rouxii (in press, <br />

ConservaKon GeneKcs) <br />

Robin VV, Sinha A & Ramakrishnan, U (2010) Ancient <br />

Geographical Gaps and Paleo-­‐climate Shape the <br />

Phylogeography of an Endemic Bird in the Sky Islands <br />

of Southern India. PLoS ONE 5(10): e13321. doi:<br />

10.1371/journal.pone.0013321. <br />

O’Keefe, K, Ramakrishnan, U, van Tuinen, M & Hadly, <br />

EA. Source-­‐sink dynamics in a common montane <br />

mammal (2009) Molecular Ecology, 18(23):<br />

4775-­‐4789. <br />

Mondol, S, et al (2009a) Evalua9on of non-­‐invasive <br />

gene9c sampling methods <strong>for</strong> es9ma9ng 9ger <br />

popula9on size. <strong>Biological</strong> ConservaKon, <br />

142:2350-­‐2360. <br />

Mondol, S, Karanth, KU, Ramakrishnan, U (2009b) <br />

Why the Indian subcon9nent holds the key to global <br />

9ger recovery. PLoS GeneKcs, 5(8):e1000603. <br />

In prac9cal terms, my research focuses on revealing the processes that <br />

drive paLerns of mammalian gene9c varia9on (in the present and the past). I use field-­collected<br />

samples, assemble molecular gene9c data and analyze these data with <br />

phylogene9c, phylochronologic, phylogeographic and popula9on gene9c inferences. Much <br />

of my research over the last few years has focused on the Indian subcon9nent because of <br />

(1) its geographic se ng, represen9ng the intersec9on of three major biogeographic <br />

realms (Palearc9c, Africotropical, Indomalayan); (2) its geologically drama9c history, <br />

driven by plate tectonics, volcanism and clima9c change; (3) its ecologically diverse habitat <br />

types from the highest mountains on earth to very dry deserts and tropical <strong>for</strong>ests, <br />

including biodiversity hotspots; (4) the presence of Homonins in India <strong>for</strong> perhaps one <br />

million years, and modern humans in rela9vely high (and ever increasing) densi9es <strong>for</strong> <br />

about 70,000 years impac9ng the Indian biota; and finally the fact that (5) virtually <br />

nothing is known about paLerns of gene9c varia9on in na9ve Indian species, and even <br />

less is known about the impact of climate on species in this region in par9cular. <br />

Broadly, the research in my laboratory can be divided into three types of <br />

ques9ons: (1) What drives paLerns of diversity in the Indian subcon9nent? (2) What are <br />

the impacts of climate on temporal changes in diversity? (3) What is the cryp9c <br />

biodiversity of India and how can we safeguard its future?


R. Sowdhamini <br />

ComputaKonal approaches to protein science <br />

Selected Publica9ons: <br />

Pugalenthi, G., Bhaduri, A. and <br />

Sowdhamini, R. (2005). genDiS: <br />

Genomic distribu9on of protein <br />

structural superfamilies. Nucleic Acid <br />

Research, 33, D252-­‐255. <br />

Chakrabar9, S. and Sowdhamini, R. <br />

(2004). Regions of minimal structural <br />

varia9on among members of protein <br />

domain superfamilies: Applica9on to <br />

remote homology detec9on and <br />

modelling using distant rela9onships <br />

FEBS Lecers, 569, 31-­‐36. <br />

Innis, C.A., Anand, OP.A. and <br />

Sowdhamini, R. (2004). Predic9on of <br />

Func9onal Sites in Proteins using <br />

Conserved Func9onal Group Analysis. <br />

Journal of Molecular biology, 337, <br />

1053-­‐1068 <br />

The knowledge-­‐based approach to protein structure-­‐and-­‐func9on <br />

predic9on exploits the property of evolu9onary convergence where it is <br />

es9mated that there is a limited number of protein folds in the en9re <br />

universe (Chothia, 1992, Nature, 357, 543-­‐544) shared by protein <br />

superfamilies. Computa9onal approaches on protein structure and <br />

func9on predic9on from mere sequence in<strong>for</strong>ma9on should be of value to <br />

address the vast amount of data emerging from genome projects and <strong>for</strong> <br />

the ra9onal design of high-­‐throughput experiments. Sowdhamini and her <br />

group have contributed to the following major areas: <br />

(i) development and maintenance of rela9onal and sub-­‐derived databases <br />

(ii) development of algorithms and approaches <strong>for</strong> the sensi9ve detec9on <br />

of puta9ve members of protein families and superfamilies <br />

(iii) development of equipment and so[ware <strong>for</strong> genome-­‐wide surveys of <br />

protein families, cross-­‐genome surveys and calcula9on of diversity <br />

measures <br />

(iv) construc9on of protein func9onal templates useful <strong>for</strong> func9on <br />

predic9on <br />

(v) development of improved homology modeling during distant <br />

rela9onship with structural homologues.


Sumantra (Shona) ChaLarji <br />

SynapKc plasKcity in the amygdala: implicaKons <strong>for</strong> stress & <br />

auKsm spectrum disorders <br />

Selected Publica9ons <br />

Roozendaal, B.l, McEwen, B.S., & ChaLarji, S. (2009) <br />

Stress, Memory and the amygdala. Nature Reviews <br />

Neuroscience 10: 423-­‐433. <br />

Suvrathan, A., Hoeffer, C. A., Wong, H., Klann, E., <br />

and ChaLarji, S. (2010) Characteriza9on and reversal <br />

of synap9c defects in the amygdala in a mouse <br />

model of fragile X syndrome. Proc. Natl. Acad. Sci. <br />

USA 107 (25): 11591-­‐11596. <br />

Suvrathan, A. and ChaLarji, S. (2011) Fragile X <br />

Syndrome and the Amygdala. Current Opinion in <br />

Neurobiology, 21 (3): 509-­‐515. <br />

Malik, R. and ChaLarji, S. (2012) Enhanced intrinsic <br />

excitability and EPSP-­‐spike coupling accompany <br />

enriched environment induced facilita9on of LTP in <br />

hippocampal CA1 pyramidal neurons. Journal of <br />

Neurophysiology, 107 (5): 1366-­‐1378. <br />

Rao, R.P., Anilkumar, S., McEwen, B.S., and <br />

ChaLarji, S. (2012) Glucocor9coids protect against <br />

the delayed behavioral and cellular effects of acute <br />

stress on the amygdala. <strong>Biological</strong> Psychiatry (in <br />

press). <br />

Memories come in many different flavors, some more potent than others. <br />

Emo9onally significant experiences tend to be well remembered, and the <br />

amygdala has a pivotal role in this process. But the rapid and efficient <br />

encoding of emo9onal memories can become maladap9ve — severe stress <br />

o[en turns them into a source of chronic anxiety. What are the cellular <br />

mechanisms underlying these powerful emo9onal symptoms? To answer <br />

this ques9on, we have been using a range of behavioral, morphometric, in <br />

vitro and in vivo electrophysiological tools to iden9fy neural correlates of <br />

stress-­‐induced modula9on of amygdala structure and func9on — from <br />

cellular and synap9c mechanisms to their behavioural consequences in <br />

rodents. Our findings point to unique features of stress-­‐induced plas9city <br />

in the amygdala, which are in striking contrast to those seen in the <br />

hippocampus and cortex, and could have long-­‐term consequences <strong>for</strong> <br />

pathological fear and anxiety exhibited in people with affec9ve disorders. <br />

In addi9on to behavioral experience, the genes we inherit can <br />

also cause cogni9ve and emo9onal dysfunc9on. Strikingly, individuals <br />

afflicted with certain types of au9sm spectrum disorder o[en exhibit <br />

impaired cogni9ve func9on alongside high anxiety and mood lability. <br />

Hence, we are extending our analyses to gene9cally engineered mice to <br />

iden9fy cellular and molecular targets that can be used to correct <br />

symptoms of Fragile X Syndrome, the leading gene9c cause of au9sm.


Apurva Sarin <br />

RegulaKng cell number in mulK-­‐cellular organisms <br />

Selected Publica9ons <br />

Perumalsamy LR et al., (2009) A hierarchical cascade <br />

ac9vated by non-­‐canonical Notch signaling and the <br />

mTOR -­‐ Rictor complex regulates neglect-­‐induced <br />

death in mammalian cells. Cell Death & <br />

DifferenKaKon 16:879-­‐889 <br />

Purushothanam D & Sarin A (2009) Cytokine-­dependent<br />

regula9on of NADPH oxidase ac9vity and <br />

the consequences <strong>for</strong> ac9vated T cell homeostasis <br />

Journal of Experimental Medicine 206:1515-­‐23 <br />

Perumalsamy LR et al., (2010) A Notch ac9vated <br />

signaling cascade interacts with mitochondrial <br />

remodeling proteins to regulate cell survival Proc. <br />

Natl. Acad. Sc USA. 107:6882-­‐6887. <br />

Perumalsamy LR et al.,(2012) Dis9nct spa9al and <br />

molecular features of Notch pathway assembly in <br />

Regulatory T-­‐cells. Science Signaling (accepted) <br />

Garg M et al., -­‐Linker Histone H1.2 triggers apopto9c <br />

cascades integrated by the mitochondrion (submi


Upinder S. Bhalla <br />

Memory, smell, and networks <br />

Selected Publica9ons: <br />

Khan, A.G., Sarangi, M., Bhalla, U.S. Rats <br />

track odour trails accurately using a mul9-­‐<br />

layered strategy with near-­‐op9mal sampling. <br />

Nature CommunicaKons. 3(703), doi:<br />

10.1038/ncomms1712, 2012. <br />

Ramakrishnan, N., Bhalla, U.S., Tyson, J.J. <br />

Compu9ng with proteins. Computer 42(1):<br />

47-­‐56, doi:10.1109/MC.2009.12 <br />

Bhalla, U.S. How to Record a Million <br />

Synap9c Weights in a Hippocampal Slice. <br />

Public Library of Science: ComputaKonal <br />

Biology. 4(6): e1000098, 2008. <br />

Khan, A.G., ThaLai, M., and Bhalla, U.S. <br />

Odor Representa9ons in the Rat Olfactory <br />

Bulb Change Smoothly with Morphing <br />

S9muli. Neuron. 57(4):571-­‐85, 2008. <br />

!<br />

If we could take a picture of a memory, what would it look like? How do you store <br />

the memory of a fragrance, or of how to ride a bicycle? We are working on the idea <br />

that memories are stored in the paLern of connec9ons between brain cells. To <br />

store memories in this manner, the brain must convert in<strong>for</strong>ma9on into ac9vity <br />

paLerns, modify connec9ons, and stably retain these modifica9ons. Our research <br />

covers each of these topics. <br />

First, we monitor cellular ac9vity in the hippocampus of mice as they <br />

learn to associate a sound or other sensory s9mulus with a subsequent puff or air. <br />

We do these recordings in the rat hippocampus, a region of the brain involved in <br />

memory. This lets us get a picture of how the ac9vity and connec9ons change in <br />

real 9me, as the animal learns. <br />

Second, by systema9cally s9mula9ng input cells and monitoring which <br />

cells they influence, we can build up connec9on diagrams that define what <br />

memories have already been encoded. Building on advances in microscopy, we can <br />

monitor ac9vity of hundreds of cells using chemical sensors whose light emission <br />

changes when a cell is ac9ve. We use electrical and op9cal triggers to carry out the <br />

s9mulus, again poten9ally scaling to hundreds of inputs. <br />

Third, the connec9ons need to be stable to store in<strong>for</strong>ma9on <strong>for</strong> a long <br />

9me. This is very hard to do, because each connec9on, or synapse, is so small that a <br />

rela9vely small number of individual molecules must do all the work and withstand <br />

thermal noise, turnover, and chemical insults. We probe events at these 9ny scales <br />

using both experiments and computer models. We are developing powerful <br />

so[ware tools to model how these events are orchestrated. This so[ware, MOOSE, <br />

runs on laptops as well as giant Unix-­‐based supercomputers. <br />

Overall, our work falls into the domains of systems biology and <br />

computa9onal neuroscience, with a lively mix of experiments and computer <br />

modeling. Our lab includes people from physics, chemistry, mathema9cs, biology, <br />

computer science and other branches of engineering.


Satyajit Mayor <br />

!<br />

Selected Publica9ons <br />

Gowrishankar, K, et al, (2012). Ac9ve <br />

remodeling of cor9cal ac9n regulates <br />

spa9otemporalorganiza9on of cell <br />

surface molecules. Cell in press. <br />

Howes, M., Mayor, S. and Parton, R. <br />

(2010). Molecules, mechanisms, and <br />

cellular roles of clathrin-­‐independent <br />

endocytosis. Curr Opin Cell Biol ;22(4):<br />

519-­‐27. <br />

Vyas, N., et al., (2008). Nanoscale <br />

organiza9on of hedgehog is essen9al <br />

<strong>for</strong> long-­‐range signaling. Cell, 133(7), <br />

1214-­‐27. <br />

Goswami, D., et al., (2008). <br />

Nanoclusters of GPI-­‐anchored proteins <br />

are <strong>for</strong>med by cor9cal ac9n-­‐driven <br />

ac9vity. Cell. 135(6), 1085-­‐97. <br />

Kumari, S., et al. (2008). Nico9nic <br />

acetylcholine receptor is internalized <br />

via a Rac-­‐dependent, dynamin-­independent<br />

endocy9c pathway. J Cell <br />

Biol 181, 1179-­‐1193. <br />

Mechanisms of membrane organizaKon and traffic <br />

The broad aim of my laboratory is to develop an understanding of how a cell regulates the local <br />

organiza9on of its cell surface cons9tuents. This will help in understanding how a eukaryo9c cell <br />

constructs signaling complexes (composi9on) and also how it may engage in de<strong>for</strong>ming its membrane <br />

(endocytosis) in a regulated fashion. To study phenomena at the cellular scale, principles from the <br />

physical sciences provide a powerful paradigm in framing ques9ons about the mechanisms of movement <br />

of molecules and organelles inside cells. Consequently, in my laboratory we have taken a mul9-­‐<br />

disciplinary approach, combining biology with physics and chemistry to address the main theme of our <br />

research. <br />

We have developed new microscopy technologies to study nanometer scale organiza9on <br />

of cellular components, and explored the organiza9on and dynamics of fluorescently-­‐tagged molecules in <br />

a variety of living cells, including stem cells; from the nanometer scale in specialized domains in cell <br />

membranes to the micron scale prevalent in mapping endocy9c pathways. We also study sor9ng <br />

proper9es and endocy9c pathways of a variety of molecules, including membrane proteins, lipids and <br />

lipid-­‐tethered proteins in vivo. Our studies provide a new picture of the cell membrane as an ac9ve <br />

composite of the lipid bilayer and a dynamic cor9cal ac9n layer beneath, wherein, dynamic ac9n <br />

filaments help in controlling the local composi9on of membranes. <br />

We are now involved in several specific lines of inquiry. These include; i) theore9cal and <br />

experimental studies on the basis <strong>for</strong> the <strong>for</strong>ma9on of membrane ra[s in living cells (in collabora9on <br />

with Madan Rao, NCBS, RRI); ii) exploring the dynamics of such membrane complexes during signaling <br />

and templated differen9a9on in mul9ple cell systems, including stem cells; ii) understanding the ac9ve <br />

organiza9on of many cell surface proteins including the Acetylcholine receptor modula9on (in <br />

collabora9on with Prof. Francisco Barrantes, INIBIB, Bahia Blanca, Argen9na), the T-­‐ Cell Receptor (in <br />

collabora9on with Ron Vale, UC at San Francisco, USA), and integrins; iii) scales of organiza9on in the <br />

func9oning of cholesterol-­‐tethered Hedgehog in paLerning 9ssues in situ, in collabora9on with RS. <br />

Sowdhamini, NCBS; iii) molecular mechanism of dynamin-­‐independent endocytosis using cell-­‐based <br />

assays at the individual gene scale, and genome wide-­‐RNAi screening methods (in collabora9on with <br />

Mukund ThaLai, NCBS); iv) understanding the roles of different endocy9c pathways in paLerning 9ssues <br />

in the animal, in collabora9on with Prof. KS Krishnan, NCBS, and K. Vijayraghavan, NCBS; <br />

The trajectory of this work has led us to explore the fine structure of the plasma <br />

membrane, providing <strong>for</strong> the first 9me an in vivo picture of lipidic assemblies challenging exis9ng no9ons <br />

of membrane ra[s, an understanding of the role of specialized endocy9c mechanisms <strong>for</strong> the <br />

establishment of developmental gradients, and a genome-­‐wide analysis of endocy9c pathways.


Sudhir Krishna <br />

Notch signalling in human epithelial cancers and leukemias: <br />

A research program based in both NCBS and St. John’s Medical <br />

College <br />

Selected Publica9ons: <br />

Maliekal TT, Bajaj J, Giri V, Subramanyam D, Krishna S. <br />

(2008).The role of Notch signaling in human cervical cancer: <br />

implica9ons <strong>for</strong> solid tumors. Oncogene; 27(38):5110-­‐4. <br />

Srivastava S, Ramdass B, Nagarajan S, Rehman M, <br />

Mukherjee G, Krishna S.(2010). Notch1 regulates the <br />

func9onal contribu9on of RhoC to cervical carcinoma <br />

progression. Br J Cancer. 102(1):196-­‐20 <br />

Rangarajan A, Talora C, Okuyama R, Nicolas M, Mammucari <br />

C, Oh H, Aster JC, Krishna S, Metzger D, Chambon P, Miele <br />

L, Aguet M, Radtke F, DoLo GP. (2001). Notch signaling is a <br />

direct determinant of kera9nocyte growth arrest and entry <br />

into differen9a9on. EMBO J. 20(13):3427-­‐36. <br />

Rangarajan A, Syal R, Selvarajah S, Chakrabar9 O, Sarin A, <br />

Krishna S. (2001). Ac9vated Notch1 signaling cooperates <br />

with papillomavirus oncogenes in trans<strong>for</strong>ma9on and <br />

generates resistance to apoptosis on matrix withdrawal <br />

through PKB/Akt. Virology. 286(1):23-­‐30. <br />

Bajaj, J., Maliekal., TT., Vivien, E., PaLabiraman, C., <br />

Srivastava, S., Krishnamurty, H., Giri, V., Subramanyam, D & <br />

Krishna, S (2011). Notch signaling in CD66+ cells drives the <br />

progression of human cervical cancers. Cancer Research, <br />

71, 4888-­‐97. <br />

Our lab has <strong>for</strong> some 9me now been interested in the role of Notch <br />

signalling in human epithelial cancers. We have focussed our analysis on <br />

human cervical cancer-­‐ a tumour ini9ated and sustained by oncogenically <br />

high risk Human Papillomaviruses. Our recent work has led to the <br />

iden9fica9on of a sub-­‐set of cells (Bajaj, Maliekal et al., Cancer Research <br />

2011) that has features of cancer stem like cells and is dependent on <br />

Notch signaling. Our major collabora9ve hospital in this programe so far <br />

has been the Kidwai Memorial Ins9tute of Oncology. <br />

Department of Biotechnology Glue grant inita)ve: <br />

We have been awarded a major 5 year grant to co-­‐develop laboratory <br />

facili9es at St. John’s Medical College. In addi9on to the exis9ng research <br />

infrastructure in St. John’s Medical College, we are developing molecular <br />

biology and 9ssue culture labs along with a flow cytometry and imaging <br />

facility. From NCBS, Drs. Sweta Srivastava and H. Krishnamurty are some <br />

of the key scien9sts involved in this program <br />

The St. John’s Medical college program has led to a second <br />

cancer that we are studying ie: Chronic Myeloid Leukemia (CML). Our <br />

focus is on CML stem cells and our key collaborator is Cecil Ross, a senior <br />

hematologist.


Mitradas M. Panicker <br />

Selected Publica9ons: <br />

Raote, I., BhaLacharya, A. and Panicker, M.M. (2007). <br />

Serotonin 2A (5-­‐HT2A) Receptor Func9on: Ligand-­‐<br />

Dependent Mechanisms and Pathways. In Serotonin <br />

Receptors in Neurobiology. FronKers in Neuroscience <br />

Vol 35 Edited by A. ChaLopadhyay (Taylor and Francis, <br />

CRC Press). 105-­‐132. <br />

Basu, B., Desai, R., Balaji, J., Chaerkady,R., Sriram, V., <br />

Mai9, S., and Panicker, M.M. (2008). Serotonin in pre-­implanta9on<br />

mouse embryos is localized to the <br />

mitochondria and can modulate mitochondrial <br />

poten9al. ReproducKon. 135: 657-­‐659. <br />

Karuppiah Kanagarajadurai, Manoharan Malini, <br />

BhaLacharya Adi9, Mitradas M. Panicker and <br />

Ramanathan Sowdhamini. (2009). Molecular Modeling <br />

and docking studies of human 5-­‐hydroxytryptamine 2A <br />

(5-­‐HT2A) receptor <strong>for</strong> the iden9fica9on of hotspots <strong>for</strong> <br />

ligand binding. Molecular Biosystems 5: 1877-­‐1888. <br />

Adi9 BhaLacharya, Shobhana Sankar and Mitradas M. <br />

Panicker (2009). Differences in the C-­‐terminal tail <br />

contribute to the varia9on in trafficking between the <br />

Rat and Human 5-­‐HT2A receptor iso<strong>for</strong>ms: <br />

Iden9fica9on of a primate-­‐specific tripep9de ASK mo9f <br />

that confers GRK-­‐2 and β2-­‐Arres9n interac9on. J. <br />

Neurochem. 112: 723-­‐32. <br />

The roles of serotonin in neural and non-­‐neural systems <br />

The major interests of my laboratory are the cellular and molecular <br />

regulatory mechanisms ac9vated by serotonin, a molecule widely <br />

recognized as an important neurotransmiLer. Interes9ngly most of the <br />

serotonin is expressed outside the nervous system and seems to be involved <br />

in normal physiology in a number of ways including early development in <br />

mammals <strong>for</strong> e.g. stem cells. Most of the interac9ons of serotonin take <br />

place through its receptors i.e. protein molecules expressed on the cell <br />

surface. Among the many receptors that it interacts with, two of these i.e. <br />

the 5-­‐HT1A and 5-­‐HT2A receptors have also been strongly implicated in <br />

stress and in schizophrenia. So serotonin plays an important role in <br />

communica9on between neurons and also governs development, behavior <br />

and physiology, in fact, all aspects of an organism’s life. <br />

Our studies have primarily focused on the regula9on of 5-­‐HT2A <br />

receptors in neuronal and non-­‐neuronal cells and also on its role in early <br />

developmental processes. The 5-­‐HT2A receptor is also an important target <br />

of many clinically prescribed an9psycho9cs. Using modified 5-­‐HT2A <br />

receptors, which can be visually localized within cells, we have made <br />

significant observa9ons regarding the behavior of the receptor in the <br />

presence of serotonin and an9psycho9cs. These studies have helped us <br />

dissect the details of how these receptors are regulated by endogenous and <br />

exogenous ligands. <br />

Our recent results using pre-­‐implanta9on mouse embryos and <br />

mammalian embryonic stem cells also suggest that serotonin receptors and <br />

serotonin may play an important role in early differen9a9on. Serotonin has <br />

been localized to the mitochondria and affects mitochondrial poten9al. This <br />

has important implica9ons <strong>for</strong> development and cell survival.


Gai9 Hasan <br />

Recent Publica9ons: <br />

Agrawal, N, Padmanabhan, N and Hasan G. (2009) Inositol <br />

1,4,5 -­‐ trisphosphate Receptor Func9on in Drosophila Insulin <br />

Producing Cells. PLOS One, 4(8): e6652 <br />

Venkiteswaran, G and Hasan, G (2009). Intracellular calcium <br />

signaling and store operated Ca 2+ entry are required in <br />

Drosophila neurons <strong>for</strong> flight. Proc. Natl. Acad. Sci. USA, <br />

106, 10326-­‐10331. <br />

Agrawal, N, Venkiteswaran, G, Sadaf, S, Padmanabhan, N, <br />

Banerjee, S and Hasan, G. (2010). Inositol 1,4,5-­‐trisphosphate <br />

receptor and dSTIM func9on in Drosophila insulin producing <br />

neurons regulates systemic intracellular calcium homeostasis <br />

and flight. J. Neurosci, 30, 1301-­‐1313. <br />

Kumar, S., Dey, D and Hasan, G. (2011) PaLerns of gene <br />

expression in Drosophila InsP 3 receptor mutant larvae reveal <br />

a role <strong>for</strong> InsP 3 signaling in carbohydrate and energy <br />

metabolism. PLoS One, 6(8): e24105. doi:10.1371/<br />

journal.pone.0024105 <br />

Chorna, T and Hasan, G. (2011). The gene9cs of calcium <br />

signaling in Drosophila melanogaster. Biochem Biophys Acta <br />

doi:10.1016/j.bbagen.2011.11.002. <br />

Chakraborty S. and Hasan G. (2012). IP 3 Receptor, Store-­‐<br />

Operated Calcium Entry and neuronal calcium homeostasis in <br />

Drosophila. Biochemical Society Transac)ons 40, 279-­‐281. <br />

!<br />

Inositol 1,4,5-­‐trisphosphate signalling in cellular and <br />

systemic physiology <br />

Research in my group addresses systemic and cellular consequences <br />

of changes in intracellular calcium levels in animals. We are <br />

specifically interested in the second messenger Inositol 1,4,5-­‐<br />

trisphosphate (InsP3) and its receptor – the InsP3 receptor. This <br />

protein exists on the membranes of intracellular calcium stores and <br />

per<strong>for</strong>ms the dual func9on of a receptor <strong>for</strong> InsP3 and a channel <strong>for</strong> <br />

calcium release. We address InsP3 receptor func9on in the model <br />

organism Drosophila using gene9c, molecular, cellular, <br />

electrophysiological and behavioral methods. <br />

Our recent work has demonstrated that reducing InsP3R <br />

func9on in Drosophila neurons affects feeding and growth in larvae <br />

and mul9ple aspects of flight circuit development and func9on in <br />

pupae and adults. These studies have shown that restoring InsP3R <br />

func9on in neurons which either synthesize monoamines (like <br />

dopamine) or insulin-­‐like pep9des (ILPs) rescues InsP3R mutant <br />

defects. More recently, projects to understand how InsP3R mutants <br />

respond to changes in regula9on of intracellular store Ca2+ and to <br />

stress condi9ons (S. Manivannan, S.K. Metya, submiLed) have been <br />

ini9ated. Work from my group has demonstrated <strong>for</strong> the first 9me in <br />

a physiological context the requirement <strong>for</strong> store-­‐operated calcium <br />

entry downstream of InsP3 signaling in neurons. Results from these <br />

studies suggest that gene9c and pharmacological methods could be <br />

used <strong>for</strong> controlling intracellular Ca2+ homeostasis as a possible <br />

therapeu9c strategy in certain neurodegenera9ve and metabolic <br />

diseases. Drosophila model and human studies in the context of such <br />

diseases are in progress.


Mathew K Mathew <br />

Recent Publica9ons: <br />

Rajagopal A, Rao AU, Amigo J, Tian M, Upadhyay S, <br />

Hall C, Uhm S, Mathew MK, Fleming MD, Paw BH, <br />

Krause M & Hamza I (2008) Heme homeostasis is <br />

regulated by the conserved and concerted <br />

func9ons of HRG-­‐1 proteins Nature 453, 1127 – <br />

1131 <br />

Upadhyay SK, Nagarajan P & Mathew MK (2009) <br />

Potassium Channel Opening: A Subtle Two-­‐Step J <br />

Physiol 587, 3851–3868 <br />

Pannaga Krishnamurthy, Kosala Ranathunge, <br />

Shraddha Nayak, Lukas Schreiber & M.K.Mathew <br />

(2011) Root barriers block Na+ traffic to shoots in <br />

rice (Oryza sa9va L.) J Exp Botany 62, 4215 – 4228 <br />

Godbole A, Mitra R, Dubey AK, Reddy PS & <br />

Mathew MK (2011) Bacterial Expression, <br />

Purifica9on and Characteriza9on of a Rice Voltage <br />

Dependent Anion-­‐Selec9ve Channel Iso<strong>for</strong>m, <br />

OsVDAC4 J Membrane Biol 244, 67–80 <br />

Kavitha PG, Miller T, Mathew MK & Maathuis FJM <br />

(2012) Rice cul9vars with differing salt tolerance <br />

contain similar ca9on channels in their root cells. J <br />

Exp Botany in press doi:10.1093/jxb/ers052 <br />

Crossing Barriers: Studies of Membrane Transport <br />

<strong>Biological</strong> membranes pose a significant barrier to the movement of ions and polar <br />

molecules, requiring the ac9vity of transmembrane proteins to cross these barriers. <br />

My laboratory studies several such proteins, called transporters, ranging from the <br />

voltage-­‐gated K+ channel in neurons to transporters that play a rôle in the survival of <br />

plants in salty soils. Our aim is to understand how these proteins do their jobs and to <br />

see how their ac9vity contributes to the overall physiology of the cell or organism. <br />

The voltage-­‐gated K+ channel is involved in genera9ng Ac9on Poten9als <br />

in neurons. It senses transmembrane electric fields and opens and closes in response <br />

to changes in membrane poten9al. Star9ng with a crystal structure, we have <br />

combined computer modeling with mutagenesis and electrophysiology to come up <br />

with a detailed mechanism of how voltage drives channel opening and closing. <br />

Plants use a variety of strategies to survive in salty soil. We have shown <br />

earlier that controlling the amount of Na+ that reaches the shoot is cri9cal, as are <br />

cellular mechanisms <strong>for</strong> maintaining low Na+ levels in the cytoplasm. Barriers in the <br />

root which prevent external fluid from directly entering the xylem contribute to the <br />

ability of the plants to regulate what gets sent up to the shoot. The principal route <br />

<strong>for</strong> Na+ entry to the rice shoot appears to be by bypassing these barriers. Our data <br />

indicates that barriers are beLer developed in salt-­‐tolerant varie9es than in sensi9ve <br />

varie9es and we are inves9ga9ng the mechanisms underlying their deposi9on. <br />

At the cellular level, we have found that the plasma membranes of cells <br />

from tolerant varie9es are much less permeable to Na+ than those from sensi9ve <br />

varie9es. Tolerant varie9es also accumulate a significant amount of Na+ in their <br />

vacuoles. We are using a combina9on of molecular biology, microscopy and <br />

electrophysiology to inves9gate the basis of these differences. A study of vesicle <br />

trafficking in plant cells shows that endocytosis is drama9cally affected by salinity <br />

and suggests a plausible mechanism <strong>for</strong> maintaining a steady state in the vacuole <br />

despite “dumping” so much Na+ into it.


Jayant Udgaonkar <br />

How do proteins fold, unfold and misfold? <br />

Selected Publica9ons: <br />

Jha, S.K. & Udgaonkar, J.B. (2009) Direct <br />

demonstra9on of a dry molten globule <br />

intermediate on the unfolding pathway of a <br />

small protein. Proc. Natl. Acad. Sci. USA 106, <br />

12289-­‐12294. <br />

Aghera, N. & Udgaonkar, J.B. (2012) Kine9c <br />

studies of the folding of heterodimeric <br />

monellin: evidence <strong>for</strong> switching between <br />

alterna9ve parallel pathways J. Mol. Biol. (In <br />

press) <br />

Jain, S. & Udgaonkar, J.B. (2011) Defining the <br />

pathway of worm-­‐like amyloid fibril <strong>for</strong>ma9on <br />

by the mouse prion protein by delinea9on of <br />

the produc9ve and unproduc9ve <br />

oligomeriza9on reac9ons. Biochemistry 50, <br />

1153-­‐1161. <br />

Ramachandran, G. & Udgaonkar J. B. (2012) <br />

Evidence <strong>for</strong> the existence of a secondary <br />

pathway <strong>for</strong> fibril growth during the <br />

aggrega9on of tau. J. Mol. Biol. (In Press). <br />

The polypep9de chain of a protein must coil, turn, bend, loop and twist itself in a very <br />

precise manner while folding into the unique structure that enables the protein to func9on <br />

in the cell. The protein folding problem is to understand how structure develops as a <br />

protein folds. How proteins fold has been a long-­‐standing, unsolved puzzle in biology, <br />

whose solu9on has obvious biotechnological as well as medical implica9ons. In par9cular, <br />

the improper folding of some proteins, and their consequent aggrega9on into amyloid <br />

fibrils, are characteris9c features of several neuro-­‐degenera9ve diseases as well as of the <br />

prion diseases. An understanding of the mechanism of protein folding will also lead to a <br />

beLer understanding of the other facet of the protein folding problem, which is how to <br />

predict the func9onal structure of a protein from the amino-­‐acid sequence that specifies it. <br />

My laboratory uses several small proteins, including barstar, monellin, the <br />

SH3 domain of the PI3-­‐kinase, α-­‐synuclein, tau, and the mouse prion protein as archetypical <br />

model proteins <strong>for</strong> studying how proteins fold, unfold as well as aggregate. We also study <br />

how correct folding is assisted by the chaperone GroEL. We use the tools of protein <br />

engineering and physical biochemistry. These include diverse op9cal spectroscopic <br />

methods such as 9me-­‐resolved fluorescence methods, as well as nuclear magne9c <br />

resonance spectroscopy and mass spectrometry methods. Our kine9c measurements span <br />

the 9me domain of 100 microseconds to 10 hours. <br />

Highlights of our recent work on protein folding and unfolding include (1) the <br />

demonstra9on that a dry molten globule <strong>for</strong>ms ini9ally during unfolding; (2) the <br />

demonstra9on that the PI3 kinase SH3 domain folds and unfolds via mul9ple intermediates; <br />

and (3) the demonstra9on of switching between mul9ple folding pathways during the <br />

folding of monellin. Highlights of our recent work on protein misfolding and aggrega9on <br />

include (1) the demonstra9on that amyloid protofibrils may have different morphologies <br />

when <strong>for</strong>med on different pathways, and that a single muta9on in the protein sequence or <br />

a change in aggrega9on condi9ons can lead to switching between alterna9ve available <br />

pathways; (2) the demonstra9on that tau can u9lize a secondary pathway <strong>for</strong> amyloid <br />

fibril <strong>for</strong>ma9on; and (3) the iden9fica9on of the direct oligomeric precursor of worm-­‐like <br />

amyloid fibrils <strong>for</strong>med by the mouse prion protein.


K VijayRaghavan <br />

Developmental neurobiology of olfacKon and <br />

movement <br />

Selected Publica9ons <br />

Brierley D, Rathore K, VijayRaghavan K, Williams D. Developmental <br />

origins and architecture of Drosophila leg motoneurons. J Comp <br />

Neurol. 2011 Nov 25.doi: 10.1002/cne.23003. [Epub ahead of print] <br />

Guruharsha KG, Rual JF, Zhai B, Mintseris J, Vaidya P, Vaidya N, <br />

Beekman C,Wong C, Rhee DY, Cenaj O, McKillip E, Shah S, Stapleton <br />

M, Wan KH, Yu C, Parsa B, Carlson JW, Chen X, Kapadia B, <br />

VijayRaghavan K, Gygi SP, Celniker SE, Obar RA, Artavanis-­‐Tsakonas S. <br />

A protein complex network of Drosophila melanogaster. Cell. 2011 <br />

Oct 28;147(3):690-­‐703 <br />

Mukherjee, P., Gildor, B., Shilo, B., VijayRaghavan, K., & Schejter, E. D. <br />

(2011). The ac9n nucleator WASp is required <strong>for</strong> myoblast fusion <br />

during adult Drosophila myogenesis Development. 138(11), <br />

2347-­‐2357. <br />

Das, A., Chiang, A., Davla, S., Priya, R., Reichert, H., VijayRaghavan, K., <br />

and Rodrigues, V. (2011). Iden9fica9on and analysis of a <br />

glutamatergic local interneuron lineage in the adult Drosophila <br />

olfactory system. Neural Systems & Circuits 1, 4. <br />

Our work is aimed at understanding how circuits are put <br />

together during development to generate the animal’s <br />

behaviour. We study the development and morphogenesis of <br />

individual neural and neuromuscular circuit components. We <br />

integrate these studies with those that examine how neurons <br />

connect to <strong>for</strong>m circuits in the brain and also connect with <br />

muscles. This gives us a picture of how the ‘plumbing’ is <br />

developmentally put together. We next examine when and <br />

how func9onal proper9es of these circuits are put in place. <br />

The segmental organiza9on of the brain in the fly is <br />

remarkably similar to that of vertebrates and points to a <br />

common-­‐, rather than an independent-­‐ origin during <br />

evolu9on. This, and the conserved nature of many molecular <br />

and cellular aspects, holds out the promise of a general <br />

relevance to the understanding of how func9onal neural <br />

circuits underlying behavior are assembled during <br />

development. <br />

DuLa, D., Umashankar, M., Lewis, E. B., Rodrigues, V., VijayRaghavan, <br />

K. (2010). Hox genes regulate muscle founder cell paLern <br />

autonomously and regulate morphogenesis through motor neurons <br />

Journal of NeurogeneKcs, 24(3), 95-­‐108.


K. S. Krishnan <br />

Reent Publica9ons: <br />

Gupta K, Kumar M, Chandrashekara K, Krishnan <br />

KS, Balaram P. (2012) Combined electron <br />

transfer dissocia9on-­‐collision-­‐induced <br />

dissocia9on fragmenta9on in the mass <br />

spectrometric dis9nc9on of leucine, isoleucine, <br />

and hydroxyproline residues in Pep9de natural <br />

products. J Proteome Res. 11(2):515-­‐22. <br />

Swetha MG, Sriram V, Krishnan KS, Oorschot <br />

VM, ten Brink C, Klumperman J, Mayor S. ( 2011) <br />

Lysosomal membrane protein composi9on, <br />

acidic pH and sterol content are regulated via a <br />

light-­‐dependent pathway in metazoan cells. <br />

Traffic. 12(8):1037-­‐55. <br />

Majumder R, Krishnan KS. ( 2012) Synap9c <br />

vesicle recycling: gene9c and cell biological <br />

studies. J Neurogenet. 24(3):146-­‐57. <br />

!<br />

Research Themes <br />

A major interest in my lab is to iden9fy and characterize new neuro-­‐ac9ve <br />

compounds from a variety of organisms. These include venoms of Marine <br />

cone snails, frog skin secre9ons and wasp venoms. The highly toxic cono-­pep9des<br />

from Conus, once characterized, could be exploited as <br />

pharmacological tools in neuroscience, cell biology and in search <strong>for</strong> drugs <br />

to treat many debilita9ng diseases. We have isolated many novel pep9des <br />

from a few cone snail species collected off the shores of South Eastern <br />

India and TIFR. Mass spectrometry-­‐based de novo sequencing of venom <br />

components combined with deep sequencing RNA from the venom glands <br />

and valida9on by chemical synthesis is our main thrust. We have started <br />

iden9fying and characterizing pep9des of therapeu9c value from wasp <br />

venoms and frog skin secre9ons. We are developing several assays mainly <br />

u9lizing the power of Drosphila gene9cs, Oocyte expression of specific <br />

channel proteins and cell biology to establish protocols <strong>for</strong> ac9vity <br />

dependent purifica9on of pep9des that could be drug leads. <br />

These studies are done in collabora9on mainly with Prof. <br />

Balaram at IISc. I also ac9vely collaborate with colleagues at IISc (S Sarma, <br />

Hanumae Gowd), colleagues at NCBS (MK Mathew, S. Mayor), GKVK <br />

( Chandrasekhar Krishnappa) Annamali Univeristy (Olivia and Anthony <br />

Fernando) Andhra University( Y. P. Rao) and North Orissa ( Sushil DuLa).


O. Siddiqi <br />

GeneKc analysis of chemosensory percepKon in Drosophila <br />

Drosophila, like the Brahmin, is born twice, first from the egg as a maggot, then <br />

from the pupa as an imago. In both of its incarna9ons the fly’s olfactory behavior <br />

undergoes profound changes with age and experience. An important problem is <br />

to dis9nguish between innate and acquired behavior. This is a difficult and, in <br />

several respects, an unseLled issue. Understanding adap9ve behavior and <br />

establishing its neural correlates is the focus of our group’s interest. As a part of <br />

this ef<strong>for</strong>t we are studying learning and memory in larva and imago. <br />

Selected Publica9ons <br />

Chakraborty TS, Goswami SP, Siddiqi O <br />

(2009) Sensory correlates of imaginal <br />

condi9oning in Drosophila melanogaster. J <br />

Neurogenet.23(1-­‐2):210-­‐9. <br />

Khurana S, Abu Baker MB, Siddiqi O. <br />

(2009) Odour avoidance learning in the <br />

larva of Drosophila melanogaster. J Biosci. <br />

34(4):621-­‐31. <br />

Iyengar A, Chakraborty TS, Goswami SP, <br />

Wu CF, Siddiqi O. (2010) Post-­‐eclosion <br />

odor experience modifies olfactory <br />

receptor neuron coding in Drosophila. Proc <br />

Natl Acad Sci U S A. 107(21):9855-­‐60. <br />

Epub 2010 May 6. <br />

Chakraborty TS, Siddiqi O. (2011). Odor <br />

recep9on in antenna and antennal lobe of <br />

Drosophila. Fly (AusKn). 5(1):14-­‐7. Epub <br />

2011 Jan 1. <br />

Some years ago we began to inves9gate imaginal condi9oning, a <br />

process by which, in the first few days a[er eclosion, the fly learns to dis9nguish <br />

between aLractants and repellents. It develops aLrac9on towards chemicals to <br />

which it is exposed and an increased aversion to odors it has not experienced <br />

(these reports, 1999). Bilal Rashid, Farzana Anjum and Jawaid Ahsan have <br />

described mutants, which affect imaginal condi9oning. Tuhin Chakraborty and <br />

Sunil Prabhakar have found that imaginal condi9oning is correlated with an <br />

increased peripheral sensory response (EAG). Abu Baker and Gayatri <br />

Ranganathan have analyzed shock avoidance learning in the larva to separate <br />

various components of olfactory memory. The experiment by Annapoorna Bhat <br />

on co-­‐induc9on is our first aLempt to develop psychophysics of odor percep9on <br />

with Drosophila.


Direc:ons to the campus <br />

From City Railway Station : NCBS is to the North of Bangalore about<br />

15kms from Majestic city railway station, 9kms from Mekhri Circle and<br />

4kms <strong>for</strong>m Hebbal Blyover (besides the Blyover is the hebbal lake). Each o<br />

these is a well-­‐known landmark. Mekhri circle is a major trafBic junction<br />

From Mekhri circle take the Bellary Highway (leading to Yelahanka), go<br />

over the Hebbal Blyover and after about 4kms you reach the L&T factory on<br />

left. Next to L&T Factory is the GKVK main gate. Enter the gate and you wil<br />

see NCBS signages. Please follow the sign boards and you reach NCBS. <br />

From Airport : From the International Airport at Devanahalli, NCBS is<br />

~25kms. It takes ~45 minutes – one hour to reach NCBS from the Airport<br />

The post-­‐paid taxi facility is available on meter charges @ Rs.15/-­‐ per km<br />

(subject to Govt. regulation). Once you exit from the airport it is a long<br />

straight road <strong>for</strong> about 18kms till you reach the trafBic light near Kendriya<br />

Vihar Apartments. This is a “y” Junction. Take the straight road which is the<br />

Yelahanks bypass high way. Stay on this road. You will pass the Jakkur<br />

Flying club and at the next TrafBic Junction (Amruthahalli) take a “U” turn<br />

Drive down to a short distance and you will spot the L&T Komatsu Factory<br />

on ypur left. Adjoining this is the GKVK Campus (Gandhi Krishi Vigyan<br />

Kendra). Enter the campus and follow the signage to reach NCBS.

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