Biology at IISER Pune

Transcription

Biology at IISER Pune
2015
Design & Editing: Shanti Kalipatnapu & Nagaraj Balasubramanian
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About IISER Pune
The Indian Institute of Science Education and
skills, computational sciences, electronics
Research in Biology at IISER Pune focuses on
Research Pune is a premier institute
and instrumentation and workshop
frontier areas in Biological Sciences. We aim
dedicated to research and teaching in the
practices. IISER Pune offers advanced
for research that seamlessly integrates
basic sciences. It was established in 2006 by
teaching and research labs where students
physics, chemistry, mathematics and
the Ministry of Human Resource
have the opportunity to pursue experiments
computational sciences to answer key
Development. In 2012, it was declared as an
as well as advanced research under the
biological questions. Research in Biology at
Institute of National Importance by an Act of
mentorship of world-class faculty.
IISER Pune currently encompasses both
Parliament. As a unique initiative in science
Eventually, this should make education and
theoretical and experimental approaches to
education in India, IISER aims to be a
careers in basic sciences more exciting and
the broad areas of Systems Biology, Ecology
Science University of the highest caliber
rewarding.
and Population Dynamics, Evolutionary-
devoted to both teaching and research in a
totally integrated manner, with state-of-theart research and high quality education, thus
nurturing both curiosity and creativity.
We dedicate ourselves to learn, teach and
serve society through excellence, in
education research and public service,
Developmental Biology, Cancer Biology,
Neurobiology, Epigenetics and GeneEnvironment interactions.
create learning and a working environment
Research programs in Biology are led by 30
IISER Pune offers a 5 year BS-MS program,
based on integrity, fairness, dignity and
faculty members. The current graduate
post-bachelor Integrated PhD programs and
professionalism to provide equal
school strength is ~100 with contribution to
post-Masters PhD programs in an
opportunities for all and to develop and
research from a large number of
intellectually vibrant atmosphere of research.
encourage a sense of environmental
undergraduate students as well every
Apart from classroom instruction, IISER Pune
responsibility.
semester.
builds student skills in areas such as scientific
inquiry, problem solving, communication
www.iiserpune.ac.in
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Biology Faculty
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Graduate Students
PhD Program
Integrated PhD
Program
SAVITA SINGH
ARCHANA PAWAR
LIBI ANANDI
SHIVIK GARG
GAJANAN KENDRE
T.T. SHREE HARSHA
DEVIKA RANADE
ISHTIYAQ AHMAD
ABOLI KULKARNI
M. VIDYADHARI
AMEYA MAHAJAN
RAHUL K. JANGID
INDUMATHI PATTA
AMIT KUMAR
SIMRAN JUNEJA
ABHISHEK S. SAHASRABUDHE
RAFEEQ AHMED
SHATARUPA GANGULY
BIPASHA DEY
SHWETA TENDULKAR
PAYAL ARYA
ABHIJEET BAYANI
SUDIPTA TUNG
DEVIKA ANDHARE
SIDDHI INCHANALKAR
MITHILA HANDU
SACHIN HOLKAR
MANAWA DIWEKAR
DEVIKA BODAS
PALLAVI AGARWAL
ANIRUDDH SASTRY
NEHA NIRWAN
JYOTI BARANWAL
KRITI CHAPLOT
DHRUV MISHRA
JAY PRAKASH SHUKLA
TRUPTI THITE
MANISH KUSHWAH
MAITHILEE KHOT
AKANKSHA OJHA
SENTHILKUMAR D.
SRISHTI DAR
VIBHA SINGH
NATASHA BUWA
PRAJNA NAYAK
SNEHA BHOGALE
MANASI MUNGI
ANUSHREE CHAPHALKAR
RAUNAQ DEO
DEBAYAN SARKAR
SHRADDHA KARVE
DARSHIKA TOMER
SOUPARNA CHAKRABARTY
SAMEER THUKRAL
R. L. PRAVEENA
RINI SHAH
BHAGYASHREE KADUSKAR
MAHESH CHAND
SHRIKANT HARNE
SANKET NAGARKAR
N. BHAVANI
AYANTIKA SENGUPTA
RAVI DEVANI
YASHRAJ CHAVHAN
RUTUJA DIWAN
APARNA SHERLEKAR
MADHANAGOPAL B.
NIRAJA BAPAT
VISHAKHA KARNAWAT
RAVI UMADI
VALLARI SHUKLA
BOOMINATHAN M.
ARUN NERU B.
KRUTULA NAIR
ABHINAV PARIVESH
MANU KRISHNAN UNNI
NEELESH SONI
YOGENDRA RAMTIRTHA
RASHMI KULKARNI
MANASI GANGAN
TANUSHREE KUNDU
MADHUMITA CHAKLADAR
MANASI KULKARNI
SAMPADA MUTALIK
KUNALIKA JAIN
NARESH BABU MALLAMPATTI
SAYALI CHOWDHARY
AJAY LABADE
DNYANESH DUBAL
HARPREET SINGH KALSI
NILAM MALANKAR
ROOPALI PRADHAN
ANKITHA SHETTY
MUKUL RAWAT
NEELADRI SEN
PUNITA BATHLA
KETAKEE GHATE
SUKRUT KAMERKAR
AMARENDRANATH SOORY
RON SUNNY
SANJANA NAIR
SHUBHANKAR KULKARNI
NEHA KHETAN
DHRITI NAGAR
SWATI SHARMA
SHIKHA KALRA
CHAITANYA MUNGI
ADITI MADUSKAR
DIVYA RAO
MUKTA PALSHIKAR
YASHASWI SINGH
GUNGI AKHILA
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Scientists & Postdoctoral Fellows
JAYEETA BANERJEE
SHITAL AHALEY
SATYAJEET KHARE
ANUP GOPALAKRISHNA PILLAI
NEELESH DAHANUKAR
ULFAT BAIG
KIRTIKUMAR KHONDARE
CHANDRAMOULI REDDY
FARHAT HABIB
KAUSHIKI BISWAS
ASHOK KUMAR H.G.
AMEYA SATHE
TRESSA JACOB
ANIRBAN GUHA
UTTARA LELE
KETKI TULPULE
SHIPRA GUPTA
SRINU MEESALA
ASHWIN KELKAR
PRAMOD PATIL
MANJUNATH
SONAM MEHROTRA
BS-MS Fifth Year Project Students
SURABHI JIRAPURE
NIHARIKA SANE
SHAILENDRA KUSHWAHA
AFSAH HASAN V.P.
PRARABDHA JAGDHANE
NISARG DESAI
DIPESHWARI SHEWALE
NEHA M.
NEERAJA REVI
HIMANSHU V. RAJMANE
ABINAND REDDY K.
DINCY MARIYAM
SUPREETH K.S.
ANURAG MISHRA
KAVYA LEO VAKKAYIL
MARINA VICTOR
ABHISHEK MISHRA
RAM KRISHNA VINAYAK
VISHNU M.S.
VIRAJ DODDIHAL
YOVHAN LANDGE
ABHILESH DHAWANJEWAR
AJESH JACOB
SADHANA PANZADE
V. SAUDAMINI
POORTATA LALWANI
PRASENJEET KAWALE
P. PRIYATHAM
LOKESH PIMPALE
SATISH BODAKUNTLA
KRISHNA ANUJAN
RACHANA BHAVE
RAVINDRA P.N.
Technical & Support Staff
SANTOSH BOTRE
GETTANJALI NERURKAR
MAHESH ROTE
MRINALINI VIRKAR
PIYUSH GADEKAR
SHABNAM PATIL
KALPESH THAKERE
VIJAY VITTAL
RUPALI JADHAV
SNEHAL PATIL
MADHAV VIPRADAS
BHARGAVI NAIK
YASHWANT PAWAR
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Image: Pucadyil Lab
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Biochemistry and Biophysics
Chaitanya Athale
Jeetender Chugh
Krishna N. Ganesh
Jeet Kalia
Saikrishnan Kayarat
Gayathri Pananghat
Thomas Pucadyil
Mrinalini Puranik
Sudha Rajamani
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Self Organization and Cell Morphogenesis
Chaitanya Athale
Assistant Professor
[email protected]
Cellular morphogenesis is governed by a
Our lab attempts to use system level models
combination of genetic and physical
of reaction-diffusion and classical mechanics
processes. The physical processes that drive it
to predict the behaviour of multi-molecular
are either self-assembly dependent- template
systems. This collective behaviour has been
effects- or self-organization that relies on
shown in the past to result in counter-intuitive
collective non-linear local interactions to
results. We have developed a model
produce emergent behaviour. Our lab aims
compared to experiments with micro-
to study such self-organized collective
patterned DNA in a flow chamber
behaviour of molecules in cell-polarization
containing Xenopus egg-extract.
and decision-making and their role in
Microscopy of labeled tubulin allows us to
organogenesis.
visualize directional mobility of the star-
Chaitanya Athale obtained his PhD in Biology
in 2003 from the University of Heidelberg,
We are currently addressing cell-
Germany with a magna cum laude. He was a
morphogenesis in systems of differing
postdoctoral fellow at MGH-MIT (Boston, USA)
complexity, combining experiment and
and EMBL (Heidelberg, Germany) before
joining IISER Pune in 2009.
theory. At the smallest scale we are studying
the motor dependent movement of
shaped arrays, which is quantified in terms of
a directional motility coefficient (dmc).
Combined with simulations it leads to
unexpected phase transitions in the
movement of the asters.
centrosomal asters and their apparent
This work has implications for fertilization and
guidance towards chromatin. At a higher
cell polarization. Additionally the work on
spatial scale we are examining the role of cell
bacterial cell morphogenesis is relevant for
division and DNA replication in bacterial cell
understanding the regulatory network by
size and shape determination.
which cells appear to be robust to changes
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to changes in environment like temperature
and growth conditions. Being at the interface
of biology, physics and image-processing
gives us the ability to derive quantitative and
novel insights into biological pattern
formation.
SELECTED PUBLICATIONS
Mahajan, S. and Athale, C.A. (2012). Spatial
and temporal sensing limits of microtubule
polarization in neuronal growth cones by
intracellular gradients and forces.
Biophysical Journal 103:2432-2445
Athale, C.A. (2011). Modelling the spatial
pattern forming modules in mitotic spindle
assembly. In W. Dubitzky, J. Southgate and
H. Fuss (Eds.). Understanding the Dynamics of
Biological Systems: Lessons learned from
Integrative Systems Biology. Springer.
Athale C.A. and Chaudhari H.C. (2011).
Population length variability and nucleoid
numbers in E. coli. Bioinformatics 27:29442948.
Langevin dynamics simulations of a centrosomal
aster with microtubules fluctuating in length (dynamic
instability) were combined with a sheet of
immobilized minus-ended motors (green circles)
based on the properties of dynein. A stabilization
gradient emanating from the chromosome (grey) is
sufficient to result in directional motility of the
centrosomal aster (Athale et al. 2014 Phys. Biol.).
Scale bar corresponds to 10 micrometers.
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NMR Spectroscopy of
Biomolecules
Jeetender Chugh
Assistant Professor
[email protected]
The main research focus of this laboratory is on
there is a need to validate these ‘feasible’
various aspects of solution NMR including
structures experimentally. Experimental
theoretical design and experimental
characterization of alternative structures for
implementation of new NMR experiments to
small RNAs using state-of-the-art R1ρ NMR
probe the biophysical characteristics of RNA
relaxation dispersion experiments has been
and proteins; understanding functional aspects
done successfully but is a time consuming and
of non-coding RNAs; and structural biology of
expensive affair. Thus there is a dire need to
microRNAs and their regulation in various
formulate sequence codes that would
disease settings.
predispose the sequence towards such motions
Developing sequence codes for ms-µs
dynamics in RNA With the current plethora of
Jeetender Chugh received his doctorate in Physical
Chemistry from Tata Institute of Fundamental
structure prediction algorithms, it is possible to
and allow predicting precise sub-optimal
secondary structures without the need of
experiments.
predict sub-optimal secondary structures for a
Expanding current structural understandings of
given RNA sequence. However, the number of
miRNA biogenesis pathway All miRNAs do not
these sub-optimal secondary structures, as
follow a universal pathway for their biogenesis.
predicted by various structure prediction
Specific mechanisms in the biogenesis of
the University of Michigan where he discovered a
algorithms available, increases exponentially
individual class of miRNAs suggest multiple
new class of switches that are significantly smaller
both with increase in the number of nucleotides
opportunities for tight regulation of miRNA
in the RNA sequence and with increase in the
levels. This spectrum of distinct mechanisms is
energy range. Even though these algorithms do
widening everyday as more and more
pretty well for small RNAs and for small energy
interacting partners are being identified.
Research (TIFR), Mumbai in 2008 for research on
NMR investigations on large protein assemblies and
method developments. Between 2008 and 2012,
Chugh was a post-doctoral fellow and Lecturer at
and orders of magnitudes faster than the other
known class of RNA switches. He also studied
dynamics of fluorinated peptides in membrane
environment and live viruses by NMR. He has joined
IISER Pune in April 2013.
range,
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Although several reports emphasize on the
regulatory activities of miRNAs, very little is
known about the structural (primary, secondary
Chugh, J. Determining transient nucleic acid
or tertiary) understanding of the regulation of
structures by NMR. Chemical Biology of
miRNA expression levels and their activity.
Nucleic Acids; RNA Technologies. Springer
Therefore, understanding the conformational
2014, 181-198. (Book Chapter)
roles fundamental for these regulatory
mechanisms in the miRNA biogenesis pathway
may act as a path-breaking step for
development of new drugs based on RNAi
mechanism.
Zeng, X., Chugh, J., Casiano-Negroni, A., AlHashimi, H. M. and Brooks III, C. L. (2014).
Flipping of the ribosomal A-site adenines
provides a basis for tRNA selection. Journal of
Molecular Biology 426(19):3201-3213.
Dethoff, E. A.*, Petzold K.*, Chugh, J.*,
Casiano-Negroni, A. and Al-Hashimi, H. M.
(2012). Visualizing transient low-populated
structures of RNA. Nature 491(7426):724-728.
Dethoff, E. A.*, Chugh, J.*, Mustoe, A. M. and
Al-Hashimi, H. M. (2012). Functional complexity
and regulation through RNA dynamics. Nature
482(7385):322-330.
Bothe, J., Nikolova E., Eichhorn, C., Chugh, J.,
Hansen, A. and Al-Hashimi, H.M. (2011).
Charaterizing RNA dynamics at atomic
resolution using solution-state NMR
spectroscopy. Nature Methods 8(11):919-931.
Secondary structures of RNA distributed over the free energy space. As we go higher in
free energy, population of a particular conformation decreases while the available
conformational space and entropy increases.
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Chemical Biology of Nucleic Acids and
Peptides; DNA Nanoscience
Krishna N. Ganesh
Professor and
Director, IISER Pune
[email protected]
Krishna Ganesh received PhD degrees from
Research in our group for more than a
Aminoproline polypeptides have been
decade is focused on rational design of a
shown to undergo switching from novel beta
novel class of DNA mimics−PNA analogues,
structure in hydrophobic solvent to PPII
incorporating chiral, non-chiral
conformation in water. The alignment of
conformational constrains and cationic
cationic lysine capped nanoparticles on
substituents in backbone to make them bind
anionic DNA template in combination with
differentially to DNA/RNA, promote cell entry
electron source such as ferrocene would
and be bioviable. These attributes would
enable generation of conducting molecular
make them good candidates for the
wires and exploiting the DNA sequence
development of nucleic acid targeted
dependent self-assembly of these systems
therapeutic and diagnostic agents.
may lead to design of molecular circuits.
Recently, we have shown that PNAs carrying
Delhi University, India (1977) and from the
methylene amino side chains on backbone
University of Cambridge, UK (1980). He was at
exhibit regio- and stereo specific effects on
the Centre for Cellular and Molecular Biology,
both DNA/RNA binding and on cell uptake
Hyderabad, India as faculty for a few years
before moving to the National Chemical
Laboratory (NCL), Pune in 1987. Prof Ganesh
has been with IISER Pune since its inception in
2006 and is the first Director of the institute.
properties of derived PNAs.
Another project involves synthesis of a series
of 4-aminoproline containing collagen
mimics that form highly stable triple helices
that are stable to collagenase in order to
develop scaffolds for tissue engineering.
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Nanda, M. and Ganesh, K.N. (2012). 4(R/S)Guanidinylprolyl collagen peptides: On-resin
synthesis, complexation with plasmid DNA and
the role of peptides in enhancment of
transfection. Journal of Organic Chemistry
77:4131-4135.
Gourishankar, A. and Ganesh, K.N. (2012).
Achiral PNA anlogs that form stronger hybrids
with cDNA relative to isosequential RNA.
Artificial DNA: PNA and XNA 3:1.
Mitra, R. and Ganesh, K.N. (2011). PNAs
grafted with (α/γ, R/S)-aminomethylene
pendants: Regio and stereo specific effects on
DNA binding and improved cell uptake.
Chemical Communications 47:1198-1200.
Patwa, A.N., Gonnade, R.G., Kumar, V.A.,
Bhadbhade, M.M., Ganesh, K.N. (2010).
Ferrocene-bis(thymine/uracil) conjugates:
Base pairing directed, spacer dependent selfassembly and supramolecular packing.
Journal of Organic Chemistry 75:8705-8708.
Sonar, M.V. and Ganesh, K.N. (2010). Water
induced switching of β-structure to polyproline
II conformation in the 4S-aminoproline
polypeptide via H-bond rearrangement.
Organic Letters 12:5390-5393.
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Chemical Biology of Lipids and
Ion Channel Proteins
Jeet Kalia
Assistant Professor
Wellcome Trust/DBT India
Alliance Intermediate Fellow
(from March 2015)
[email protected]
Jeet Kalia received his bachelors and masters
Research in the Kalia laboratory is intrinsically
sensation and chemical sensing. Our group is
interdisciplinary and lies at the interface of
developing small molecule modulators of TRP
chemistry and biology. We utilize diverse tools
and voltage-activated channels. In addition
ranging from synthetic chemistry and
to utilizing these compounds as candidates
molecular biology to electrophysiology and
for drug development, we study the detailed
protein chemistry to address problems in ion
mechanism of action of these compounds on
channel biology, lipid biology, and
their target ion channels by utilizing
bioconjugation.
electrophysiological techniques, providing
A major thrust area of the group is the
development of activity-based probes and
small molecule modulators of ion channel
insights into the mechanism of opening and
closing of these fascinating molecular
machines.
proteins that could ultimately have
Another major focus of the laboratory is
Kharagpur, India. He obtained his PhD in
therapeutic applications and serve as
developing chemical biology-based
Biochemistry in 2008 from the University of
mechanistic probes. Ion channels are
approaches to study lipids. There are
membrane proteins expressed in all cell types
thousands of lipids in cells, most with
and are extremely important for life. For
undefined function. One reason why lipids
example, voltage-activated potassium and
remain poorly understood as compared to
sodium channels expressed in neurons
proteins and nucleic acids is that powerful
underlie the action potential which
tools available to study them in cells are
constitutes the nerve impulse. Other ion
lacking. We aim to address this urgent unmet
channels such as TRP channels are involved in
need by developing new technologies to
education at Indian Institute of Technology (IIT)
Wisconsin–Madison, where he worked in the
laboratory of Prof. Ronald Raines. There, he
performed chemical biology research focused
primarily on bioconjugation. He then moved to the
laboratory of Dr. Kenton Swartz as a National
Institute of Neurological Disorders and Stroke
(NINDS) competitive postdoctoral fellow at the
National Institutes of Health (NIH) where his research
focused on ion channel biology.
a multitude of processes including thermal
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label lipids in cells with synthetic, tailor made
chemical handles, thereby endowing them
with desired properties. These approaches
will be applied to elucidate facets of lipid
and membrane biology, including
understanding the role of lipids in ion
channel function.
Multidisciplinary approach of the
laboratory
Our third major interest is in developing novel
methods of bioconjugation—a term that
refers to the chemical derivatization of
biomolecules. Site specific bioconjugation
techniques facilitate a host of applications,
including protein labeling with affinity tags
and fluorophores, development of protein
Ion channel physiology and
biophysics
Kalia, J., Milescu, M., Salvatierra, J., Wagner,
J., Klint, J.K., King, G. F., Olivera, B.M. and
Bosmans, F. (2015). From foe to friend: Using
animal toxins to investigate ion channel
function. Journal of Molecular Biology
427:158-175.
Gilchrist, J., Dutton, S., Diaz-Bustamante, M.,
McPherson, A., Olivares, N., Kalia J., Escayg,
A. and Bosmans, F. (2014). Nav1.1
modulation by a novel triazole compound
attenuates epileptic seizures in rodents. ACS
Chemical Biology 9:1204-1212.
based therapeutics, and protein
Marshall, C., Agarwal, N., Kalia, J., Grosskopf,
immobilization. We are interested in
V., McGrath, N., Abbott, N.L., Raines, R.T.
developing synthetic organic compounds
and Shusta, E.V. (2013). Facile chemical
and ligation methods for site-specific protein
functionalization of proteins through intein-
bioconjugation.
linked yeast display. Bioconjugate Chemistry
24:1634-1644.
Kalia, J. and Swartz, K.J. (2013). Common
principles of voltage-dependent gating for
Hv and Kv channels. Neuron 77:214-216.
Kalia, J. and Swartz, K.J. (2011). Elucidating
the mechanism of action of a classical drug:
Guanidine compounds as inhibitors of
Elucidating roles of lipids
voltage-gated potassium channels.
Molecular Pharmacology 80:1085-1095.
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Structural Biology
Saikrishnan Kayarat
Assistant Professor
[email protected]
Saikrishnan Kayarat did his BSc in Physics at
Fundamental cellular processes rely on
activities of the R-M enzymes is not well
protein machines that use energy to perform
understood. Using X-ray crystallography and
specific tasks. Often, this involves
other tools of structural biology, a molecular
orchestration of activities of various
framework for the function and regulation of
functional domains of the protein molecule.
NTP-dependent R-M enzymes will be
The principal aim of my research is to gain
elucidated. The findings of the project will
insights into the working of such complex
help unravel how the enzymes perform and
protein molecules by studying their structure
coordinate their varied activities, and will also
in atomic detail.
facilitate the understanding of how other
One of the model systems chosen for this
study is nucleoside triphosphate (NTP)
University College, Thiruvananthapuram
dependent restriction-modification (R-M)
followed by Integrated PhD in Biological
enzymes. In general, these enzymes bind to
Sciences from the Indian Institute of Science,
Bangalore, India. Subsequent to postdoctoral
work at Cancer Research, UK, he joined IISER
Pune as a Wellcome Trust-DBT Intermediate
Fellow in 2010.
complex protein machines involved in
nucleic acid transactions work.
a specific DNA sequence, perform
sequence-specific methylation
(modification), translocate DNA by hydrolysis
of NTP and nucleolytically cleave it
(restriction). Modification of host DNA
protects it from restriction, while unmodified
foreign DNA (eg. bacteriophage DNA) is
cleaved. The molecular basis of this
fascinating interplay and regulation of
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Saikrishnan, K., Yeeles, J.T., Gilhooly, N.S.,
Krajewski, W.W., Dillingham, M.S. and Wigley,
D.B. (2012). Insight into Chi recognition from
the structure of AddAB-type helicase–
nuclease complex. EMBO Journal 31:15681578.
Saikrishnan, K., Powell, B., Cook, N.J., Webb,
M.R. and Wigley, D.B. (2009). Mechanistic
basis of 5’-3’ translocation by SF1B helicases.
Cell 137:849-859.
Saikrishnan, K. Griffiths, S.P., Cook, N., Court,
R. and Wigley, D.B. (2008). DNA binding to
RecD: role of the 1B domain in SF1B helicase
activity. EMBO Journal 27:2222-2229.
Saikrishnan, K., Kalapala, S.K., Varshney, U.
and Vijayan, M. (2005). X-ray structural
studies of Mycobacterium tuberculosis RRF
and a comparative study of RRFs of known
structure. Molecular plasticity and biological
implications. Journal of Molecular Biology
345:29-38.
Top panel: A proposed model for restriction by a class of NTP-dependent R-M enzymes; Bottom panel:
Domain architecture of a minimal R-M enzyme bound to target sequence
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Structure and Mechanism of
Cytoskeletal Motility Systems
Cell motility is a fundamental process in
motility, thus capturing the assemblies at both
biology. In many organisms, movement is
spatial and temporal resolutions.
mediated by appendages like cilia, flagella
and pili. In addition, motility is also driven by
Gayathri Pananghat
INSPIRE Faculty Fellow
[email protected]
the dynamics of assembly of cytoskeletal
filaments, as in eukaryotic cell crawling.
Research in bacterial cell biology has
identified a few novel modes of motility
based on the bacterial cytoskeleton. My
research focus is to understand the molecular
mechanism of motility using these as model
Gayathri Pananghat did her Integrated MSc
in Chemistry and Biological Sciences from Birla
Institute of Technology and Science, Pilani,
and PhD from the Indian Institute of Science,
Bangalore. After a brief stint at IISER Pune as
visiting faculty, she worked at MRC Laboratory
of Molecular Biology, Cambridge, UK for her
postdoctoral research. She joined IISER Pune
as INSPIRE Faculty from April 2013.
systems.
A long-term objective of the research is to
compare and contrast different systems of
motility based on their molecular mechanism
and bring out unifying features between
bacterial and eukaryotic cell motility, thus
understanding the basic principles of cell
motility. The fundamental nature of the
research has potential to establish significant
links in the evolution of cytoskeletal systems
across the different domains of life.
Cytoskeleton-based motility is an example of
how the dynamic assembly of
macromolecules, in response to
environmental cues, leads to movement. I
plan to use the techniques of structural
biology (mainly X-ray crystallography and
cryoelectron microscopy) and singlemolecule fluorescence microscopy to study
the structure and dynamics of assembly of
the macromolecular complexes involved in
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Gayathri, P.*, Fujii, T.*, Namba, K., Löwe, J.
(2013). Structure of the ParM filament at 8.5 Å
resolution. Journal of Structural Biology
184:33-42. [* Equal authors]
Gayathri, P., Fujii, T., Møller-Jensen, J., van
den Ent, F., Namba, K. and Löwe, J. (2012). A
bipolar spindle of antiparallel ParM filaments
drives bacterial plasmid segregation.
Science 338:1334-1337.
Gayathri, P., Sujay Subbayya I.N., Ashok, C.S.,
Selvi, T.S., Balaram, H. and Murthy, M.R.N.
(2008). Crystal structure of a chimera of
human and Plasmodium falciparum
hypoxanthine-guanine phosphoribosyl
transferases provides insights into
oligomerisation. Proteins 73:1010-1020.
Gayathri, P., Balaram, H. and Murthy, M.R.N.
(2007). Structural biology of plasmodial
proteins. Current Opinion in Structural Biology
17:744-754.
Gayathri, P., Satheshkumar, P.S., Prasad, K.,
Nair, S., Savithri, H.S. and Murthy, M.R.N.
100 nm
(2006). Crystal structure of the serine
Electron microscopy image of negatively-stained filaments of a bacterial cytoskeletal protein
(left); Crystal structure of a GTPase involved in positioning of bacterial motility complexes
(right)
protease domain of Sesbania mosaic virus
polyprotein. Virology 346:440-451.
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Mechanism of Membrane Fission
during Vesicular Transport
Thomas Pucadyil
Assistant Professor
[email protected]
Thomas Pucadyil received his PhD at the
Centre for Cellular and Molecular Biology,
Hyderabad, India. Subsequent to a
postdoctoral training at The Scripps Research
Institute, La Jolla, USA, he joined IISER Pune in
October 2010.
Cellular organelles such as the mitochondria,
Fission reactions occur under non-equilibrium
golgi apparatus, endosomes and
conditions inside the cell, often by the
multivesicular bodies are generated through
consumption of energy from nucleotide
highly coordinated vesicular trafficking
hydrolysis, and time-resolved approaches
processes. The creation of such membrane
are therefore necessary to unravel their
compartments is critically dependent on the
mechanistic details. For this, we use a
function of specialized protein machines that
bottom-up approach of reconstituting
act at topologically well-defined narrow
partial reaction en route to fission using novel
necks of transport intermediates during late
model membrane systems that mimic late
stages of vesicular trafficking events (see
stages of vesicular transport intermediates in
schematic) to accomplish an energetically
terms of membrane topology as well as lipid
unfavorable process of membrane fission
composition. The overall objective of our
leading to the release of nascent transport
research is to arrive at a mechanistic
vesicles. Conformational changes occurring
description of membrane fission reactions
in these protein machines are believed to be
with an obligatory focus on identifying novel
strongly coupled to the local application of
catalysts in cells and developing
forces on the lipid bilayer in order to bring
fluorescence-based experimental
bilayers close together for the spontaneous
approaches to better understand these
generation and stabilization of the
reactions.
hemifusion intermediate, which leads to a
breakage of the membrane.
22
Shnyrova et al. (2013). Geometric catalysis of
membrane fission driven by flexible dynamin
rings. Science 339:1433-1436.
Neumann et al. (2013). Analyzing membrane
remodeling and fission using supported
bilayers with excess membrane reservoir.
Nature Protocols 8:213-222.
Pucadyil TJ. (2011). Dynamic remodeling of
membranes catalyzed by dynamin. Current
Topics in Membranes 68:33-47.
Pucadyil and Schmid (2010). Supported
bilayers with excess membrane reservoir: a
template for reconstituting membrane
budding and fission. Biophysical Journal
99:517-25.
Pucadyil and Schmid (2009). Conserved
functions of membrane active GTPases in
coated vesicle formation. Science 325:12171220.
Pucadyil and Schmid (2008). Real-time
visualization of dynamin-catalyzed
membrane fission and vesicle release. Cell
Schematic showing the site of action of fission catalysts (left) and the proposed stages during a
135:1263-1275.
membrane fission reaction (right).
23
Design Principles of Proteins:
Structure, Function and Dynamics
Mrinalini Puranik
Associate Professor
[email protected]
Mrinalini Puranik has moved to IISER Pune from
the National Centre for Biological Sciences
(NCBS) Bangalore, India in 2012. She did her
doctoral work at the Indian Institute of
Science (IISc), Bangalore followed by
postdoctoral work at Princeton University, USA.
A majority of cellular processes do ultimately
We are using innovative approaches that
arise from protein-protein, protein-nucleic
combine spectroscopic, biochemical and
acid, and protein-lipid interactions.
computational strategies to understand the
Deconstructed to a molecular level, these
design principles of proteins with high spatial
interactions are governed by rates of
and temporal resolution. Proteins being
enzymatic catalysis and allosteric control of
studied in the lab are: protein-nucleic acid
access to interaction sites. Therefore a
complexes involved in purine metabolism,
strategy underlying drug design is
ATP homeostasis and DNA repair. These
modulation of the function of proteins. Eco-
fascinating proteins have the ability to
friendly industrial processes rely on our ability
catalyze many types of substrates. We aim
to develop enzymes designed for specific
to understand how catalytic efficiency and
chemical catalysis of small molecules. To
protein plasticity coexist. We are also
attain these goals it is critical to understand
measuring the dynamics of proteins relevant
the fundamental design principles of natural
to the chemical step of the catalysis.
proteins. Natural enzymes can achieve
turnover rates of 1018 while designed
enzymes rarely achieve 1% of this rate.
Clearly, we still do not have sufficient
understanding to modulate desired
properties with the required specificity for
target proteins. Particularly less understood is
the role of protein dynamics in governing
function.
24
Gogia, S., Balaram, H. and Puranik, M.
(2011). HGPRT distorts the purine ring of
nucleotide substrates and perturbs pKa of
bound xanthosine monophosphate.
Biochemistry 50:4184.
Jayanth, N. and Puranik, M. (2011).
Methylation stabilizes the imino tautomer of
dAMP and amino tautomer of dCMP in
solution. Journal of Physical Chemistry B
115:6234.
Shanmugasundaram, M. and Puranik, M.
(2011). Vibrational markers of structural
distortion in adenine nucleobases upon
DNA damage. Physical Chemistry and
Chemical Physics 13:3851-3862.
Gogia, S., Jain, A. and Puranik, M. (2009).
Structures, ionization equilibria and
tautomerism of 6-oxopurines in solution.
Journal of Physical Chemistry B 113:1510115118.
Left: Structure of human HGPRT with bound substrate (guanine monophosphate (1HMP);
Right: Raman Lab showing the Ti-S based tunable deep UV excitation source
25
Role of Lipids in the Evolution of Life
Sudha Rajamani
Assistant Professor
[email protected]
Sudha Rajamani obtained her PhD in
Biochemistry in 2002 from National Institute of
Immunology, New Delhi, India. She was a
postdoctoral fellow at FAS Center for Systems
Biology at Harvard (Cambridge, USA) and at
University of California (Santa Cruz, USA)
before joining IISER Pune in February 2012.
The fundamental question of how life
hallmark of non-enzymatic replication
originated is one of the greatest scientific
mechanisms? In this context, we are
mysteries. In particular, the processes by
particularly interested in delineating the
which polymers capable of catalysis and
catalytic role of amphipihiles on
replication emerged and propagated on
nonenzymatic polymerization reactions since
early Earth are still elusive. Plausible prebiotic
amphiphilic boundary structures are
mechanisms have been described that result
believed to have been crucial in setting the
in biologically important monomers. These
stage for emergence and evolution of
are required to synthesize complicated
encapsulated life. We use phospholipids and
molecules like nucleic acids and peptides.
mixed fatty acid-based lipids as model
However, it is still unclear what relevant
membrane systems. The physical and
processes might have enabled the formation
chemical properties, specifically that of fatty
of complex mixtures of such oligomers.
acid based membranes, make them an
Therefore, an important question we hope to
excellent candidate for components of
answer is: what plausible processes allow
protocells. These studies will also help discern
efficient oligomer synthesis to occur under
the mechanistic details of how individual
prebiotic conditions that result in
components of a putative protocell interact,
informational molecules capable of catalytic
which we hope will contribute towards what
activity? Subsequently, how did these
might be a reality soon; to evolve synthetic
functional sequences replicate their
life in the lab using a bottom-up approach.
information efficiently even in the face of
high intrinsic mutation rates, which is a
26
Mungi, C. V. and Rajamani. S. (2015).
Characterization of RNA-like oligomers from
lipid-assisted nonenzymatic synthesis:
Implications for origin of informational
molecules on early earth. Life 5(1):65-84.
Derr, J., Manapat, M.L., Rajamani, S., Leu, K.,
Xulvi-Brunet, R., Joseph, I., Nowak, M.A. and
Chen, I.A. (2012). Prebiotically plausible
mechanisms increase compositional diversity
of nucleic acid sequences. Nucleic Acids
Research 40(10):4711-4722..
Leu, K., Obermayer, B., Rajamani, S.,
Gerland, U. and Chen, I.A. (2011). The
prebiotic evolutionary advantage of
transferring genetic information from RNA to
DNA. Nucleic Acids Research 39:8135-8147.
Rajamani, S., Ichida, J.K., Antal, T., Treco,
D.A., Leu, K., Nowak, M.A., Szostak, J.W. and
Chen, I.A. (2010). Effect of stalling after
mismatches on the error catastrophe in nonenzymatic nucleic acid replication. Journal
of the American Chemical Society 132:58805885.
Top panel: Formation of higher order structures from amphiphiles
Bottom panel: Lipid-assisted synthesis of oligomers
27
Image: Rikhy Lab
28
Cell & Developmental Biology
Nagaraj Balasubramanian
Mayurika Lahiri
Girish Ratnaparkhi
Richa Rikhy
L.S. Shashidhara
29
Cell Adhesion and Trafficking
Nagaraj
Balasubramanian
Assistant Professor
Alliance Senior Fellow
[email protected]
Most cells in the human body depend on their
membrane raft microdomains to control
ability to attach to the extracellular matrix (a
anchorage dependent Erk, Akt and Rac
network of secreted proteins coating tissue
signaling. Upon loss of adhesion membrane rafts
and blood vessels) to grow, survive and
are rapidly endocytosed from the plasma
migrate. Signaling pathways controlling these
membrane to switch off this signaling. Re-
functions are regulated by integrin mediated
adhesion returns membrane rafts to the plasma
adhesion to these matrix proteins to confer
membrane to restore signaling. Regulators of
anchorage dependence. Cancer cells
this pathway could hence regulate anchorage
overcome this regulatory control to become
dependence in cells.
anchorage independent and acquire their
unique growth and survival advantage. This
Nagaraj Balasubramanian did his BSc and
coupled with their ability to migrate and
MSc in Microbiology from the University of
undergo metastasis contributes to cancer
Bombay and PhD in Biochemistry from the
mortality. Understanding how adhesion
Cancer Research Institute, Tata Memorial
regulates growth, survival, migratory signals
Center, India. He did his postdoc at the
University of Miami and then at University of
Virginia, USA. He was a Research Assistant
Professor at the University of Virginia before
joining IISER Pune as a Ramalingaswami Fellow
in 2010.
and how transformed cells overcome this
regulation, is important to our knowledge of
how cancers are caused and eventually
treated.
We have shown this endocytosis to be
regulated through caveolae, dependent on
Caveolin-1 and its phosphorylation at the
tyrosine-14 residue (pY14Cav1) and its
exocytosis to be regulated by Arf6 and RalA as
part of the exocyst complex. Adhesion
regulates the activation of these GTPases to
regulate this pawthway. RalA and RalB are
differentially regulated by adhesion, something
we are actively trying to understand in the lab.
Integrin mediated adhesion regulates the
Cancer cells deregulate this trafficking pathway
trafficking and plasma membrane localization
by (a) losing caveolin-1 (a tumor suppressor) (b)
of cholesterol and sphingolipid enriched
and/or activating Arf6 and RalA (tumor
30
promoters) to promote anchorage
M.* (2012). Dextran vesicular carriers for dual
independent membrane raft targeting and
encapsulation of hydrophilic and hydrophobic
signaling.
molecules and delivery in
Understanding how adhesion regulates
caveolar endocytosis and RalA-exocyst
Balasubramanian, N.,* Meier, J.A., Scott, D.W.,
function to elucidate their combined
Norambuena, A., White, M.A. and Schwartz,
significance in anchorage dependence and
M.A. (2010). The RalA-exocyst complex
cancer cell transformation is the ongoing
regulates integrin-dependent membrane raft
focus of my lab. Also of interest to the lab is
exocytosis and growth signaling. Current
elucidating the crosstalk between these
Biology 20:75–79.
regulators and its significance to this and other
cellular functions. We also study how these
trafficking pathways and the signaling process
they regulate are differentially regulated in 3D
microenvironments.
We are also interested in testing new
stratergies for targeting Ral and Arf6 in
cancers and have tested novel selfassembling
nanovesicle drug delivery systems in cancers.
GM1 containing membrane rafts labeled
with Cholera toxin B (Red) and
endocytosed in suspended tubulin-GFP
expressing fibroblasts localize in vesicles
exocytosed on microtubule strands when
re-adherent on fibronectin.
cells. Biomacromolecules 13(11):3627-3640.
Balasubramanian, N., Scott, D.W., Castle, J.D.,
Casanova, J.E. and Schwartz, M.A. (2007). Arf6
and microtubules in adhesion-dependent
trafficking of lipid rafts. Nature Cell Biology
9:1381-1391.
Gaus, K., Le Lay, S., Balasubramanian, N. and
Schwartz, M.A. (2006). Integrin-mediated
adhesion regulates membrane order. Journal
of Cell Biology 174:725-734 (Highlight –In this
issue).
Pramod, P.S.#, Shah, R.#, Chapekar, S.
del Pozo, M.N., Balasubramanian, N., Alderson,
Balasubramanian, N.* and Jayakannan, M.*
N.B., Kiosses, W.B., Grande-Garcia, A.,
(2014). Polysaccharide nano-vesicular
Anderson, R.G.W. and Schwartz, M.A. (2005).
multidrug carrier for synergistic killing of cancer
Phospho-caveolin-1 mediates integrin-
cells. Nanoscale 6(20):11841-55.
regulated membrane domain internalization.
Pramod, P., Takamura, K., Chaphekar,
S., Balasubramanian, N.* and Jayakannan,
Nature Cell Biology 7:901-908.
31
Genomic Integrity and DNA Damage
Mayurika Lahiri
Assistant Professor
[email protected]
The research in my lab focuses on the use of
transformed acini were observed to contain
biochemical and molecular techniques in
fewer nuclei without appreciable change in
human cell culture systems to better
volume of acini compared to non-treated cells.
understand the DNA damage response
Interestingly, morphometry analysis of each
mechanisms of cells to maintain genome
nuclei in the transformed acini revealed an
stability. Damage response mechanisms
increase in volume and surface area
include cell cycle checkpoint arrest, DNA
compared to control acini. Currently, the non-
repair and apoptosis. Understanding the key
tumorigenic cells are being modified to have
processes involved in the maintenance of
an altered expression of key genes, which are
genomic integrity is critical in the prevention,
known or speculated to play a vital role in the
diagnosis and treatment of a number of human
process of breast carcinogenesis with attempt
pathologies, including cancer.
to dissect out the molecular mechanisms
Mayurika Lahiri did her PhD from University of
Wolverhampton, UK. She spent her
One avenue that the lab is currently engaged
postdoctoral years first at Tufts University, USA
in studying is the effect of alkylating agents on
and then at MGH Cancer Center, Harvard
Medical School, USA. She joined IISER Pune in
2008.
morphogenesis of non-tumorigenic breast
involved in the process of tumorigenesis
initiated by the absence or presence of such
genes.
epithelial cells using 3D culture systems. Loss of
Another avenue that my lab is working on is the
cellular architecture and polarity of breast
characterization of the interaction between
tissue is one of the early markers for onset of
checkpoint protein, TopBP1 and mismatch
breast cancer. Addition of alkylating agents to
repair protein complex, Msh2-Msh6 as well as
non-transformed epithelial cells grown as 3D
an anti-apoptotic protein, Api5 following DNA
cultures caused disruption of apico-basal
damage. Both Msh2-Msh6 and Api5 were
polarity as well as upregulation of vimentin thus
observed to interact physically with TopBP1.
denoting a transformed phenotype. The
32
Currently, the functional relevance of the
interaction is being investigated.
Jain, D.R., Anandi, V.L., Lahiri, M. and
We are also investigating the molecular
Ganesh, K.N. (2014). Influence of pendant
mechanism by which platelet activating factor,
chiral C(γ)-(alkylideneamino/guanidino)
PAF is able to induce transformation of non-
cationic side-chains of PNA backbone on
tumorigenic breast epithelial cells grown as
hybridization with complementary DNA/RNA
spheroids as well as promote migration of
and cell permeability. Journal of Organic
metastatic breast cancer cells.
Chemistry 79 (20):9567-9577. doi: 10.1021/jo501639m.
Bodakuntla, S., Anandi, V.L., Sural, S., Trivedi,
A
P. and Lahiri, M. (2014). N-nitroso-N-ethylurea
activates DNA damage surveillance
pathways and induces transformation in
mammalian cells. BMC Cancer 14(1): 287.
doi:10.1186/1471-2407-14-287.
Kar, M., Tiwari, N., Tiwari., M., Lahiri, M.* and
B
C
Sen Gupta, S.* (2013). Poly-L-Arginine grafted
silica mesoporous nanoparticles for
enhanced cellular uptake and their
application in DNA delivery and controlled
drug release. Particle & Particle Systems
Characterization 30:166-179. * corresponding
authors
Liu, S*., Shiotani, B*., Lahiri, M., Marechal, A.,
NEU induces upregulation of vimentin and disrupts polarity in MCF10A breast acini. MCF10A cells
were grown as 3D ‘on top’ cultures in Matrigel™. 2 mM NEU was administered on Day 0 and Day 2.
The acini were cultured for 20 days and then immunostained for (A) α6-integrin (green), β-catenin
(red) and DAPI (blue) to stain nuclei (B) Vimentin (green) a marker for EMT and (C) E-cadherin
(green). The data is representative of 40 – 50 acini from three biologically independent experiments.
Tse, A., Leung, C., Glover, J. N. M., Yang, X.
and Zou, L. (2011). ATR phosphorylation as a
molecular switch for checkpoint activation.
Molecular Cell 43:192-202. *equal
contribution
33
Universal Mechanisms in
Animal Development
Girish Ratnaparkhi
Associate Professor
[email protected]
Girish Ratnaparkhi received his PhD in
Molecular Biophysics at the Indian Institute of
Science (IISc), Bangalore, India. He had
Animals as different as humans, worms, and
Lineage-specific gene family expansion (LSE)
flies use remarkably similar molecular
appears to be an important source of
mechanisms to control their development.
structural and regulatory diversity in
Discoveries of developmental paradigms in
eukaryotes during evolution. We are studying
one organism have provided insights into
LSE in the Drosophila MADF-BESS family of
development processes of other organisms.
proteins with a focus on understanding roles
My group utilizes Drosophila melanogaster
and Hydra magnipapillata as model
Amyotrophic lateral sclerosis (ALS) is a
principles underlying animal development
progressive, neurodegenerative disease
and disease.
characterized by loss of motor neurons;
In Drosophila, we are studying the role of the
small ubiquitin like modifier SUMO, a posttranslational modifier, in regulating gene
Biological Sciences (NCBS), Bangalore, India
expression in the innate immune system using
Department at the University of California at
Los Angeles, USA. He joined IISER Pune in 2008.
regulation in pattern formation.
organisms to study common molecular
postdoctoral stints at the National Centre for
as also in the Chemistry and Biochemistry
for this interesting family in transcriptional
a proteomics based discovery process in
combination with genetics. Currently we are
uncovering mechanistic roles for the SUMO
targets uncovered in our screen. In Hydra,
we are interested in roles for SUMOylation in
stress, immunity, and regeneration.
leading to gradual paralysis and death of
the patient. VAPB/ ALS8 is one locus in
humans where mutation can cause ALS. We
have conducted a large genetics screen in
Drosophila to identified pathways and
molecules that interact with Drosophila VAPB
and may therefore contribute to disease
pathogenesis. We find that multiple ALS loci
are connected in a gene network that may
malfunction in the disease condition.
34
SELECTED PUBLLICATIONS
Shukla, V.S., Habib, F., Kulkarni, A. and
Ratnaparkhi, G.S. (2014). Gene duplication,
lineage-specific expansion, and
subfunctionalization in the MADF-BESS family
patterns the Drosophila wing hinge. Genetics
196:481-496.
Ratnaparkhi, G.S. and Courey, A.J. (2014).
Cascades, gradients and gene-networks in
dorsoventral patterning. In: Principles of
Developmental Genetics Moody, S (Ed.),
Elsevier Publishing.
Senthilkumar, D., Verma, H.K., Ueda, R.,
Ratnaparkhi, A. and Ratnaparkhi, G.S. (2014).
A genetic screen identifies Tor as an
interactor of VAPB in a Drosophila model of
Amyotrophic Lateral Sclerosis. Biology Open
3:1127-1138.
A. LPS induced SUMO proteome in Drosophila S2 cells mapped onto the Drosophila Interactome;
displayed using Cytoscape.
Khan, U., Mehere, P., Senthilkumar D. and
B. Transgenic Hydra expressing 6XHis:FLAG-Hydra-SUMO:GFP in mosaic (blue) patches; driven by
Ratnaparkhi, G.S. (2013). The Hydra small
the Hydra Actin promoter.
ubiquitin-like modifier. Genesis: Journal of
C. A phylogenetic tree depicting relationships between MADF-BESS domain proteins in Dipterans.
Genetics & Development 51:619-629.
D. Patterning of the Dorsal-Venral axis in the embryo by opposing gradients of Dorsal (DL) and
Decapentaplegic (Dpp). DL is SUMOylated at K382.
E. Dendritic arborizatiion by Type IV Da neurons in Drosophila larvae. GFP is driven by
promoter/enhancer elements of the pickpocket (ppk) gene.
F. The larval neuromuscular junction. Horseradish peroxidase (HRP, red) marks neurons while green
marks Discslarge (Dlg), a postsynaptic protein located in the sub-synaptic reticulum.
35
Cell and Developmental Biology
Richa Rikhy
Higher animals are composed of individual
formation of polarised plasma membrane
cell types, which are specialized to perform
architecture in epithelial cells and its
different functions such as nutrient uptake,
morphogenesis with the use of high-
secretion, sensory perception, contraction,
resolution microscopy in various genetic
and reproduction. These cells have highly
backgrounds.
specialized morphologies to achieve their
Assistant Professor
function. They form during development by
different cues that determine tissue types to
make an adult organism. We are interested
[email protected]
in understanding how these cell
morphologies arise and are determined
Richa Rikhy did a BSc in Life Sciences and
Biochemistry from St Xavier’s College, Mumbai
University followed by a Masters in
Biochemistry at Maharaja Sayajirao University,
Baroda and a PhD with K S Krishnan at the
Tata Institute of Fundamental Research,
Mumbai, India. She continued her
postdoctoral fellowship with Jennifer
Lippincott Schwartz at the National Institutes
of Health, Bethesda, USA and has joined as a
faculty with IISER Pune in August 2010.
.
during organism development.
Our studies have found the presence of celllike compartments in the absence of plasma
membrane boundaries in the syncytial
Drosophila embryo. The continuous plasma
membrane is polarised with microvilli at the
apical surface and a lateral domain
containing junctional proteins. This is
The first morphologically distinct cell type to
maintained by the cytoskeleton and is likely
form during embryo development is an
to be important for the restriction of
epithelial cell. It has an apical and a
morphogen gradients, which set the body
basolateral plasma membrane separated by
axes in the developing embryo. Our studies
junctional barriers. This epithelial layer is
are presently focused towards
transformed to give rise to other cell types
understanding the molecular mechanisms of
and different tissues. The transparent
cellular architecture formation and its
Drosophila embryo is an excellent model to
relationship with developmental axes
understand the mechanisms used in the
formation.
36
We have also found polarized distribution of
mitochondria in epithelial cell types during
oogenesis and embryogenesis. We are
studying the role of distinct mitochondrial
morphology on cell signaling and
differentiation during Drosophila oogenesis
and embryogenesis.
Rikhy, R., Mavrakis, M. and LippincottSchwartz, J. (2015). Dynamin function is
essential for metaphase furrow formation
and compartmentalization in the syncytial
Drosophila embryo, Biology Open (in press).
Mitra, K.*, Rikhy, R.*, Lilly, M. and LippincottSchwartz, J. (2012). Mitochondria regulate
signaling events underlying cell
differentiation in the follicle cell layer during
Drosophila oogenesis Journal of Cell Biology
197 (4):487-497. *equal contribution
Sherlekar, A. and Rikhy, R. (2012). Syncytial
cellular architecture and gradient dynamics,
is there a correlation? Frontiers in Cell Biology
7(1):73-82.
Daniels, B., Rikhy, R., Renz, M., Dobrowsky, T.
and Lippincott-Schwartz, J. (2012). Multiscale
diffusion in mitotic Drosophila syncytial
blastoderm. Proceedings of the National
Academy of Sciences USA 109(22):85888593.
Mavrakis, M., Rikhy, R. and Lippincott-
A. The cellular architecture in the syncytial Drosophila embryo. The plasma membrane is
polarized with microvilli on the surface and junctional proteins in the lateral membrane. B.
Surface view of Drosophila embryos comprises a polygonal organization of pseudo cells in
interphase and metaphase. Sagittal views show a greater membrane ingression in
metaphase. C. Mitochondrial morphology varies in different cell types in oogenesis.
Schwartz, J. (2009). Plasma membrane
polarity and compartmentalization are
established prior to cellularization in the fly
embryo. Developmental Cell 16(1):93-104.
37
Genetics and Evolutionary
Developmental Biology
Research in our laboratory aims to understand
this seminal work Ed Lewis was awarded the
developmental mechanisms that determine
Nobel Prize in 1995).
physical position, size and shape of various
cells/tissues/organs in our body. Our
L.S. Shashidhara
Professor and Chair, Biology
[email protected]
experimental model system is the
development of flight appendages in the
fruitfly Drosophila melanogaster. At the
molecular level, insect-wing developmental
pathway is conserved and is similar to limb
development in vertebrates including human.
L S Shashidhara obtained his BSc and MSc
(Genetics and Plant Breeding) in 1987 at the
University of Agricultural Sciences, Dharwad,
India; and PhD (Molecular Genetics) in 1991
from the University of Cambridge, UK. After
postdoctoral work at the University of
Cambridge, UK and at the National Centre for
Biological Sciences, Bangalore, India,
Shashidhara joined the Centre for Cellular and
Ubx modulates activities of certain key
signaling pathways such as Wg/Wnt, TGF-β
and Egfr/Ras pathways to suppress wing
development and specify haltere
development. Our work has opened up many
avenues to study genetic mechanisms and to
identify novel components that help in fine-
While most insects have four wings (all directly
tuning these pathways, which are implicated
contribute to the flight), flies such as Drosophila
in many cancers. Our current work involves
have only one pair of wings. In these insects,
comparative genomic analyses to identify
only the forewings perform the flight function
those genetic elements that are subjected to
and the hind-wings are modified as small club-
evolutionary changes causing differences in
shaped balancing organs called haltere.
wing number, shape and size amongst various
Specification of haltere by the transcription
factor Ultrabithorax (Ubx: a member of Hox
Molecular Biology (CCMB), Hyderabad, India
family of genes) in Drosophila is the first
as a scientist in 1995 and moved to IISER Pune
example for the genetic control of the
in August 2007.
Several observations from our lab suggest that
specification of body plan in any animal (for
insect groups such as Apis, butterflies, silkworm,
Tribolium, mosquito, and Drosophila.
38
De Graeve, F.M., Van de Bor, V., Ghiglione, C.,
Cerezo, D., Jouandin, P., Ueda, R., Shashidhara,
L.S. and Noselli, S. (2012). Drosophila apc
regulates delamination of invasive epithelial
clusters. Developmental Biology 368:76-85.
Agrawal, P., Habib, F., Yelagandula, R. and
Shashidhara, L.S. (2011). Genome-level
identification of targets of Hox protein
Ultrabithorax in Drosophila: Novel mechanisms for
target selection. Scientific Reports 1:205.
Usha, N. and Shashidhara, L.S. (2010). Interaction
between Ataxin-2 Binding Protein 1 and Cubitusinterruptus during wing development in
Drosophila. Developmental Biology 341:389-399.
Berger, C., Kannan, R., Myneni, S., Renner, S.,
Shashidhara, L.S. and Technau, G.M. (2010). Cell
cycle independent role of Cyclin E during neural
cell fate specification in Drosophila is mediated
by its regulation of Prospero function.
Developmental Biology 337:415-424.
Kannan, R., Berger, C., Myneni, S., Technau,
G.M. and Shashidhara, L.S. (2010). Abdominal-A
mediated repression of Cyclin E expression
Evolution of two-winged flies from four-winged ancestral species is an intriguing
phenomenon which is being explored at a molecular level at IISER Pune.
during cell-fate specification in the Drosophila
central nervous system. Mechanisms of
Development 127:137-145.
39
Photo: Barua Lab
40
Ecology, Evolution & Biodiversity
Ramana Athreya
Deepak Barua
Sutirth Dey
Milind Watve
2013-14
41
Biological Diversity:
Research and Conservation
I am interested in research on and conservation
of the rich biological diversity in India with specia
focus on Arunachal Pradesh. I initiated and lead
the Eaglenest Biodiversity Project, which is
Ramana Athreya
Associate Professor
[email protected]
inventorying the fauna of Eaglenest sanctuary in
Arunachal Pradesh and helping in its
conservation in partnership with the Bugun tribe
of that area. My research in this field involves
delineating the geographical distribution of
diversity across Arunachal and investigating the
factors responsible for the same. This work has
Ramana Athreya obtained PhD from the National
resulted in the discovery of several new taxa
Centre for Radio Astrophysics (TIFR), Pune, India in
including a spectacular bird species new to
1996. Following postdoctoral fellowships at the
Institute of Astrophysics, Paris (1998) and the
science.
European Southern Observatory, Chile (1999), and a
faculty position at NCRA, Pune (2003), he joined
IISER Pune in 2009. He is a Trustee of two
conservation NGOs: Kaati Trust (Pune) and EcoSystems India (Guwahati), and a member of the
Arunachal Pradesh State Wildlife Advisory Board. He
received the Whitley Award for Conservation from
the Whitley Fund for Nature (UK) in May 2011.
42
Agarwal, I., Mistry, V.K. and Athreya, R. (2010).
A preliminary checklist of the reptiles of
Eaglenest wildlife sanctuary, West Kameng,
Arunachal Pradesh, India. Russian Journal of
Herpetology 17:81-93.
Athreya, R.M. (2006). Conservation resources
for Eaglenest wildlife sanctuary. Kaati Trust,
Pune.
Athreya, R. (2006). A new species of Liocichla
(Aves: Timaliidae) from Eaglenest Wildlife
Sanctuary, Arunachal Pradesh, India. Indian
Birds 2:82–94.
43
Plant Physiological Ecology
Deepak Barua
Assistant Professor
[email protected]
There is tremendous diversity in plant responses to
India. Another aspect of this work is primarily
the environment and in the underlying traits and
conducted in the greenhouse/growth
mechanisms. Broad goals of my research are to
chambers which allows us greater control on
characterize such variation, identify traits and
the conditions used to grow, manipulate and
interactions among traits that translate to
asses plant performance. Here we are trying
variation in plant performance, and test how
to understand the mechanistic basis of
variation in performance influences population
variation in leaf and stem functional traits, the
persistence and adaptation in complex
integration between leaf and stem traits, and
ecological environments.
the consequences of the same for plant
Using an integrated approach, utilizing tools and
Deepak Barua completed his PhD in Biology
perspectives from evolutionary biology, ecology,
performance under different environmental
conditions.
physiology, biochemistry and molecular biology,
Other work in the lab investigates patterns in
work in my lab examines the adaptive
plant phenology – the timing of
significance of variation in plant functional traits.
developmental transitions - e.g., flowering,
Postdoctoral Fellow at the University of Toledo,
This includes work that investigates variation in
fruiting. This includes examining proximate
USA and Harvard University, USA before joining
leaf traits in woody tree species, the relationship
environmental cues and the underlying
of this variation to the environment, and the
endogenous mechanisms, and the ultimate
functional consequences of this variation. This
consequences of variation in phenology.
work is being carried out in various sites in
Work done by graduate students in the lab is
peninsular India, including the Northern Western
often independent of the major focus of my
Ghats, the Southern Western Ghats, and Central
research and include varied research
from Syracuse University, USA in 2003. He
worked as a Visiting Research Scholar at the
University of Potsdam, Germany and as a
IISER Pune in 2008.
44
questions including: thermotolerance in
tropical trees; plant-pollinator interactions;
evolution of plant sexual systems; and,
emphemeral plant communities in lateretic
plateaus.
Chiang, G.C.K., Barua, D., Dittmar, E., Kramer, E.M.,
Rubio de Casas, R. and Donohue, K. (2013).
Pleiotropy in the wild: the dormancy gene DOG1
exerts cascading control over life cycles. Evolution
67(3):883-893.
Barua, D., Butler, C.M., Tisdale, T.E. and Donohue, K.
(2012). Natural variation in germination responses to
seasonal cues and their associated physiological
mechanisms. Annals of Botany 109(1): 209-226.
Chiang, G.C.K., Barua, D., Kramer, E.M., Amasino,
R.M. and Donohue, K. (2009). The major flowering
time gene, Flowering Locus C, regulates germination
in Arabidopsis thaliana. Proceedings of the National
Academy of Sciences, USA 106:11661-11666.
Barua, D., Heckathorn, S.A. and Coleman, J.S.
(2008). Variation in heat-shock proteins and
photosynthetic thermotolerance in natural
populations of Chenopodium album from
contrasting thermal environments. Journal of
Integrative Plant Biology 50:1440-1451.
Barua, D. and Heckathorn, S.A. (2006). Heat-shock
protein accumulation in Solidago altissima in the
field and laboratory: interactive effects of light and
temperature. American Journal of Botany 93: 102109
45
Population Biology
Sutirth Dey
Associate Professor
[email protected]
I study the factors that determine how population
population, such that its stability properties
sizes change over time and space, using a
can be altered? What are the various factors
combination of mathematical modeling and
that are expected to play a role in
laboratory experiments. I also plan to investigate
determining the dynamics of fragmented
the various micro-evolutionary forces that impact
populations under perturbation? Questions
the genetic architecture of laboratory
like these have prompted us to launch a
populations. Current research themes in the lab
series of experiments aimed at investigating
include:
the effects of perturbations in spatially
Effects of localized perturbations on fragmented
populations: Due to its practical implications,
Sutirth Dey obtained PhD from Jawaharlal
Nehru Centre for Advanced Scientific
stabilizing fragmented populations is a major
area of research in conservation biology.
Research (JNCASR), Bangalore, India in 2007
Theoretical studies predict that localized
and joined IISER Pune as an Assistant Professor.
perturbations (i.e. adding or killing some
His non-academic interests include dramatics
and movies.
structured and unstructured populations.
Currently, Council of Scientific and Industrial
Research (CSIR), India is sponsoring us through
an extra-mural project, to investigate the
effects of perturbation on metapopulation
dynamics.
individuals in particular subpopulations) would
Effects of migration rate on metapopulations:
stabilize the dynamics of fragmented
How does migration rate affect the dynamics
populations. However, the first experimental
of metapopulations? How does it interact with
study seeking to verify these predictions
subpopulation growth rate to produce the
indicated that the effects of simple localized
observed dynamics? What affects the
perturbations on stability are negligible. In that
synchrony among subpopulations? We are
case, how should one perturb a fragmented
investigating these questions through
46
simulations and laboratory experiments on
Drosophila melanogaster.
Prasad, N.G., Dey, S., Joshi, A. and Vidya, T.N.C.
(2015). Rethinking inheritance, yet again:
inheritomes, contextomes and dynamic
phenotypes. bioRxiv doi:10.1101/013367.
Sah, P. and Dey, S. (2014). Stabilizing spatiallystructured populations through Adaptive Limiter
Control. PLoS One 9(8) e105861.
Tung, S., Mishra, A. and Dey, S. (2014). A
comparison of six methods for stabilizing
population dynamics. Journal of Theoretical
Biology 356:163-173.
Sah, P., Salve, J. and Dey, S. (2013). Stabilizing
biological populations and metapopulations by
Adaptive Limiter Control. Journal of Theoretical
Biology 320:113-123.
Yati, A. and Dey, S. (2011). FlyCounter: A simple
software for counting large populations of small
clumped objects in the laboratory. BioTechniques
51:347-348.
Dey, S. and Joshi, A. (2007). Local perturbations
do not affect stability of laboratory fruitfly
metapopulations. PLoS ONE 2:e233.
47
Evolutionary Biology in Behaviour,
Metabolism & Health
I specialize in not specializing. I used research
more as a tool in education and tried to
motivate undergraduates to identify novel
problems and use a variety of tools to handle
Milind Watve
Professor
[email protected]
them including modeling, simulations,
observations, surveys, meta-analysis, field
experiments as well as lab experiments. Since
students come with a variety of interests and
aptitudes, while catering to them I got into a
diversity of research areas including bacterial
cell division, predatory bacteria, behavior of
Milind Watve obtained PhD from Indian
Institute of Science (IISc), Bangalore, India
and chose a teaching career soon after. He
has taught in Abasaheb Garware College in
Pune for several years before joining IISER
Pune in 2009.
plasmids, behavior of mitochondria, diseases
of wild animals, behavior and infectious
diseases, pollination biology, social behavior,
animal cognition, sex, human behavior and
health. Nevertheless there is a common
theme that runs through all the work, the
connecting thread being evolutionary
biology. I like to give maximum freedom of
ideas and experimental designs to students
and don’t mind if a student’s interest goes
out of the current line of work or away from
my comfort zone.
Areas of current interest: (i) Evolutionary
origins and basic biology behind type 2
diabetes and other age related conditions:
We have completely reinterpreted
metabolic syndrome which has important
implications for clinical practice and drug
discovery. A behavioral intervention protocol
for the reversal of type 2 diabetes is
undergoing clinical trials. (ii) Bacterial life in
calorie restricted environments: Theoretical
and empirical work on oligophilic growth,
aging and asymmetric cell division in
bacteria. (iii) Ecology and evolution of
secondary metabolites of Actinomycetes:
Recently we happened to discover some
novel ecological roles that Actinomycetes
and their secondary metabolites play. This
research has important implications for drug
discovery.
48
Science 100:1695-1700.
Baig, U., Bhadbhade, B., Mariyam, D. and
Baig, U., Belsare, P., Watve, M. and Jog, M.
Watve, M.G. (2014). Protein aggregation in E.
(2011). Can thrifty gene(s) or predictive fetal
coli: Short term and long term effects of
programming for thriftiness lead to obesity?
nutrient density. PloS One 9(9):e107445.
Journal of Obesity 2011:861049.
Kumbhar, C., Mudliar, P., Bhatia, L.,
Lele, U.N., Baig, U.I. and Watve, M.G. (2011).
Kshirsagar, A. and Watve, M. (2014).
Phenotypic plasticity and effects of selection
Widespread predatory abilities in the genus
on cell division symmetry in Escherchia coli.
Streptomyces. Archives in Microbiology
Plos One 6:e14516.
196:235-248.
Joshi, A., Kondekar, S., Belsare, P.,
Watve, M., Bodas, A. and Diwekar, M. (2014).
Ghaskadbi, S., Watve, M. and Jog, M. (2010).
Altered autonomic inputs as a cause of
People with metabolic syndrome disorders
pancreatic beta cell amyloid. Medical
give lower offers in ultimatum game.
Hypotheses 82:49-53.
Psychology 1:128-133.
Baig, U., Bhadbhade, B., Mariyam, D. and
Watve, M.M., Dahanukar, N. and Watve,
Watve, M.G. (2014). Evolution of aging and
M.G. (2010). Sociobiological control of
death: What insights bacteria can provide.
plasmid replication regulation. PLoS One
Quarterly Review of Biology 89(3):209-233.
5:e9328.
Lele, U. and Watve, M. (2014). Bacterial
M.G. (2009). Cooptimization of nectar
growth rate and growth yield: Is there a
content and floral display. Journal of
relationship? Proceedings of the Indian
Bioscience 34:963-967.
National Science Academy 80:531-546.
Dahanukar, N. and Watve, M. (2009). Group
Karve, S., Shurpali, K., Dahanukar, N.,
selection and reciprocity among kin. The
Paranjape, S., Jog, M., Belsare, P. and Watve,
Open Biology Journal 2:66-79.
M. (2011). Money handling and obesity: a
test of the exaptation hypothesis. Current
49
Image: Sengupta Lab
50
Epigenetics, Immunology &
Plant Biology
Anjan Banerjee
Akanksha Chaturvedi
Sanjeev Galande
Krishanpal Karmodiya
Kundan Sengupta
51
Macromolecular Transport and Long
Distance Signaling in Plant Development
Plasticity is an important phenotypic
RNAs (miRNAs) are found to be one of the
disposition of plants as they adapt to the
key components in this network as they
environment. In this regard, the plant’s
target a large number of genes. My primary
vascular system, so called the main highway
research interest is on potato homeobox
in plants, plays a crucial role in the delivery of
genes (KNOX/BELs) and miRNAs in response
nutrients to distantly located organs. The
to various environmental cues such as
phloem, one of the components of plant
photoperiod, biotic and abiotic stress
vascular tissue, functions as a conduit and
responses. Their role as information
constitutes the major long-distance route in
macromolecules in long distance signaling is
this highway. Recent discoveries suggest that
also our research interest. We explore a
the phloem translocation stream not only
combination of bioinformatics and
Anjan Banerjee received his PhD from the
transports photoassimilates, hormones, amino
molecular approaches to investigate the
University of Pune with research work at
acids and proteins but also ferries information
functions in this regard.
Anjan Banerjee
Assistant Professor
[email protected]
National Chemical Laboratory (NCL),
Pune, India. Following postdoctoral work at
Iowa State University, USA, he joined IISER
Pune in 2008.
macromolecules such as mRNAs, small RNAs
(miRNAs) and RNPs that could transfer
information and control the gene regulatory
network in the target organs.
Homeobox genes are ubiquitous in plants
and are involved in plant growth and
development. RNA regulatory networks are
also implied to control a large number of
plant developmental pathways and micro
52
Mahajan, A., Bhogalem S., Kang, I.H.,
Hannapel, D.J. and Banerjee, A.K. (2012). The
a
b
mRNA of a knotted1-like transcription factor of
potato is phloem mobile. Plant Molecular
Biology DOI 10.1007/s11103-012-9931-0.
Banerjee, A.K., Lin, T. and Hannapel, D.J.
(2009). Untranslated regions of a mobile
transcript mediate RNA metabolism. Plant
Physiology 151:1831-1843.
Hannapel, D.J. and Banerjee, A.K. (2009).
Mobile RNA acts as a signal to regulate plant
c
growth and development. U.S. Patent No.
e
7,579,150 issued on August 25, 2009.
Chatterjee, M., Banerjee, A.K. and Hannapel,
D.J. (2007). A BELL1-like gene of potato is light
activated and wound inducible. Plant
Physiology 145:1435-1443.
Banerjee, A.K., Chatterjee, M., Yu, Y., Suh, S.G.,
d
Miller, W.A. and Hannapel, D.J. (2006).
Dynamics of a mobile RNA of potato involved
in a long-distance signaling pathway. Plant
(a) 35S:miR172 overexpression transgenic lines (Solanum tuberosum) in culture medium; (b)
POTH1 homeobox gene expression in stamens of potato flowers; (c) TS of potato stem; (d) Stem
loop RT-PCR of predicted miRNAs in Solanum tuberosum; (e) Micro RNA (miRNA) precursor
structure
Cell 18:3443–3457.
Mazumdar, M., Lee, J.H., Sengupta, K., Ried, T.,
Rane, S. and Misteli, T. (2006). Tumor formation
via loss of a molecular motor protein. Current
Biology 16:1559-1564.
53
Integration of Adaptive and Innate
Receptor Signaling in B Cells
Antibodies are essential in providing
antigen-specific and danger signals into a
protection against many infectious agents.
qualitatively and quantitatively unique
Antibody responses are initiated by B cells
molecular response.
that recognize and respond to foreign
Akanksha Chaturvedi
Assistant Professor
antigens through antigen-specific B cell
receptors (BCRs). In addition to the BCRs, B
cells also express various germline encoded
innate immune system receptors, Toll like
[email protected]
receptors (TLRs) that recognize highly
conserved motifs present in microorganisms.
This dual expression allows B cells to not only
Akanksha Chaturvedi received her PhD
sense antigen but also survey their
from ICGEB, New Delhi, India and took up
environment for danger signals associated
postdoctoral research at the Laboratory of
with the presence of pathogens. How the
Immunogenetics, National Institute of
Allergy and Infectious Diseases (NIAID),
NIH, USA. She joined IISER Pune in January
2013.
The goal of my lab is to determine the
cellular and molecular mechanism by which
B cells integrate BCR and TLR signaling to
modify and tailor antibody responses. In
addition, we also plan to understand how
inappropriate B cell activation by TLRs
potentially results in autoimmunity and even
tumorigenesis.
BCR and TLRs function independently of one
another is known in considerable molecular
details. We know little about the mechanisms
that integrate BCR and TLRs signaling at
subcellular and molecular levels. Although
both BCR and TLRs initiate signal
independently, in response to antigens and
PAMPs, B cells are able to integrate both
54
Chaturvedi, A., Davey, A., Liu, W., Sohn, H. and
Pierce, S.K. (2012). B Lymphocyte Receptors,
Signaling Mechanisms and Activation,
Fundamental Immunology, Ed. W.E. Paul, 7th
Edition Lippincott Williams & Wilkins, USA.
Chaturvedi, A.,* Martz, R., Dorward, D.,
Waisberg, M. and Pierce, S.K.* (2011).
Endocytosed B cell receptors sequentially
regulate MAP kinase and Akt signaling
pathways from intracellular compartments.
Nature Immunology 12:1119 (*corresponding
authors)
Chaturvedi A.,* and Pierce, S.K.* (2009). How
location governs Toll-like receptor signaling.
Traffic 10:621 (*corresponding authors)
Chaturvedi, A., Dorward, D. and Pierce, S.K.
(2008). The B cell receptor governs the
subcellular location of Toll-like receptor 9
leading to hyper-responses to DNA-containing
antigens. Immunity 28:799.
Chaturvedi, A., Siddiqui, Z., Bayiroglu, F. and
Rao, K.V.S. (2002). A GPI-linked isoform of the
IgD receptor regulates resting B cell activation.
Nature Immunology 3:951.
55
Chromatin Biology and Epigenetics
Sanjeev Galande
Professor and Team Leader,
Centre of Excellence in
Epigenetics
[email protected]
Sanjeev Galande obtained his PhD in
Biochemistry from the Indian Institute of
Science, Bangalore, India in 1996. As a
postdoctoral fellow at the Lawrence Berkeley
National Laboratory, USA from 1996-2001, he
Research in our laboratory is focused on
The global chromatin organizer SATB1 has
studying how the dynamic changes in higher
emerged as a key factor integrating higher-
order chromatin assembly govern gene
order chromatin architecture with gene
expression in a spatial and temporal manner.
regulation. Studies in recent years have
To fulfill this, we have established a
unraveled the role of SATB1 in organization of
multidisciplinary program engaged at the
chromatin “loopscape” and its dynamic
interface of biochemistry, molecular biology,
nature in response to physiological stimuli. At
bioinformatics, cell biology, proteomics, and
genome-wide level, SATB1 seems to play a
genomics.
role in organization of the ‘transcriptionally
The packaging of chromatin is hierarchical
and its different states are interconvertible
depending upon the physiological need of
the cell and also contribute in variety of ways
to achieve stringent regulation of gene
activity. Dynamic nature of chromatin loops
studied the role of MAR-binding proteins in
is one such mechanism. Technological
tumorigenesis. He then joined the National
advances in recent years have provided
Centre for Cell Science, Pune, India in 2001 as
unprecedented insights into the role of
a senior scientist. After moving to IISER Pune in
chromatin organization and interactions of
2010, he established the Centre of Excellence
in Epigenetics
various structural-functional components
towards gene regulation.
poised’ chromatin, the part of chromatin
that contains genes that are actively
involved in specific cellular processes. A
major emphasis is on studying epigenetic
modifications, the heritable changes that
influence gene function without changing
DNA sequence. We are particularly
interested in studying the implications of
these phenomena towards development
and differentiation of cells. To accomplish
this, we use a variety of model systems such
as cells of the immune system, stem cells and
cancer cells. We are also interested in
56
studying the global regulatory networks and
signaling during early development. (4) To
the dynamic interplay of various cis and trans
study the dynamics of epigenetic
regulatory elements that dictate patterns of
modifications in human cell types and
gene expression. The outcome of these
uncover its potential association with
studies would be important towards
environment and complex human diseases.
understanding the biology of diseases such
as infectious diseases, cancer and other
complex disorders.
Model systems and ongoing projects
Recently, the repertoire of model systems
used in our laboratory has been expanded
to enable addressing specific questions in
epigenetic regulation. Thus, the centre has
now employed a wide spectrum of model
systems such as yeast, C. elegans, Drosophila
and zebrafish in addition to mouse and
human cells. Using these, we are actively
Kulkarni, R. and Galande, S.# (2014).
Measuring glutathione-induced feeding
response in hydra. Journal of Visualized
Experiments 93:e52178. doi: 10.3791/52178.
Narlikar, L., Mehta, N., Galande, S.#
Arjunwadkar, M.# (2013). One size does not
fit all: On how Markov model order dictates
performance of genomic sequence
analyses. Nucleic Acids Research 41:14161424.
engaged in addressing the following: (1) To
Mir, R., Pradhan, S.J. and Galande, S.#
understand the principles and mechanisms
(2012). Chromatin organizer SATB1 as a novel
of evolution of epigenetic regulation. (2) To
molecular target for cancer therapy. Current
employ genetic, biochemical, molecular
Drug Targets 13:1603-1615.
and computational approaches to
investigate complex and dynamic processes
including transcription, gene regulation, cell
proliferation, self-renewal, regeneration and
interrelationships between these processes.
(3) To understand the role of chromatin
organizer and global regulator SATB1 in Wnt
Khare, S.P., Habib, F., Sharma, R., Gadewal,
N., Gupta, S.# and Galande, S.# (2012).
HIstome--a relational knowledgebase of
human histone proteins and histone
modifying enzymes. Nucleic Acids Research
40(Database issue):D337-342.
57
Epigenetics and
Transcriptional Control in Plasmodium
Malaria is a major public health problem in
Epigenetic and transcriptional regulations,
many developing countries, with Plasmodium
which control vital virulence processes such
falciparum causing the most malaria-
as host cell invasion and cytoadherence, are
associated mortality. Moreover, the
underexplored areas in Plasmodium
emergence of drug-resistant parasites thwarts
falciparum research. Our comprehensive
efforts to control malaria. One of the major
comparative analysis suggests distinct mode
challenges is identification of new drug
of epigenetic regulation in malaria parasite
targets for efficacious, affordable treatment.
(Figure). Furthermore, var genes, which are
Our lab focuses on epigenetic and
involved in virulence and pathogenicity,
transcriptional regulation as potential
have differential epigenetic signatures as
avenues to disrupt the progression of this
they are prominently regulated by H3K9me3
deadly parasite. To accomplish this, our
and H4ac histone modifications, which are
research combines tools from functional
absent on other housekeeping genes
genomics, molecular biology, biochemistry
(Figure). We are also interested in systematic
and computational biology to understand
profiling and integrative analysis of chromatin
the fundamental molecular mechanisms
signatures with chromatin modifiers, HATs and
Cellulaire (IGBMC), Strasbourg, France before
underlying the development of this parasite.
HDACs, which will provide insights into how
joining the Center of Excellence in Epigenetics
The focus is predominantly on the red blood
parasite development is regulated. Our goal
cell stage of development, which is the stage
is to define the dynamic transcriptional
in which all of the clinical manifestations of
regulatory network of the malaria parasite
the malaria disease occur.
and to determine which HATs/HDACs are the
Krishanpal Karmodiya
INSPIRE Faculty Fellow
[email protected]
Krishanpal Karmodiya completed his PhD in
Biology from Jawaharlal Nehru Center for
Advanced Scientific Research (JNCASR),
Bangalore, India in 2008. He was a
postdoctoral fellow at the Institut de
Génétique et de Biologie Moléculaire et
at IISER Pune in 2012.
58
master regulators governing various stages of
parasite development with the goal of
Karmodiya, K.*, Anamika, K., Muley, V.,
targeting these proteins as a way to develop
Pradhan, S.J., Bhide, Y. and Galande, S. (2014).
inhibitors against malaria.
Camello, a novel family of Histone
Acetyltransferases that acetylate histone H4
and is essential for zebrafish development.
Scientific Reports 4:6076. (*corresponding
author).
Karmodiya, K., Krebs, A.R., Oulad-Abdelghani,
M., Kimura, H. and Tora, L. (2012). H3K9 and
H3K14 acetylation co-occur at many gene
regulatory elements, while H3K14ac marks a
subset of inactive inducible promoters in
mouse embryonic stem cells. BMC Genomics
13:424.
Krebs, A.R.,* Karmodiya, K.,* Lindhal-Allen, M.,
Struhl, K. and Tora, L. (2011). SAGA and ATAC
histone acetyl transferase complexes target
distinct sets of genes and ATAC defines a class
of p300 independent enhancers. Molecular
Cell 44:410-23. (*Equal contribution).
Ramya, T.N., Karmodiya, K., Surolia, A. and
Surolia, N. (2007). 15-deoxyspergualin primarily
Model depicting differential occupancies of histone modifications and RNA polymerase II regulating
transcription of housekeeping (top panel) and var (bottom panel) genes in P. falciparum
targets the trafficking of apicoplast proteins in
Plasmodium falciparum. Journal of Biological
Chemistry 282:6388-6397.
59
Chromosome Biology in
Disease and Development
Kundan Sengupta
Assistant Professor
[email protected]
Kundan Sengupta completed his BSc in Microbiology
from St. Josephs College, Bangalore and MSc in
Microbiology from Bangalore University, Bangalore
followed by a PhD in Molecular Biology from Tata
Institute of Fundamental Research, Mumbai, India. His
Recent advances in fluorescent labeling
The current focus of my laboratory is to
technologies combined with high resolution
address two essential facets of nuclear
imaging have revealed remarkable details of
structure-function relationships in cancer cells:
nuclear structure and function. Chromosome
(1) Molecular mechanisms of chromosome
painting studies along with imaging have
positioning (2) Nuclear organization of gene
revealed that chromosomes assume a non-
loci and its relationship with gene expression.
random position in the interphase nucleus.
We are using molecular assays and
Gene rich chromosomes (human
cytogenetic methods such as fluorescence in
chromosome 19) are localized towards the
situ hybridization (FISH), Spectral karyotyping
center, while gene poor chromosomes
(SKY) and laser scanning confocal imaging.
(Chromosome 18) are closer to the nuclear
These studies are in close conjunction with
periphery in human cells. Such an
gene expression studies using microarrays to
arrangement is strikingly conserved in
obtain critical mechanistic insights on nuclear
evolution, strongly suggesting a functional
structure-function relationships.
significance.
postdoctoral research was in Cancer Biology from
the National Cancer Institute (NCI), National Institutes
of Health (NIH), Bethesda, MD, USA and he worked as
a research fellow in Cancer Biology at the Laboratory
of Pathology, Division of Clinical Research, NCI, NIH,
USA. He then joined IISER Pune in July 2010 and is a
Wellcome Trust-DBT Intermediate Fellow since
November 2010.
60
Sharma, K., Iyer, A., Sengupta, K. and
Chakrapani, H. (2013). INDQ/NO, a
bioreductively-activated nitric oxide prodrug.
Organic Letters 15(11):2636-2639.
Paranjape, A.N., Mandal, T., Mukherjee, G.,
Kumar, M.V., Sengupta, K. and Rangarajan, A.
(2012). Introduction of SV40ER and hTERT into
mammospheres generates breast cancer cells
with stem cell properties. Oncogene 31:18961909.
Wang, R.H., Sengupta, K., Li, C., Kim, H.S., Cao,
L., Xiao, C., Kim, S., Xu, X., Zheng, Y., Chilton, B.,
Jia, R., Zheng, Z.M., Appella, E., Wang, X.W.,
Ried, T. and Deng, C.X. (2008). Impaired DNA
damage response, genome instability, and
tumorigenesis in SIRT1 mutant mice. Cancer
Cell 14:312-323.
Sengupta, K., Camps, J., Mathew, P.,
Barenboim-Stapleton, L., Nguyen, Q.T.,
Difilippantonio, M.J. and Ried, T. (2008).
Position of human chromosomes is conserved
(A) Projection of a confocal image of a colon cancer cell (DLD-1) nucleus
labeled with human chromosome 7 and 19 by 3-dimensional fluorescence in
situ hybridization (3D-FISH); (B) 3D reconstruction of the image in (A); (C) Radial
distance measurements of chromosome territories; and (D) DLD-1 nucleus is
flat-ellipsoid in shape (XZ view). Ref: Sengupta et al PloS One, 2007.
in mouse nuclei indicating a speciesindependent mechanism for maintaining
genome organization. Chromosoma 117:499509.
61
Image: Ghose Lab
62
Neuroscience &
Computational Biology
Collins Assisi
Pranay Goel
Aurnab Ghose
M.S. Madhusudhan
Suhita Nadkarni
Raghav Rajan
Nishikant Subhedar
63
Computational Neuroscience
Animals can rapidly detect changes,
Spatial navigation and the hippocampus As
characterize, and respond to a constantly
animals navigate the world, they maintain
changing environment. The richness of this
an internal representation of their own spatial
milieu is reflected in the variety of dynamic
location. The ability to do so has been
patterns that neuronal networks can
attributed, in part, to a structure known as
generate. The goal of my research is to study
the hippocampus. A class of cells in the
how cellular and network properties
hippocampus, termed place cells, responds
constrain the generation of these
with higher activity every time an animal
spatiotemporal patterns and determine their
passes a specific location in space. Distinct
functional role in experimentally well–
units respond at different locations forming a
constrained systems. My work addresses
patchwork that covers the entire space. As
these broad goals within the context of two
the animal moves through space, groups of
University of Mumbai and MSc in Physics from
paradigmatic systems in neuroscience, the
place cells are sequentially activated.
the Department of Physics in Pune University,
hippocampal network and the olfactory
Retaining this spatial and temporal
India. Following a PhD in Complex Systems in
system. I construct and simulate detailed
organization then provides a neural
and idealized models of neuronal networks
instantiation of the memory of a path
to understand the peculiarities these systems
traversed. The goal of this project is to
while also abstracting broad principles
understand how the structure of the network
underlying information processing in the
facilitates the formation of these sequences
brain.
and their subsequent storage as memory
Collins Assisi
Assistant Professor
[email protected]
Collins Assisi completed his BSc from the
2005 at the Center for Complex Systems and
Brain Sciences in Florida Atlantic University, he
moved to The Salk Institute, La Jolla, California
and University of California, Riverside for
postdoctoral research in Computational
Neuroscience. He will be joining IISER Pune in
August 2012.
representations.
64
Encoding and decoding sensory information
Olfactory circuitry provides unique
advantages for the analysis of information
processing by neurons. The task of olfaction
is challenging; it demands the ability to
rapidly detect, identify, categorize, and
prepare for memory storage myriad
Assisi, C.G., Stopfer, M. and Bazhenov, M.
(2011). Using the structure of inhibitory
networks to unravel mechanisms of
spatiotemporal patterning. Neuron 69:373386.
odorants that vary in molecular structure
Assisi, C.G., Stopfer, M., Laurent, G. and
and concentration. Yet, olfaction is
Bazhenov, M. (2007). Adaptive regulation of
achieved by relatively few layers of neurons,
sparseness by feed forward inhibition. Nature
with anatomical structures and physiological
Neuroscience 10:1176-1184.
mechanisms that appear repeatedly in
widely divergent species. Thus, a study of
olfaction offers the promise of insight into a
successful and perhaps optimal biological
algorithm for processing complex
information. The representation of an odor is
Assisi, C.G., Jirsa, V.K. and Scott Kelso, J.A.
(2005). Dynamics of multifrequency
coordination using parametric driving:
Theory and Experiment. Biological
Cybernetics 93:6-21.
transformed as it traverses multiple layers of
Assisi, C.G., Jirsa, V.K. and Scott Kelso, J.A.
the olfactory system from the antenna (or
(2005). Synchrony and clustering in
nose), to the antennal lobe (the insect
heterogeneous networks with global
equivalent of the olfactory bulb in
coupling and parameter dispersion. Physical
mammals) and the mushroom body. My
Review Letters 94:018106.
research examines mechanisms underlying
these transformations and the
computational advantages of transforming
sensory representations from one layer to
the next in the olfactory system.
65
Dynamical Systems Modeling of
Multiscale Phenomena in Biology
Pranay Goel
Assistant Professor
[email protected]
Dynamical processes in biology naturally
responsible for function. Additionally, we are
span several systems and multiple scales,
also now working on modeling glucose-
both in space and in time. We are interested
sensitive neurons of the brain towards a view
in studying the dynamical behavior of
to understanding their potential role in
biological processes through mathematical
maintaining energy homeostasis. A recent
modeling to complement experimental
direction of work in our lab relates to analysis
understanding. My research focuses primarily
of data collected from patients diagnosed
on theoretical neuroscience, cardiac
with Type 2 diabetes. This is joint work with
dynamics and diabetes. Each of these areas
researchers at the University of Pune and K.
is rich with issues that arise from a
E. M. Hospital, Pune.
fundamental need to develop theoretical
Pranay Goel received his PhD in Physics at
the University of Pittsburgh, USA. His
postdoctoral work was carried out at the
Mathematical Biosciences Institute, The
Ohio State University, and at the
Laboratory of Biological Modeling, NIDDK,
National Institutes of Health, USA. He joined
the Mathematics and Biology faculty at
IISER Pune in 2009.
frameworks, and to handle multiscale
dynamics within those.
Our understanding of glucose-stimulated
Although we are a dry lab, since such
research is highly interdisciplinary in nature,
we collaborate extensively with
experimentalists.
insulin secretion from the pancreatic
endocrine tissue, the islets of Langerhans, has
developed considerably over the last three
decades. Much of my recent work has been
related to analyzing some newly proposed
models of islet voltage oscillations (called
“bursting”) that implicate both ionic as well
as metabolic activity as being jointly
66
Goel, P. and Sherman, A. (2009). The geometry
of bursting in the dual oscillator model of
pancreatic beta-cells. SIAM Journal on
Applied Dynamical Systems (SIADS) 8:16641693.
Goel, P., Sherman, A. and Friedman, A. (2009).
Multiscale modeling of electrical and
intracellular activity in the pancreas: The islet
Tridomain equations. SIAM Multiscale Modeling
and Simulation 7:1609-1642.
Zhang, M., Fendler, B. Peercy, B., Goel, P.,
Bertram, R., Sherman, A. and Satin, L. (2008).
Long lasting synchronization of calcium
oscillations by cholinergic stimulation in
isolated pancreatic islets. Biophysical Journal
95:4676-4688.
Higgins, E.R., Goel, P., Puglisi, J.L., Bers, D.M.,
Cannell, M. and Sneyd, J. (2007). Modeling
calcium microdomains using homogenization.
Journal of Theoretical Biology 247:623-644.
A mathematical model of calcium cycling during excitation-contraction coupling
in the heart cell (for details, please see Higgins et al., 2007). The geometry captures
some of the essential complexity of the problem: an incredibly narrow—compared
to the scale of the myocyte—dyadic cleft mediates calcium signalling in the
sarcomere, and ultimately, the function of the cell.
Goel, P., Sneyd, J. and Friedman, A. (2006).
Homogenization of the cell cytoplasm: The
calcium bidomain equations. SIAM Multiscale
Modeling and Simulation 5:1045-1062.
67
Development and Function
of Neural Circuits
We are interested in exploring the
unique length scales where mechanical
development, design and plasticity of
tension may be exploited to mediate
neuronal circuits.
feedback mechanisms playing an important
Wiring up the nervous system
Aurnab Ghose
Assistant Professor
[email protected]
Aurnab Ghose obtained his PhD from the
Beatson Institute for Cancer Research, UK. He
was a postdoctoral fellow at the Department
of Cell Biology, Harvard Medical School, USA
before joining IISER Pune in 2008.
Axonal pathfinding and establishment of
synaptic connectivity require instructive
remodeling of the actin and microtubule
role in neuronal signaling and development.
The role of mechanical tension in neuronal
morphogenesis is being investigated using
quantitative force measurement techniques.
cytoskeletons. We have identified a set of
Design principles and plasticity of neuronal
novel cytoskeletal regulators that influence
circuits
axonal outgrowth and pathfinding in vivo.
Innate behaviours, like the feeding drive,
Our current studies, employing cell
aggression, fear and courtship, are under
biological, biophysical and dynamic imaging
strong selective pressure and have significant
approaches, are directed towards
hardwired components in their underlying
identifying the mechanisms engaged by
circuitry. While the latter ensures stereotyped
these players during development.
outputs, these behaviours are also malleable
Mechanical forces in neuronal development
and function
Physical forces, like mechanical tension
along neuronal processes, represent a higher
to experience. We are attempting to unravel
the design principles and the mechanisms of
plasticity in the neuronal circuitry subserving
aggression and feeding-related behaviours.
order integration of cytoskeletal activities
and membrane dynamics. Neurons offer
68
Sharma, A., Rale, A., Utturwar, K., Ghose, A. and
Subhedar, N. (2014). Identification of the CART
neuropeptide circuitry processing TMT-induced
predator stress. Psychoneuroendocrinology
50:194-208.
Akash, G., Kaniganti, T., Tiwari, N. K., Subhedar, N.
K. and Ghose, A. (2014) Differential distribution
and energy status-dependent regulation of the
four CART neuropeptide genes in the zebrafish
brain. Journal of Comparative Neurology
522(10):2266-2285.
Sahasrabudhe, A., Vittal, V. and Ghose, A. (2013)
Peeping in on the cytoskeleton: Light microscopy
approaches to actin and microtubule
organization. Current Science 105 (11):1562-1570.
Sahasrabudhe, A. and Ghose, A. (2012).
Cytoskeletal remodeling in the establishment of
the neuronal circuitry. IISc Journal 92 (4):403-410.
Mukherjee, A., Subhedar, N. K. and Ghose, A.
(2012). Ontogeny of the Cocaine- and
amphetamine-regulated transcript (CART)
neuropeptide system in the brain of zebrafish,
Danio rerio. Journal of Comparative Neurology
520:770-797.
Ghose, A. and Shashidhara, L. S. (2011). Cyclin
beyond the cell-cycle: new partners at the
synapse. Developmental Cell 21(4):601-602.
69
Biomolecular 3D Structure Modeling
M.S. Madhusudhan
Associate Professor
Alliance Senior Fellow
[email protected]
M S Madhusudhan got a PhD from the
Molecular Biophysics Unit of the Indian Institute
of Science in 2000. This was followed by post-
The broad aim of our research is to
identify appropriate sources of spatial
accurately model the 3D structures of
restraints (http://mspc.bii.a-star.edu.sg/click)
proteins and their complexes. To this end, we
and characterize the local environments
combine experimental observations,
and functions of the modeled structures
statistical knowledge and the laws of physics
(http://mspc.bii.a-star.edu.sg/depth).
to develop computational methods in
Besides predicting/modeling the 3D
structural biology. Using the modeled 3D
structures of proteins, protein-ligand (small
structures, we investigate the function of the
molecule), protein-protein and protein-
modeled proteins/complexes. While the
DNA/RNA complexes, we are now
methods are broadly applicable, they are
developing methods to design these
tested on particular systems of interest, often
molecules and complexes.
in close collaboration with experimentalists.
Our research gives detailed information of
cellular processes and hence impacts
doctoral stints at the Rockefeller University
research on human health, nutrition and
and the University of California at San
biology as a whole. The models we build
Francisco. Since 2008 he was principal
utilize spatial restraints, such as distances,
investigator at the Bioinformatics Institute of
Singapore and joined IISER Pune in 2013.
angles, volumes etc. that are taken from
template structures, extracted from
experimental data, deduced using
computational tools, or from a combination
of the above. Our computational tools
70
Doan, D.N.P., Li, K-Q., Vasudevan, S. and
Madhusudhan, M.S. (2012). Transplantation of
a hydrogen bonding network from West Nile
virus protease onto Dengue-2 protease
improves catalytic efficiency and sheds light
on substrate specificity. Protein Engineering
Design and Selection 25:843-850.
Braberg, H., Webb, B., Tijoe, E., Pieper, U., Sali,
A. and Madhusudhan, M.S. (2012). SALIGN: A
multiple protein sequence/structure alignment
web server. Bioinformatics 28:2072-2073.
Nguyen, M.N. and Madhusudhan, M.S. (2011).
Biological insights from topology independent
comparison of protein 3D structures. Nucleic
Acids Research 39:e94.
Nguyen, M.N., Tan, K.P. and Madhusudhan,
M.S. (2011). CLICK--topology-independent
comparison of biomolecular 3D structures.
Nucleic Acids Research 39:W24-W28.
Tan, K.P., Varadarajan, R. and Madhusudhan,
M.S. (2011). Depth: A Web server to compute
depth and predict small-molecule binding
cavities in proteins. Nucleic Acids Research
39:W242-W248.
71
Computational Modeling
of Neuronal Pathways
Biophysics of synaptic transmission in normal
sophisticated neural components that allow
function and pathological states
for ‘In-Silico’ experiments and make testable
Synaptic transmission is essential to all
information processing in the nervous system.
Suhita Nadkarni
[email protected]
Suhita Nadkarni obtained her BSc and MSc
(Physics) in 1998 from University of Mumbai;
and PhD in Physics from Ohio University in
2005. After postdoctoral work at the Center
for Theoretical Biological Physics, University of
California, San Diego and Computational
Neuroscience Laboratory at the Salk Institute,
La Jolla, Suhita will be joining IISER Pune in
August 2012.
Changes in the strength of synaptic
transmission, termed synaptic plasticity, is the
cellular underpinning of learning and
predictions. It is not always possible, owing to
technological limitations, to make direct
measurements. This modeling paradigm can
serve as a bridge between experiments and
theory.
memory. Synapses are specialized
Calcium hypothesis of Alzheimer’s Disease
components of neuronal networks
(AD)
comprising a plethora of molecular signaling
Calcium is a key molecule in synaptic
cascades that operate over multiple
transmission that finely orchestrates synaptic
timescales to give rise to intricate
plasticity mechanisms called Long-Term
spatiotemporal patterns of activity. Minute
Potentiation (LTP) and Long-Term Depression
components of this complex system can
(LTD) directly involved with memory
have far reaching consequences that
formation and deletion. In a rare inherited
transcend levels of organization, from
form of AD it is seen that the intracellular
molecules to behavior. Our ultimate goal is
calcium signal is severely disrupted. Recent
to understand the contribution of each of
studies have suggested that this remodeling
these pathways to higher level function.
of the calcium signal is the basis of cognitive
Our approach is to devise realistic
biophysical computational models of these
dysfunction seen early on in AD. This project
aims to quantify each of the molecular
cascades involved in the disruption of
72
calcium signaling as seen in AD leading up
to aberrant LTP and LTD. Since the
impairment of mental function precedes
typical structural changes defined by
plaques of beta amyloids, this line of
investigation can provide valuable insights
into pathogenesis of the disease.
Modeling astrocyte–neuron signaling
Astrocytes are ubiquitous non–neuronal cells
in the brain that send out processes that
often envelop a synapse. More recently, the
idea of a third component participating in
Nadkarni, S., Bartol, T., Stevens, C., Levine, H.
and Sejnowski, T.J. (2012). Short-term
plasticity constrains spatial organization of a
hippocampal presynaptic terminal.
Proceedings of the National Academy of
Sciences 109:14657-14662.
Nadkarni, S., Bartol, T.M., Sejnowski, T.J. and
Levine, H. (2010). Modeling vesicular release
at hippocampal synapses. PLoS
Computational Biology 6:e1000983.
synaptic transmission is gaining traction.
Nadkarni, S., Jung, P. and Levine, H. (2008).
Astrocytes are not electrically excitable like
Astrocytes optimize synaptic transmission of
neurons. However, they respond to stimuli
information. PloS Computational Biology
with an elevated level of calcium that
4:e1000088.
spreads across cells in the form of a traveling
wave thus providing a complementary
signaling circuit. Their ability to release a
variety of neuro-modulators like glutamate,
Adenosine Triphosphate (ATP) and D-serine in
Nadkarni, S. and Jung, P. (2003).
Spontaneous oscillations in dressed neurons:
A new mechanism for epilepsy? Physical
Review Letters 91:268101.
response to calcium elevation ensures
multiple levels of interaction with neuronal
networks. This project aims to develop
computational models of vesicular
glutamate release from astrocytes and the
effect of ATP release from astrocytes on
neuronal networks.
73
Neurobiology of
Movement Initiation
Raghav Rajan
Ramalingaswami Fellow
[email protected]
Raghav Rajan completed his PhD in
neuroscience with Dr Upinder Bhalla at the
National Centre for Biological Sciences,
Bangalore, India in 2006. He did his
postdoctoral research in neuroscience with Dr
Allison Doupe at the University of California at
San Francisco, USA and joined IISER Pune in
2013.
Movements are ubiquitous in our lives. With
Songbirds are a well-studied animal model
extensive repetition every day, even complex
for learned motor sequences. The learned
learned movement sequences like speech
song sequence of an adult zebra finch
become automatic and we hardly notice
comprising of a stereotyped song sequence
initiating them. The importance of movement
of acoustic elements, has many parallels to
initiation is more apparent in diseases like
human speech. My postdoctoral research on
Parkinson's disease, where movement
song initiation suggested that adult zebra
initiation becomes difficult. Yet, how the brain
finches “warm-up” with a variable number of
initiates learned movement sequences and
short introductory vocalizations before
why movements fail to initiate in disease
initiating their song sequence. Using various
conditions remains poorly understood. In my
techniques to record and manipulate the
lab, we use the zebra finch, a songbird, as a
activity of individual neurons in awake
model system to understand how the brain
singing birds, current research in my lab is
initiates learned movement sequences.
focused on examining the neural processes
that underlie this “warm-up”, with the goal of
understanding how the zebra finch brain
initiates the learned song sequence.
74
Woolley, S.C., Rajan, R., Joshua, M. and
Doupe, A.J. (2014). Emergence of contextdependent variability across a basal ganglia
network. Neuron 82(1):208-223.
Rajan, R.# and Doupe, A.J. (2013). Behavioral
and neural signatures of readiness to initiate
a learned motor sequence. Current Biology
23:87-93. (# corresponding author)
Rajan, R., Clement, J.P. and Bhalla, U.S.
(2006). Rats smell in stereo. Science 311:666670.
Spectrogram representation of one song bout of an adult male zebra finch
One song bout is shown as a spectrogram with frequency on the y-axis and time on the x-axis. The
darkness represents the power in the particular time-frequency band. Individual sounds are called
syllables and given character labels as shown in blue on the spectrogram. This example bout begins
with 5 repetitions of a short syllable called an introductory note (IN, represented by the letter 'i'). The
motif consists of a stereotyped sequence of 4 syllables (represented by 'a', 'b', 'c' and 'd') interleaved
by silent periods (gaps). In this bout, the bird repeats his motif twice.
75
`
Glucose Sensing Mechanisms
in the Zebrafish Brain
Our studies show that the neurons of the
entopeduncular nucleus may integrate the
entopeduncular nucleus in the brain of
information on energy status and
teleosts play a crucial role in processing
reproductive maturity is under investigation.
energy metabolism-related information. The
Nishikant Subhedar
Visiting Faculty
neurons and their fibers contain cocaineand amphetamine-regulated transcript
(CART) and neuropeptide Y (NPY); the
agents are known to process hunger and
[email protected]
satiation in the brain of vertebrates. The two
systems seem to work antagonistically. CART
system is up regulated with improved energy
Nishikant Subhedar, PhD, FNASc, obtained
supply, and NPY with energy depletion.
PhD at Nagpur University, India and did his
Output from these systems seems to regulate
postdoctoral work at University of Florida and
feeding behavior and rate of metabolism.
University of Kentucky, USA. He served as a
Currently we are testing the possibility that
Professor of Pharmacology at the Department
of Pharmaceutical Sciences, Nagpur
University, India for several years before joining
IISER Pune in 2008.
We are also engaged in studying the central
actions of CART in a rodent model. Our data
suggest that while CART in hypothalamicamygdala circuitry may be involved in
anxiety and fear, hypothalamic-nucleus
accumbens shell circuitry may process
reward and reinforcement. CART also serves
to promote learning and formation of spatial
memory, and play an important role in drug
addiction.
the neurons of entopeduncular nucleus may
also serve a role in glucose sensing. The
neurons of this nucleus are sensitive to the
sex steroid hormones and may play an
active role in the regulation of the LH cells in
the pituitary gland and eventually influence
reproduction. The possibility that the
76
Subhedar, N., Barsagade, V.G., Singru, P.S.,
Thim, L. and Clausen, J.T. (2011). Cocaineand amphetamine-regulated transcript
peptide (CART) in the telencephalon of the
plays a role in the manifestation of
depression: social isolation and olfactory
bulbectomy models reveal unifying
principles. Neuropsychopharmacology
34:1288–1300.
catfish, Clarias gariepinus: Distribution and
Dandekar, M.P., Singru, P.S., Kokare, D.M.,
response to fasting, 2-deoxy-D-glucose,
Lechan R.M., Thim, L., Clausen, J.T.,
glucose, insulin, and leptin treatments.
Subhedar, N.K. (2008). Importance of
Journal of Comparative Neurology 519:1281–
cocaine-and amphetamine-regulated
1300.
transcript peptide (CARTp) in the central
Barsagade, V.G., Mazumdar, M., Singru, P.S.,
Thim, L., Clausen, J.T. and Subhedar, N.K.
(2010). Reproductive phase-related
nucleus of amygdala in anxiogenic
responses induced by ethanol withdrawal.
Neuropsychopharmacology 33:1127–1136.
variations in cocaine- and amphetamine-
Mazumdar, M., Sakharkar, A.J., Singru, P.S.
regulated transcript (CART) in the olfactory
and Subhedar, N. (2007). Reproduction
system, forebrain and pituitary of the female
phase-related variations in neuropeptide Y
catfish, Clarias batrachus (Linn.). Journal of
immunoreactivity in the olfactory system,
Comparative Neurology 518:2503–2524.
forebrain and pituitary of of the female
Nakhate, K.T., Kokare, D.M., Singru, P.S. and
Subhedar, N.K. (2010). Central regulation of
catfish, Clarias batrachus (Linn.). Journal of
Comparative Neurology 504:450–469.
feeding behavior during social isolation of
Singru, P.S., Mazumdar, M., Sakharkar, A.J.,
rat: evidence for the role of endogenous
Lechan, R.M., Thim, L., Clausen, J.T. and
CART system. International Journal of Obesity
Subhedar, N.K. (2007). Immunohistochemical
35:773–784.
localization of cocaine- and amphetamine-
Dandekar, M.P., Singru, P.S., Kokare, D.M.
and Subhedar, N.K. (2009). Cocaine- and
amphetamine-regulated transcript (CART)
regulated transcript peptide in the brain of
the catfish, Clarias batrachus (Linn.). Journal
of Comparative Neurology 502:215–235.
77
Awards and Honors
Faculty Members
2013-2014
Krishanpal Karmodiya INSPIRE Faculty Award 2013
Gayathri Pananghat INSA Young Scientist Medal 2014 • Innovative Young Biotechnologist Award (IYBA) for 2013, Department of
Biotechnology (DBT) •DST- INSPIRE Faculty Fellowship
Raghav Rajan DBT Ramalingaswami Re-entry Fellowship
2012-2013
Neelesh Dahanukar DST- INSPIRE Faculty Fellowship
Nishikant Subhedar’s research paper from his group titled “Nicotine evoked improvement in learning and memory I mediated
through NPY Y1 receptors in rat model of Alzheimer’s disease” has been selected for the Olson Prize awarded by the Journal
Peptides
2011-2012
Ramana Athreya One of the seven finalists of the prestigious Whitley Fund for Nature Awards of UK. He received the award at
the hands of HRH The Princess Royal for his contributions to nature conservation and empowering the locals in Arunachal
Pradesh. The award includes a research grant of GBP 30,000.
Sanjeev Galande Elected as a Fellow of the Indian National Science Academy (FNA) for the year 2012
Thomas Pucadyil Elected as Young Associate of the Indian Academy of Sciences, Bangalore
2010-2011
Sutirth Dey Awarded Young Scientist Medal of the Indian National Science Academy, New Delhi, India
Sanjeev Galande Selected for the Shantiswaroop Bhatnagar Award-2010 by the Council of Scientific and Industrial Research
(CSIR), New Delhi and was elected as the Fellow of the Indian Academy of Sciences, Bangalore, India
78
L.S. Shashidhara Awarded JC Bose Fellowship of the Department of Science and Technology, Government of India
Milind Watve Elected as a Fellow of the Indian National Science Academy, New Delhi, India
2009-2010
Nagaraj Balasubramanian DBT Ramalingaswami Re-entry Fellowship
Anjan Banerjee Elected to the Membership of Plant Cell Culture Association of India
Sutirth Dey Awarded the guest fellowship of Wissenschaftskolleg zu Berlin
L.S. Shashidhara Awarded the Shanti Swarup Bhatnagar Prize for the year 2008 in Biological Sciences for his contribution to the
understanding of appendage development in animals
2006-2007
L.S. Shashidhara Elected as a Fellow of Indian National Science Academy (INSA), New Delhi and as a Fellow of Indian Academy
of Sciences, Bangalore
79
Awards and Honors
Students
Niraja Bapat Best Poster Award at the Origins 2014 conference, the second joint International conference of ISSOL
(http://www.issol.org) and Bioastronomy (Commission 51 of the International Astronomical Union) held in Nara, Japan during July
6-11, 2014
Srishti Dar First prize for Poster Presentation on Inhibition of Dynamin-Catalyzed Membrane Fission by the Accessory Endocytic
Protein Sorting Nexin 9, at Lipid-protein Interactions in Membranes: Implications for Health and Disease, a BiophysicalSociety
Sponsored Meeting 11-POS at Centre for Cell and Molecular Biology Hyderabad in 2012 (Abstract published in Biochemical Journal)
http://www.biochemj.org/bj/news/poster_winners/Dar_S.htm)
Abhinav Parivesh Dr Manasi Ram Memorial Prize for best paper presentation by young scientists in poster session" at the XXXVI All
India Cell Biology Conference held at Bhabha Atomic Research Centre, Mumbai from October 17-19, 2012
Aparna Sherlekar DBT Travel Support to attend 2014 American Society for Cell Biology (ASCB)/International Federation for Cell
Biology (IFCB) Meeting in Philadelphia, PA, December 6-10, 2014
Ankitha Shetty ERASMUS Experts for Asia Grant for 6 months to work in the laboratory of Prof. Riitta Lahesmaa at Turku Center for
Biotechnology, Turku, Finland
T. Shreeharsha DBT Travel Grant to travel to the 9th International Workshop on Molecular Biology and Genetics of the
Lepidoptera held in August 2014 in Crete Greece; Best Poster Award at the EMBO Workshop on Upstream and downstream of
Hox genes held in December 2014 in Hyderabad
Jay Prakash Shukla Best Poster Award in Biology Science Day, IISER Pune
L.A. Viswanathan DST Travel Grant to present a poster at the Dynamics of Cellular Behavior during Development and Disease
meeting, Cold Spring Harbor Asia's conference, held November 17-21, 2014 in Suzhou, China
80
Conferences and Workshops
INSA-LEOPOLDINA Symposium on Human Evolution towards Language: From
Genes to Behaviour
January 15-16, 2015
Brain Circults: Eighth Edition of SERB School in Neurosciences
December 8-21, 2014
35th Annual Meeting of Plant Tissue Culture Association (India) & National
Symposium on Advances in Plant Molecular Biology & Biotechnology
March 10-12, 2014
Biophysics Paschim 6
March 1, 2014
Asian Conference on Raptor Research
February 6-7, 2014
International Symposium on Protein Structure, Function and Dynamics
January 30, 2014
Hippocampus: From Synapses to Behavior
December 1-3, 2013
Symposium on Evolution of Human Cognition
November 17-19, 2013
Principles of Autonomous Neurodynamics: The 10th Annual Meeting of the
Society for Autonomous Neurodynamics (SAND)
August 5-7, 2013
Workshop and Symposium on X-ray Diffraction
January 19, 2013
Symposium on Cell Compartmentation, Division and Signalling
April 10-11, 2012
Mini-Symposium on Modern Biology
September 28-29, 2011
Third SERC School in Neuroscience
December 7-21, 2008
Indo-Sokendai Meeting on Trends in Modern Biology
October 24-25, 2008
81
Extramural Funding at
IISER Pune Biology
Apart from institutional funds, Biology discipline at IISER Pune has been receiving extra-mural funding from external
funding agencies. This funding has been generated through competitive research proposals put together by
individual faculty members in Biology.
82
Grant
Funding Source
Active grants in IISER Bio
Research Grants
11
Research Grants
Department of Biotechnology
(DBT)
DST-SERB
Wellcome Trust Alliance Senior Fellowship
Wellcome Trust-DBT Alliance
2
Wellcome Trust Alliance Intermediate
Fellowship
Wellcome Trust Alliance Early Career
Fellowship
Ramalingaswamy Fellowship
7
2
Department of Biotechnology
(DBT)
Department of Science and
Technology (DST)
1
INSPIRE Faculty Award
4
3
Data as of December 2014
83
Infrastructure at IISER Pune
With modern laboratories, high-performance computing facilities and audio/video
enabled classrooms, IISER Pune is well set-up for research and teaching activities.
Research in biology is supported by basic as well as advanced equipment in welldesigned laboratory spaces for experimental and computational work. Some of the
facilities include fly facility, greenhouse, animal cell and tissue culture facility, imaging
centre and outsourced animal house.
84
85
Student Life at IISER Pune
Both IISER Pune campus and Pune city offer a vibrant environment to
complement the academic pursuits of students. Campus housing and
dining facilities are available for all students at quick reach to working
and learning spaces of the campus as are the multitude eating out
options outside the campus. Students get to interact with the larger
scientific community brought together at IISER Pune through the
national and international conferences hosted by the institute. Various
student clubs at the institute actively organize events related to art,
music, drama and dance within the campus. Opportunities for social
outreach can be explored through Disha and Prarambh, two outreach
initiatives by students and faculty members at the institute.
86
87
Getting to Pune
The Cultural Scene
The Western Ghats
Pune is connected by Air to the major
Pune is one of the major cultural centers
The richly biodiverse Western Ghats are
cities across the country. The airport at
of the country. Home to several Indian
mountain ranges that run parallel to the
Lohegaon doubles as an air force base.
classical music and dance traditions,
west coast of India. The Sahyadri hill
Pune is also well connected by trains. It is
Pune is also home to many renowned
range housing major hill stations such as
one of the major hubs for the rail network
artists. It also hosts a series of annual
Matheran, Lonavala-Khandala, and
in the western part of the country. Pune is
music festivals ranging from Indian
Mahabaleshawar and many other
also accessible from Mumbai by road,
Classical to Jazz. Most notable among
ecological hotspots are within reachable
which is a 3-hour drive. The Mumbai
these is the annual Savai Ghandharva
distances to Pune as are some of the
international airport has a regular taxi
Music Festival. Pune is also home to the
spectacular beaches in this part of the
service to Pune. Regular bus service runs
National Film Institute and National Film
country.
between the two cities as well.
Archives and hence boasts of a rich
celluloid heritage. It also hosts the annual
Pune Film festival.
88
Photo Contributions by
Nagaraj Balasubramanian
Anjan Banerjee
Deepak Barua
Apurva Barve
Abhinav Parivesh
89
Indian Institute of Science Education and Research (IISER) Pune
Dr. Homi Bhabha Road, Pashan, Pune 411008, INDIA
Phone: +91 20 25908001
Web: www.iiserpune.ac.in

Biology at IISER Pune

Transcription

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