1.

Name of the area/division : BASIC RESEARCH IN MODERN BIOLOGY

Areas covered: Biochemistry, Cell & Molecular Biology, Structure Biology & Biophysics,
Cellular & Molecular Immunology, Microbiology, Plant Molecular Biology, Synthetic,
Systems & Chemical Biology, Reproductive & Developmental Biology etc.
2. Overview: Basic research efforts are directed at conceiving and developing fundamental new
ideas, approaches, and methods for addressing some of the most intriguing and challenging
aspects of the living organisms through support to investigator-initiated frontier research in life
science, on the basis of scientific excellence.
Objectives: Support Research and Development in emerging areas of modern biology and
initiate programmes in frontier and emerging areas.

A. Strategy for implementation of programs: The department has constituted a Task Force on
Basic Research in Modern Biology comprising of experts from various field of life
science. The Task Force guides the department in the implementation of programme,
identifying thrust area in Modern Biology and generating new projects in the emerging
areas. The division implements
programme by various approaches mostly through
individual schemes bottoms-up approach, multi-centric /network programme etc.
B. Monitoring and mentoring: Projects are being monitored through a well-established review
process by experts. The scientific and technical progress reports of ongoing projects are
evaluated through Task Force and special Expert/Review Committee. New proposal, are
evaluated by a rigorous mechanism which involves presentation by the PI in the Task
Force meeting. The Task Force meets twice/thrice in a year. The department
also
mentors young researchers/ scientists by conducting Task Force meetings in different
centres/institutes for their active participation in the meetings, and also by attaching Task
Force members with them for developing proposals.

3. Publications: Figure showing average number of publications in peer reviewed indexed

journals.

Research and

50
43

45

40

40
35

30

32

Number

30
25
20
15
10
5
0
2008-2009

2009-2010

2010-2011

2012-2013

Year
4. Significant achievement:
Cell and Molecular Biology:
Studies conducted on elucidating the role of signalling pathways involving C3G in cellular
plasticity have led to the identification of a novel cellular regulator that specifically interacts
with and inhibits the activity of oncogenic Bcr-Abl, but not that of cellular Abl kinase. The
results have also shown elevated expression of TC48 and activation of the endogenous
expression can inhibit proliferation and enhance therapeutic response of CML cells.
Work conducted to study the Regulation of sister chromatid recombination by ATM and ATR
kinases has shown the role of both ATM as well as ATR in regulating homologous
recombination (HR). However, only ATR was shown to suppress long-tract gene conversion
associated with HR. The data obtained for the first time show that ATM and ATR distinctly
regulate sister chromatid recombination during DNA double-strand break repair.
Research being conducted on expression and trafficking of cell surface adhesion molecules and
their contribution to endometrial receptivity have led to the identification of the cell surface
protein repertoires of endometrial epithelial cell lines which may be of relevance in embryoendometrial adhesion. These studies have also revealed the role of Rab Coupling Protein (RCP)
in the trafficking of integrin alpha v to the cell surface of endometrial epithelium.

Study initiated on Role of FtsH Protease in Escherichia coli cell division have for the first time
revealed, the role of the essential protease FtsH, in bacterial cell division. Since FtsH protease
is present in many pathogenic bacteria, besides playing an essential role in the regulation of cell
division the protease could in future be developed into a potential antibacterial target.
Studies carried out on Type II phosphatidylinositol phosphate kinase function have led to the
discovery of new class of enzymes that regulates cellular communication system, that are
important in the context of many diseases such as Type II diabetes mellitus and in future may
lead to the discovery of novel therapeutic strategy.
Research on elucidating spatio-temporal regulation between cohesin and chromatin in
executing faithful chromosome segregation during meiotic cell cycle has shown the role of
kinetochore in pairing of homologous chromosomes and chromosome condensation, which are
the key processes for the faithful chromosome segregation.
Research work carried to understand the molecular functions of E2F1 in a tumour
microenvironment in the X15-myc oncomouse model of hepatocellular carcinoma have
established the dual role of transcription factor E2F1 in tumorigenesis. E2F1 facilitated cellular
proliferation by stimulating genes involved in cell cycle control and replication during early
stages of hepatocarcinogenesis. However, during late stages, E2F1 triggered replicational
stress-induced DNA damage and sensitized cells to apoptotic death in a p53-independent
manner.
Biochemistry and Biophysics:
Studies on Vibrio Cholerae cytolysin has provided insights into the mode of action of Vibrio
cholerae cytolysin (VCC), which is considered as a prominent model toxin in the family of
bacterial -barrel pore-forming toxin. The study indicates a novel mode of regulatory
mechanism imposed by a lectin activity site within the VCC toxin. Further work is being
carried out to explore the details of the structural basis of such regulatory mechanism(s) in the
context of the mode of action of the VCC toxin.
The group working on elucidating the role of MAP kinase directed phosphatases in Toll like
receptor signaling mediated protective Th 1 type immunity have for the first time identified that
tumor necrosis factor receptor-associated factor (TRAF)3, a negative regulator of TLR pathway
plays a critical role in the establishment of visceral infection.
Research work being carried out to understand the role of different domains on the stability of
interferon- induced human guanylate binding protein has led to the identification of a novel
DxEKGD motif in hGBP1. The truncated and mutant proteins showed that both the alpha helix

of the intermediate region and the motif plays critical role in the stimulation of the activity
which may be related with antiviral activity of the protein.
Research work being carried out to unravel the role of human non-coding satellite-III
transcripts in cellular stress response have shown novel role for a long non-coding RNA in
transcriptional silencing. The study has demonstrated that Satellite 3 transcripts are essential
for the human cells to mount heat shock response and that the cell do not survive if these
transcripts are knocked down. Further they have also shown that the Satellite 3 transcripts
suppress transcriptional activity during heat shock by recruiting transcription factors. (Fig1)

Fig.1 Representative images showing the expression pattern of satellite 3 transcripts (pink color
speckles) in the nucleus (blue color) of HeLa cells upon exposure to heat shock or other forms of
physiological stressors as indicated.

Cancer Biology:
Group working on simultaneous inhibition of plasminogen system along with matrix
metalloproteinase in controlling angiogenesis have newly synthesized phthalazine compound
and platinum-azo compound which can be used as small molecule inhibitor. Isoquinilone
another compound synthesized by the same group could be used as imaging molecules for
cancer cells .
Studies carried out on characterization of functional interaction between estrogen receptor and
ETS transcription factor in breast cancer cells have revealed a positive co-relative expression of
ESE1 with ER in breast cancer patients and showed poor patient survival. It is also shown that
ESE1 expression may lead to ER-negative breast cancer phenotype. Further work is being

carried out to determine binding regions of these two proteins to design a peptide which can
prevent their interaction.
Microbiology:
Studies on iron uptake mechanism in mycobacteria has demonstrated for the first time a new
pathway for iron acquisition in M.tuberculosis which would be important in understanding the
mechanism of bacterial survival during TB. Using protein chemistry, molecular biology and
microscopy techniques it is shown that human holo-transferrin interacts with GAPDH both in
vivo (Fig. 2a) and in vitro (Fig. 2b).

Fig. 2a: TEM image demonstrating the binding of transferrin-gold particles on the
surface of M.tuberculosis H37Ra.

Fig. 2b: Co-immunoprecipitation experiments indicate that transferrin specifically

interacts with
and M.tb GAPDH present in the cell wall fraction of M.tuberculosis
H37Rv. Cell wall fractions
of M.tuberculosis were incubated with biotinylated human holo-transferrin, interacting proteins were
captured by streptavidin paramagnetic particles. Western blot analysis was done with alpha-GAPDH
antibody.

Study conducted on Molecular characterization of DacD (a putative DD-carboxypeptidase) of

Escherichia coli have for the first time revealed the biochemical property of DacD through in
vitro biochemical analyses which is supported by in silico studies. In vitro characterization of
DacD is indeed a major step towards understanding how three homologous proteins (PBP5,
PBP6 and DacD) are involved in exerting different or partially overlapping cellular activity at
different time points of various growth phases.

Cellular and Molecular Immunology:

Work on Notch activated signaling cascades and the consequences for T-cell homeostasis have
shown that Notch activity - characterized by interactions in the cytoplasm of cells - is critical
for T-regulatory cell survival and likely an important regulator of its function.
Study being conducted to understand the molecular events involved in inhibition of DC
activation/maturation by HGF has demonstrated the molecular basis for HGF-induced DC
inhibition and provides the first evidence for an involvement of Btk in proximal signaling
events induced by HGF.
Research work to elucidate the role of Apoptosis-inducing factor (Aif) in T lymphocyte
development have shown that aif- hypomorphic harlequin (Hq) mice show thymic
hypocellularity and a cell- autonomous thymocyte developmental block associated with
apoptosis at the -selection stage, independent of T cell receptor- (TCR) recombination.
These data indicate that Aif, a ubiquitous protein, serves a lineage-specific non-redundant antiapoptotic role in the T cell lineage by regulating ROS during thymic -selection.

Structure Biology and Chemical Biology:

Work on Morpholino-based antisense-Synthesis and
its application has successfully
developed methods for making modified Morpholino-based antisense and has also shown
successful application in cancer cells. (Fig. 3)

Fig. 3: Fixed cell image (40X) of HEK 293T, MCF-7, PC-3 and Shh Light II cells for cellular intake of
BODIPY-GMO pentamer 1. BODIPY-GMO concentration: 2.5 mM, Incubation time 16 h.
Visualization by labelling with green dye. PC-3 is prostate cancer cells, MCF-7 is breast cancer cells.
HEK 293T and Shh Light II are normal cells.

Identified the role of motif in geminivirus replication. The work has revealed that conserved
residues in Rep that probably form a loop / -hairpin structure interacts with ssDNA while
residues in the motif located outside the loop are involved in coupling ATP induced
conformational change to DNA binding.

High resolution X-ray crystal structures of two enzymes, Salmonella typhimurium 2methylcitrate synthase (2-MCS) and acetate kinase (StAckA) has been determined. These
enzymes have provided the basis for understanding the molecular basis for the specificity of the
enzymes towards substrates and plausible mechanism of catalysis. (Fig. 4)

Fig. 4: S. typhimurium methyl citrate synthase decamer structure

Vascular Biology:
Investigation being carried out to elucidate signaling mechanism of sFRP4 mediated inhibition
of angiogenesis has shown for the first time that secreted frizzled related protein 4 (sFRP4) can
inhibit angiogenesis both in-vivo and in vitro conditions. The excessive leakiness of endothelial
monolayer is coupled with increased ROS levels that promote the endothelial cells to undergo
apoptosis.

5. Project supported so far (2007-2012 only, statistics, Bar diagram etc.)

83

90

Number of projects

80
65

70

59

60
46

43

50
40
30

18

20
10
0

Year

6. Others downloadable forms for the scheme (if any) as applicable to particular scheme
(MoU, Asset acquired certificate, UC & SE etc.)
7. Calls for proposals: (A) Issued so far (B) The next call date tentative:
A. Call issued so far: Call for Concept Papers for Research Proposals on Systems Biology of
Metabolic Diseases and Infectious Diseases (2011)
B. Next Call Date: By the end of this year
8. Contact address (Head and Program Officer: Name, designation, email id, phone, fax etc.)
Head: Shri Arvind Duggal, Adviser, DBT New Delhi-110003. E.mail: duggal.dbt @nic.in
Telefax: 011-24361215.
Programme Officer: Dr. Manish Rana, Scientist-C, DBT New Delhi-110003. E.mail:
manish.rana@nic.in Tel: 011-24363726.