Area of Research
Bacterial/Parasite/Mammalian DNA Replication and cell cycle regulation
lab in JNU is actively engaged in studying the unique characteristics of
DNA replication and cell cycle regulation in two medically important
pathogens, Plasmodium falciparum and Helicobacter pylori.
Both these pathogens are extremely important although poorly understood
from the basic biology point. Not a single effective vaccine is available
for either of these pathogens. There are reports of drug resistant strains
too. Our aim is to find the key regulators in DNA replication processes so
that we can identify potential targets for therapy.
The DNA replication process offers various
important and interesting targets for new inhibitors development.
Understanding the mechanism of initiation of DNA replication in P.
falciparum and H. pylori will be useful in finding new targets
for screening new antibiotics to eradicate these pathogens. We have
already identified two such targets (PfGyrase for P. falciparum and
HpDnaB helicase for H. pylori).
INSTITUTION AND LOCATION
University, West Bengal, India
University, West Bengal, India
Jawaharlal Nehru University, New Delhi, India
1997-1998 Research Assistant, Dept. of Microbiology, University of Virginia,
1998-2001 Post-Doctoral Fellow, Dept. Of Pathology, Harvard Medical
School, Boston, USA
2001-2005 Asstt. Professor, Special Centre for Molecular Medicine, Jawaharlal
Nehru University, New Delhi, India
2005- Associate Professor, SCMM, JNU, New
2002-2003 Visiting Fellow, Dept. of Pathology, Harvard Medical School,
2003-2004 Visiting Fellow, Harvard School of
Public Health, Boston, USA (summer)
Visiting Fellow, Bernard Nocht Institute for Tropical Medicine,
2008 Humboldt Fellow, Bernard Nocht Institute for Tropical Medicine,
1. The Wellcome Trust,
1/1/2005 to 31/12/2009
Functional Characterization of replication
initiation proteins of Plasmodium falciparum
Indo-Swedish Link grant
1/1/2007 to 31/12/2009
restart mechanism in Helicobacter pylori
Fellowship awarded by Department of Science and Technology 1/5/2009 to 30/4/14
Control of DNA
replication initiation and cell cycle regulation in two important human
pathogens: Plasmodium falciparum and Helicobacter pylori.
Awards and honours
Junior Research Fellowship, Council of Scientific and Industrial
Research, Govt. of India
1994-1997 Senior Research Fellowship, Council of Scientific and
Industrial Research, Govt. of India
Training grant in emerging infectious diseases, National Institute of
Post doctoral fellowship in breast cancer, Breast cancer research
programme, Department of Army, USA
2002 International reviewer panel, Medical Science Monitor
Patent Application Approved by US Patent Office on "GEMININ AND ORC3N
INHIBIT REPLICATION OF HERPESVIRUSES, PAMILOMAVIRUSES AND POLYOMAVIRUSES" BY
DUTTA, A AND DHAR S.K. No. B0801.70253US00
2005-2009 Wellcome Trust Senior International Research Fellowship, Wellcome
2007 Swarnajayanti Fellowship, Department of Science and
Technology, Govt. of India
2008 Alexander Von Humboldt Fellowship awarded by Humboldt
Biological Chemistry, Molecular Microbiology, FEBS Journal, Medical Science Monitor and
various Indian journals.
American Society for Microbiology
Elected member of Guha
Research Conference (2007)
published from JNU after setting up independent laboratory:
Sharma A., Nitharwal RG., Singh B., Dar A.,
Dasgupta A and Dhar SK. (2009) Helicobacter pylori
single-stranded DNA binding
protein-functional characterization and modulation of H. pylori
DnaB helicase activity. FEBS J. 276: 519-531
Gupta, A., Mehra P. and Dhar SK. (2008).
Plasmodium falciparum origin recognition complex subunit 5:
functional characterization and role in DNA replication foci formation.
Mol. Microbiol. 69:
Mehra P., Srivastava S., Shivange AV., Gupta A., Roy N and Dhar SK.
(2008) Nicotinamide inhibits Plasmodium falciparum Sir2
activity in vitro and parasite growth.
FEMS Microbiol Lett.
Nitharwal RG, Paul
S, Soni RK, Sinha S, Prusthy D, Keshav T, RoyChoudhury N, Mukhopadhyay G,
Chaudhury T, Gourinath S, and
Dhar SK (2007)
The domain structure of
DnaB helicase: The N-terminal domain can be dispensable for helicase
activity whereas the extreme C-terminal region is essential for its
function. Nucleic Acids Res.
Dar MA, Sharma A, Mondal N and Dhar SK. (2007) Molecular
cloning of apicoplast targeted Plasmodium falciparum DNA gyrase
genes: unique intrinsic ATPase activity and ATP-independent dimerisation
of PfGyrB subunit. Eukaryotic Cell. 6:398-412.
Gupta A, Mehra P,
Nitharwal R, Sharma A, Biswas AK and Dhar SK.
(2006) Analogous expression pattern of Plasmodium falciparum
replication initiation proteins PfMCM4 and PfORC1 during the asexual and
sexual stages of intraerythrocytic developmental cycle. FEMS
Microbiol. Lett. 261:12-8.
(2005) Expression and characterization of human malaria parasite
Plasmodium falciparum origin recognition complex subunit 1.
Biophys Res Commun.
Mehra P, Mukhopadhyay G and Dhar SK. (2005)
DnaB helicase can bypass E. coli DnaC function in vivo.
Soni RK, Mehra P, Choudhury NR, Mukhopadhyay G,
Dhar SK. (2003) Functional characterization of
Helicobacter pylori DnaB helicase. Nucleic Acids
Dhar, S. K$., Soni R. K.,
Das, B. K. and Mukhopaddhyay, G. (2003) Molecular Mechanism of
Action of Major Helicobacter pylori Virulence Factors.
Molecular and Cellular Biochemistry 253:207-15 ($corresponding
Jha S, Karnani N, Dhar SK, Mukhopadhayay K, Shukla S, Saini P,
Mukhopadhayay G, Prasad R. (2003). Purification and
characterization of the N-terminal nucleotide binding domain of an ABC
drug transporter of Candida albicans: uncommon cysteine 193
of Walker A is critical for ATP hydrolysis. Biochemistry
Mondal, N., Soni, R.K., and Mukhopaddhyay, G. (2002). A ~35 kDa
polypeptide from baculovirus infected insect cells binds to yeast ACS like
elements in the presence of ATP. BMC Biochemistry
2002, 3:23 ($corresponding
Wohlschlegel, J.A., Dutta, A. and
Dhar, S.K. (2002). ORC and the Initiation of DNA
Replication. Chemtracts: Biochemistry and Molecular Biology
and Dhar S. K. (2005)
Diseases and Cure: a molecular approach in
“Microbes: Health and Environment” edited by Prof. Ajit Varma.
Publisher I. K. International. Delhi. India.
Papers from post-doctoral research:
(2007) Mcm10 and And-1/CTF4
recruit DNA polymerase alpha to chromatin for initiation of DNA
Dhar SK$, Saxena S, Yuan P,
Senga T, Takeda D, Robinson H, Kornbluth S, Swaminathan K, Dutta A. (2004)
A dimerized coiled-coil domain and an adjoining part of geminin interact
with two sites on Cdt1 for replication inhibition. Mol Cell.
15:245-58. $Co-first author.
Mondal N, Zhang Y, Jonsson Z, Dhar SK, Kannapiran M, Parvin JD. (2003)
Elongation by RNA polymerase II on chromatin templates requires
topoisomerase activity. Nucleic Acids Research
Wohlschlegel, J.A., Dhar, S. K., Prokhorova,
T. A., Dutta, A. and Walter, J. C. (2002) Xenopus Mcm10 binds to
origins of DNA replication after Mcm2-7 and stimulates origin-binding of
Cdc45. Mol. Cell 9(2):233-40
Dhar, S.K., Yoshida, K., Machida, Y., Khaira, A., Chaudhuri, B.,
Wohlschlegel, J.A., Leffak, M., Yates, J. and Dutta, A. (2001)
Replication from oriP of Epstein-Barr Virus requires human ORC and
is inhibited by geminin. Cell 106(3), 287-96.
Dhar, S.K., Delmolino, L. and Dutta A. (2001) Architecture of
the human origin recognition complex. J. Biol. Chem.
Jonsson, Z.O, Dhar, S.K., Narlikar, G.J.,
Auty, R., Wagle, N., Pellman, D., Pratt, R.E., Kingston, R. and Dutta A.
(2001) Rvb1p and Rvb2p are essential components of a chromatin
remodeling complex that regulates transcription of over 5% of yeast
genes. J. Biol. Chem. 276(19), 6279-88
Wohlschlegel, J.A., Dwyer, B.T., Dhar, S.K.,
Cvetic, C., Walter, J.C., Dutta, A. (2000) Inhibition of eukaryotic DNA
replication by geminin binding to Cdt1. Science 290(5500),
Thome, K.C., Dhar, S.K., Quintana, D.G., Delmolino, L., Shahsafaei,
A. and Dutta A. (2000) Subsets of human ORC subunits are expressed in
non-proliferating cells and associate with non-ORC proteins. J.
Biol. Chem. 275(45), 35233-41
Dhar, S.K. and Dutta, A. (2000).
Identification and characterization of the human ORC6 homolog. J.
Biol. Chem. 275(45), 34983-87
Papers from Pre-doctoral
Dhar, S.K., Vines, R.R., Bhattacharya, S. and Petri, W.A., Jr. (1998).
Ribosomal DNA fragments enhance the stability of transfected DNA in
Entamoeba histolytica. Jr. of Euk. Microbiol. 45(6), 656-660.
Olvera, A., Olvera, F., Vines, R.R., Ricillas-Targa, F., Lizardi, P.M.,
Dhar, S.K., Bhattacharya, S., Petri, W.A. and Alejandro Alagon (1997)
Stable transfection of Entamoeba histolytica trophozoites by
lipofection. Arch. of Med. Res. 28, S49-51
Dhar, S.K., Royhoudhury, N., Mittal, V., Bhattacharya, A. and
Bhattacharya, S. (1996). Replication initiates at multiple random
sites in the ribosomal DNA plasmid of the protozoan parasite Entamoeba
histolytica. Mol. Cell. Biol. 16, 2314-2324.
Dhar, S.K., Roychoudhury, N., Bhattacharya, A. and Bhattacharya, S. (1995).
A multitude of circular DNAs exist in the nucleus of Entamoeba
histolytica. Mol. Biochem. Parasitol., 70, 203-206.
Sehgal D, Mittal V, Ramachandran S, Dhar SK, Bhattacharya A,
Bhattacharya S. (1994) Nucleotide sequence organisation and analysis of
the nuclear ribosomal DNA circle of the protozoan parasite Entamoeba
histolytica. Mol Biochem Parasitol. 67:205-14.