|
| |
| Dr.
BHUPENDRA NARAIN SINGH |
|
| |
|
|
 |
... |
Scientist
Division of Microbiology
CDRI
|
| |
| |
| E-Mail |
bnsingh@cdri.res.in
|
| Phone |
+91-0522-2612411-18 Ext 4211 |
| Educational
qualifications |
M.Sc., Ph.D.
(B.H.U., Varanasi) |
| Date of birth |
July 28, 1965 |
|
| |
| Postdoctoral
Research |
| |
| |
| |
| AREA
OF RESEARCH |
| |
|
• |
Molecular
Genetics, Molecular Microbiology, and Functional Genomics |
|
| |
| Ongoing
research projects in lab: |
| • |
Regulation
of kas operon genes expression in mycobacteria:
Mycobacteria possess both
fatty acid synthase type I (FAS-I) and fatty acid synthase
type II (FAS-II) systems. FAS-I is a single polypeptide
with multiple catalytic activities that generate several
shorter Co-A esters and create precursors for elongation.
FAS-II consists of disparate enzymes which elongate
palmitoyl-ACP to unusually long carbon chain fatty acids.
Elongation pathway in M. tuberculosis is accomplished
by the concerted action of genes residing at two loci
(one contains kas operon genes, other contains mabA
and inhA genes). Isoniazid (INH) and ethionamide, both
inhibitors of mycolic acid synthesis, inhibit the
FAS-II elongation pathway leading to progressive depletion
of mature mycolates, which in turn induces
the transcription of kas operon genes. We have delineated
the kas operon locus in M. aurum and are characterizing
H37Rv kas operon upstream regulatory elements using
M. aurum as surrogate strain.
Conserved organization of kas operon genes in M. tuberculosis
H37Rv and M. aurum (Acc. No. DQ268649).
|
• |
Screen
system for target based screening of anti-mycobacterial
drugs: Promoter inducible assays, a preferred
alternative over conventional drug screening, are basically
recombinants carrying reporters like ß-galactosidase
or luciferase genes fused to promoters that specifically
respond to certain types of antibiotic stress. We have
created a recombinant M. aurum strain using the H37Rv
kas operon promoter in fusion with ß-gal reporter
gene. Recombinant strain showed continued expression
of reporter gene throughout the growth but responds
to the | inhibition of long chain fatty acid synthesis
by increased synthesis of ß-gal enzyme. The inhibiting
response of drugs is monitored by a simple ß-gal
enzyme assay. This kind of screen system renders advantage
over others as they enable a systematic screen of compounds
interfering with a given metabolic pathway. The screen
system is in use for the screening of antimycobacterial
compounds as potential FAS II inhibitors.
(Neeta Gupta and B N Singh, Journal of Applied
Microbiology 105 (2008): 1703–1710)
|
• |
Functional
genomics of sigma factors using knockout mutants of
M. smegmatis: Sigma factor SigF controls the
expression of virulence-associated genes and is believed
to contribute to the pathology of tuberculosis. It was
reported to be absent in fast growing nontuberculous
mycobacteria until its orthologs were reported recently
in database. For the first time we showed the presence
of sigF gene in non-pathogenic mycobacteria. We analysed
the sigF expression in M. smegmatis and showed that
unlike its late stage expression in M. tuberculosis
and M. bovis, found in earlier studies, sigF is expressed
throughout the growth in M. smegmatis, by and large,
at same level, but its expression varies upon exposure
to different stress conditions. This suggests that apart
from regulating the virulence genes expression in pathogenic
mycobacteria, SigF is likely to have more
roles in the mycobacterial physiology. We created deletion
in sigF gene of M. smegmatis mc2155 strain and continuing
with the study of its regulon.
M. smegmatis mc2155: wild type (MS), sigF mutant (SFKO1)
and complemented (SFKO1/sigF)
(A K Singh and B N Singh, Current Microbiology
(2008): 56, 574-580)
|
•
|
Differential
expression of sigH paralogs in M. smegmatis:
Mycobacterium smegmatis genome is predicted to encode
26 sigma factors, which is twice the number present
in M. tuberculosis (13 sigma factors). There is an enrichment
of sigH subfamily that contains seven paralogs in this
species. SigH, an extracytoplasmic function sigma factor,
is a key regulator of a transcriptional network that
responds to oxidative and heat stresses in mycobacteria.
To analyze the role of these paralogs in M. smegmatis,
we examined the expression of sigH paralogs at different
stages of growth and under various stress conditions
using quantitative real time RT-PCR. sigH and its paralogs
are differentially expressed during growth stages and
in response to different stress conditions. Variable
expressions of sigH paralogs during growth stages suggest
a role for these sigma factors in regulating stage-specific
gene expression. Several of them are induced in response
to heat and oxidative stress, which is a central feature
of sigH sigma factor. Characterization of some of these
paralogs is in progress.
(A K Singh and B N Singh, Journal of Bacteriology
(2009): 191(8), 2888-2893) |
|
| RESEARCH
GROUP |
Present Students |
| • |
Anirudh K.
Singh (Senior Research Fellow, CSIR)
Rajesh K Biswas (Senior Research Fellow, CSIR)
Debashis Dutta (Junior Research Fellow, CSIR)
Kumari Kripalata (Junior Research Fellow, ICMR)
Vandana Singh (Project Assistant) |
| |
• |
Neeta Gupta (Awarded Ph.
D) - presently Post Doctoral Fellow at ICGEB, New Delhi.
|
|
| PUBLICATIONS |
| |
| • |
Anirudh
Kumar Singh and Bhupendra N. Singh.
Differential expression of sigH paralogs during growth
and different stress conditions in Mycobacterium smegmatis.
Journal of Bacteriology (2009): 191(8),
2888-2893. |
| • |
Anirudh
Kumar Singh and Bhupendra N. Singh.
Conservation of sigma F in mycobacteria and its expression
in Mycobacterium smegmatis. Current Microbiology
(2008): 56, 574-580. |
| • |
Neeta
Gupta and Bhupendra N Singh. Deciphering
kas operon locus in Mycobacterium aurum and genesis
of a recombinant strain for rational based drug screening.
Journal of Applied Microbiology (2008):
105, 1703-1710. |
| • |
Amritha
Suresh, Vanya. Shah, Deepa S. Rani, Bhupendra
N. Singh, G. Uma Prasad, S. Subramanian, Satish
Kumar and Lalji Singh. A mouse gene encoding a novel
member of the WD family of proteins is highly conserved
and predominantly expressed in the testis (Wdr13). Molecular
Reproduction and Development (2005): 72, 299-310.
|
| • |
Bhupendra
N. Singh, Amritha Suresh, G. Uma Prasad, S.
Subramanian, Mehar Sultana, Sandeep Goel, Satish Kumar
and Lalji Singh. A highly conserved human gene encoding
a novel member of WD-repeat family of proteins (WDR13).
Genomics (2003): 81, 315-328. |
• |
Bhupendra
N. Singh and B. S. Srivastava. Gene Therapy.
Drugs and Pharmaceuticals (2001): 24(2), 1-4. |
• |
S.
C. Lakhotia and Bhupendra N. Singh.
Synthesis of a ubiquitously present new HSP60 family
protein is enhanced by heat shock only in the Malpighian
tubules of Drosophila. Experientia (1996):
52, 751-756. |
• |
Bhupendra
N. Singh and S. C. Lakhotia. The non-induction
of HSP70 in heat shocked Mapighian tubules of Drosophila
larvae is not due to constitutive presence of HSP70
or HSC70. Current science (1995): 69(2),
178-182. |
• |
S.
C. Lakhotia and Bhupendra N. Singh.
A simple and inexpensive Western-blotting apparatus.
Ind. J. of Exp. Biology (1993): 31, 301-302. |
| |
|
|
| |
|
| |
|