Assistant Professor/Associate professor, SUNY-Buffalo.
- 1989, Postdoctoral Associate, University of Iowa, IA.
Assistant Professor, G.N.D. University, India.
Postdoctoral Associate, Frankfurt university, Germany.
Ph.D. (Molecular Biology).
Tata Institute of Fundamental Research, Bombay, India.
1973, M.Sc. Honors (Physics). Punjab University, Chandigarh, India
Complete sequencing of human and other genomes has
pointed to an extremely important role played by genes in many diseases. In
particular, mutations in various ion channels and related genes have been linked
to a large number of neurological and cardiovascular disorders. Genomic
information also highlights the strong evolutionary conservation of molecular
mechanisms. This makes the use of genetic model systems, such as Drosophila,
very powerful for understanding molecular mechanisms underlying most biological
phenomena, including neuromuscular disorders.
Using genetic protocols developed in our laboratory, we have identified more
than 15 novel mutations that produce striking alterations in calcium and
potassium currents in Drosophila. These mutations also affect other
functions in flies, such as locomotor ability, heart rate, and/or sensitivity to
the toxic effects of drugs that act on ion channels. Cloning and molecular
analysis of nine genes, and the gene products disrupted by these
mutations, is underway in the laboratory. Some of these genes are
completely novel, with nothing known about them in any organism. This analysis
is yielding important information on modulation and regulation of ion channels,
and their essential role in maintaining cellular physiology.
In addition to identifying and studying the above mutations, we are using existing mutations to analyze modulation of calcium channels via signal transduction pathways. Combining mutations with pharmacological agents that disrupt specific signal transduction components, we have shown that the L-type calcium channels in Drosophila are modulated via the PLC - DAG - PKC pathway and a pathway involving PACAP, PAC1 receptors, adenylyl cyclase, cAMP, and PKA.
in Refereed Journals:
R., Triggle, D. J. and Singh, S. (2001) Regulation of L-type of calcium channels
in pituitary GH4C1
cells by depolarization. J. Biol. Chem., (accepted for publication).
M., Gu, G.-G. and Singh, S. (2000) Mutations
Affecting the Delayed Rectifier Potassium Current in Drosophila. J.
R., Padmanabhan, S., Rutledge, A, Singh S. and Triggle, D. J.(2000) Permanently
charged chiral 1,4-dihydropyridines: molecular probes of L-type calcium
channels. Synthesis and Pharmacological characterization of methyl
calcium channel antagonists. J. Med. Chem. 43:2906-2914.
P., Gu, G-G., Chen, D., Free, S. J. and Singh, S. (1999)Mutational Analysis of
the Shab-encoded Delayed Rectifier K+
channels in Drosophila. J. Biol. Chem. 274,22109-22113.
A., and Singh, S. (1999) Unmasking of a Novel Potassium Current in Drosophila
by a Mutation and Drugs. J. Neurosci. 19, 6838-6843.
A., Gu., G.-G. and Singh S. (1999) Modulation
of the Dihydropyridine-Sensitive Calcium Channels in Drosophila by a cAMP-Mediated
Pathway. J. Neurobiol. 39, 491-500.
D., Bhattacharya, A. and Singh, S. (1998) Blockade
of the Delayed Rectifier Potassium Current in Drosophila by Quinidine and
Related Compounds. J. Neurogenet. 12: 25-39
G.-G. and Singh, S. (1997) Modulation of the dihydropyridine-sensitive Ca2+
channels in Drosophila by a phospholipase C-mediated pathway. J.
D. and Singh, S. (1997) Selective blockade of the delayed rectifier potassium
current by tacrine in Drosophila. J. Neurobiology 32: 1-10
M. L., Gu, G.-G. and Singh, S. S. (1995) Resolution and pharmacological analysis
of the voltage-dependent calcium channels of Drosophila larval muscles.
J. Neuroscience 15:6085-6093
G.-G. and Singh, S. (1995) Pharmacological
analysis of heart beat in Drosophila.
J. Neurobiology 28: 269-280
M. and Singh, S. (1994). Developmental
temperature selectively regulates a voltage-activated potassium current in Drosophila.
J. Neurobiol. 25, 119-126
S. (1993). Quantification of
countercurrent distribution: from molecular partition to animal behavior.
Biochem. Biophys. Res. Comm.196: 430 - 434
A. K., Singh, S., Rathe, P. and Wu, C.-F. (1990).Mutational and gene-dosage
analysis of calcium-activated potassium channels in Drosophila :
Correlation of micro- and macroscopic currents. Neuron 4: 313-321
S. and Wu, C.-F. (1990). Properties
of potassium currents and their role in membrane excitability in Drosophila
larval muscle fibers. J. Exp. Biol. 152: 59-76
S. and Wu, C.-F. (1989). Complete
separation of four potassium currents in Drosophila. Neuron 2:
C.-F., Tsai, M.-C., Chen, M.-L., Zhong, Y., Singh, S. and Lee, C.Y. (1989).
Actions of dendrotoxin on K+
channels and neuromuscular transmission in Drosophila melanogaster and
its effects in synergy with K+
channel-specific drugs and mutations. J. Exp. Biol. 147: 21-41.
P., Jen, P. H.-S. and Singh, S. (1988). Auditory
spatial sensitivity of inferior collicular neurons of echo locating bats. Brain
Res. 456: 127-138.
S., Bhandari, P., Chopra, M. J. S. and Guha, D. (1987).Isolation of autosomal
mutations in Drosophila melanogaster without setting up lines. Molec.
Gen. Genet. 208: 226-229.
G., Singh, S. and Sripathi, K. (1984). Audiograms
of a South Indian bat community. J. Comp. Physiol. 154: 133-142.
P. and Singh, S. (1983). Unmasking
in neurons of the inferior colliculus of Eptesicus fuscus with binaural
stimulation. Hearing Res. 10: 331-343.
S. (1983). A mutagenesis scheme for
obtaining autosomal mutations in Drosophila . Ind. J. Exp. Biol. 21:635-636.
S. and Siddiqi, O. (1981). torpid
, a new sex linked temperature paralytic mutation in Drosophila melanogaster.
Molec. Gen. Genet. 181: 400-402.
A., Lakhman, S. S. and Singh, S. Modulation of L-type Calcium Channels in Drosophila
by Pituitary Adenylyl Cyclase Activating Polypeptide
R., Aletta, Singh, S. and Triggle, D. J. Comparative evaluation of
potencies of clinical second generation 1,4-dihydropyridines.
G.-G., Getman, P and Singh, S. Properties of L-type Ca2+
currents in Drosophila larval muscle fibers.
S. and Wu, C.-F. (1999). Ionic currents in the larval muscles of Drosophila.
In: International Review of Neurobiology (Vol. 43 -Neuromuscular
Junctions in Drosophila). V. Budnik and S. Gramates, eds. Academic
Press. pp. 191-220.
S., Chopra, M. J. S., Bhandari, P. and Guha, D. (1989). Isolation of
autosomal behavioral mutations in Drosophila
In 'Neurobiology of Sensory Systems', (R. N. Singh and N. J.
Strausfeld, eds) Plenum Press, NY, pp 419-426.