The research work of the Division of
Pathophysiology is related to the understanding of pathogenesis of
different diarrhoeagenic bacteria, development of candidate vaccine,
Super ORS and use of proper antibiotics against diarrhoea. The
scientists of this division have been working on different projects.
Highlights of some of the projects are as follows:
One of the studies reveals that oral immunization of rabbits by heat
killed Shigella flexneri 2a can give 100% protection against
shigellosis. Immune response has also been studied in details and a
34kDa outer membrane protein (OMP) has been identified as a
protective antigen. This study may lead to develop a simple,
practical and effective vaccine against shigellosis. Presently the
purification of 34kDa OMP has been done along with its biophysical
as well immunological characterization.
In another study the intracellular signal transduction pathway
involved in the induction of intestinal secretion by E.coli
heat-stable toxin (STa) has been evaluated. It has been shown that
besides cyclic Guanosine -3’,5’- mono phosphate E.coli STa also
involves phosphatidyl-inositol specific phospholipase C, inositol
trisphosphate, diacylglycerol, calcium and protein kinase C in its
mechanism of action in a human colonic carcinoma cell line COLO-205.
Work is also going on to find out the cytoskeletal rearrangements
caused by E.coli STa.
It has also been noted that the heat-stable enterotoxin secreted by
non-O1 V.cholerae (NAG–ST) causes IP3–mediated Ca++ release from
intracellular store, which then stimulates nitric oxide production
by activating nitric oxide synthase (NOS). This nitric oxide through
soluble cGMP activates calcium influx.
Recently, it has been shown that E.coli STa downregulates the cell
proliferation through Protein Kinase G –Mitogen Activated Protein
Kinase pathway and has been considered as a potent anti-angiogenic
and anti- metastatic molecule.
Calcium Sensing Receptor (CaSR) is one of the important receptor,
which can sense and causes the influx of extracellular calcium ions
[Ca++o] with the subsequent rise of intracellular calcium level [Ca++i]
and associates with fluid secretion. In the Division the cloning of
the full-length cDNA of Calcium Sensing Receptor (CaSR) from a colon
carcinoma cell line COLO-205 has been done. Moreover, the
involvement of CaSR in the intracellular signaling mechanism of
virulence factors secreted by different enteric bacteria (E.coli
heat stable enterotoxin, Thermostable Direct Hemolysin) has been
observed with the help of inhibitor, si-RNA transfection etc. The
results reveal that CaSR is involved in the thermostable direct
hemolysin-mediated downregulation of colonic carcinoma cell
The studies of this Division in rat perfusion model have shown that
hypotonic ORS made by lowering sodium is much more effective than by
The pathogenic mechanism of nonO1, nonO139 V.cholerae is not yet
known clearly. In a study at this Division two forms of
Hemagglutinin Protease (HAP), one is mature 45-kDa and processed
35-kDa forms have been purified in the presence and absence of EDTA
from culture supernatants of PL-21, which is a nonO1, nonO139
strains. Enterotoxigenicities of both forms of HAP are tested in
rabbit ileal loop (RIL), Ussing chamber and tissue culture assays.
The two forms show functional differences from each other. The
35-kDa form shows hemorrhagic fluid response in RIL, decrease in the
intestinal short-circuit current in Ussing chamber experiment and
cell rounding effect on HeLa cells. In contrast the 45-kDa form
shows an increase in intestinal short-circuit current in an Ussing
chamber experiment and a cell distending effect on HeLa cells. The
results suggest that HAP may be an important virulence factor of
Apart from this, the scientists of the division are also involved in
teaching and other academic activities of different Universities and
professional societies in India. A large number of students have
been trained in this laboratory for their Ph.D./ M.Sc./ M.Tech.
program. Several collaborative projects are also going on with many
National and International Scientists of different Organizations and