Life Sciences Division,
AU-KBC Research Center
MIT,
Chromepet, Chennai 600044
(tel)
+91-44-2-223-4885 (fax) +91-44-2-223-1034
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Research Interests
Intercellular Permeation of Macromolecules
Molecules of size ~1 nm play an important role in signal
transduction pathways inside cells as well as in intercellular coupling.
The rate of permeation of these molecules through intercellular pathways
(gap junctions) is an important parameter that sets the scope of
coordinated tissue function. For example, in sparsely innervated tissue
(e.g. large vascular vessels), gap junctional communication acts a
conduit for the propagation of neuronally stimulated input to the rest
of the non-innervated tissue. This mechanism of coordination also
applies in tissues (e.g. pancreatic islets) where cells directly
influenced by hormones and metabolites from the blood stream would
influence cells remote from these agents. We are studying the influence
of the nature of the diffusing agent as well as the nature of the gap
junction channels on the permeation mechanism. Elucidating the
mechanism may have an impact in understanding the role of permeating
agents in suicide gene therapy.
Macromolecular Permeation through Nanopores
Biological polymers of cross-section 12A can permeate various
biological pores of dimension 15A and above. The permeability of such
molecules is approximately 1/1000 of that of ions. Various groups have
shown that, when ssDNA permeates hemolysin channels, the ion flow across
the channel is interrupted. The hope is that specific changes in the
current level can be correlated to the nature of the particular chemical
moiety traversing the narrow part of the channel. We are examining gap
junctions channel (15A) and porins (15-20A) in this context. Particular
circumstances (slow gating, poor voltage dependence of gating and other
related biophysical characteristics) make these channels particularly
good candidates for studying DNA translocations and interactions.
Modeling of
Syncytial Coordination
Intercellular coupling i.e. coupling of intracellular biochemical
pathways plays an important role in syncyctial coordination. We are
developing a quantitative understanding of the role of intercellular
gap junction communication in tissue function. We are
currently modeling the steady state response of a single vascular smooth
muscle (VSM) cell. This model will be integrated
into a scheme for syncytial coordination, where intercellular pathways
for the flow of ions and larger macromolecules will be linked to
intracellular second-messenger pathways. We are also collaborating
with Dr. Christ (Albert Einstein College of Medicine) on models of
arterial smooth muscle where both calcium sparks and calcium waves play
a role in vasoconstriction through different calcium-release mechanisms.
The Center already has a 8-machine Beowulf cluster for molecular
modelling, and the algorithms for intercellular coordination will be
parallelized using the PVM/MPI message passing model. When the number of
modelled cells in a tissue increases to the envisaged 10000, distributed
algorithms currently offer the only cost-effective way to reduce
execution times.
Information Extraction from the
Biological Literature
The Center has a computational linguistic group; members
of this group are collaborating with biologists to develop novel ways
of extracting useful information from published biological
literature (such as the Medline Abstracts) using Natural Language
Processing (NLP) tools and techniques.
Biosensors
This is still incomplete.
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Life Sciences Division,
AU-KBC Research Center
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MIT,
Chromepet, Chennai 600044
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(tel)
+91-44-2-223-4885 (fax) +91-44-2-223-1034
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