Malaria
and Other Parasitic Diseases |
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focus
on Malaria, Leishmania
and Filaria
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With
prevalence in more than a 100 countries
and more than 4 billion people worldwide
at combined risk, diseases caused by these
three parasites represent a major biomedical
challenge. Researchers at the institute
address issues pertaining to design and
development of novel drug molecules as well
as optimization and preclinical development
of lead molecules & combination therapy
regimens, besides investigation of novel
drug delivery systems. A significant basic
research component of the programme focuses
on identification and characterization of
novel drug targets, understanding mechanisms
of drug action and drug resistance, investigation
of aspects of parasite biology and host-parasite
interaction, immunoprophylaxis and immunodiagnosis.
The contribution of host genetic factors
in malaria susceptibility in Indian populations
is also under investigation. The structural
biology component of the programme aids
in molecular modeling and X-ray structure
determination. |
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| Drug
Discovery & Development |
Synthesis
of compounds for anti-parasitic activity
based on identified leads for rational drug
design as well as isolation from natural
products. |
Bioevaluation
against internationally
accepted in vitro and in vivo
experimental models as below: |
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Malaria
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Plasmodium falciparum
strains in vitro;
•Rodent
malaria parasites Plsmodium
yoelii (N-67 & MDR
strains), P.berghei (NK65,
ANKA strains), P. vinckeii
(sensitive and arteether resistant
strains).
•Simian
malaria parasites P.cynomolgi
and P.knowlesi
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Leishmania:
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In vitro screening assays based
on reporter genes (luciferase/Green
Fluorescent protein) are in use
for antileishmanial screening.
•Leishmania
donovani –Amastigote macrophage
model
•L. donovani
–Golden Hamster /Swiss mice
models
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Filaria |
• Brugia
malayi motility and MTT reduction
in vitro
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Brugia malayi infection in rodent
models Mastomys / Jirds.
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| Identification
and Characterization of Novel Drug Targets |
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Exploration
of unique biochemical pathways and enzymes
for identification and validation of
putative drug targets in Plasmodium,
Leishmania and Brugia malayi. |
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Elucidation
of mechanism of drug resistance and
development of targets for rational
designing of new antileishmanials using
proteomic and genomic tools. |
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| Molecular
and Cell Biology of Parasites |
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Organization
and replication of P. falciparum apicoplast
genome. |
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Molecular
characterization of proteins involved
in the transport of nuclear-encoded
proteins to the apicoplast. |
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Identification
of interacting partners of PfHsp70-1
among various DnaJ homologs annotated
in the P. falciparum genome. |
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Actin
network proteins and their function
in Leishmania. |
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Structural
modeling and inhibitor identification
using in silico and rational approaches. |
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| Identification
and Validation of Parasite Vaccine Target
Molecules: Their Prophylactic Potential against
Leishmania and Filaria |
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Leishmania:
Live attenuated parasites, Th1 stimulatory
proteins and proteophosphoglycans |
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Filaria:
B. malayi RNA helicase, heavy chain
myosin and mitochondrial fraction and
sub-fraction |
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| Immunobiology |
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Wolbachia
- Brugia malayi – host interaction
and molecular characterization of selected
proteins with altered expression in
2D gel post-Wolbachia depletion. |
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In vitro
cross-talk between immune cells - B.
malayi – Wolbachia |
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Cloning
and characterization of filarial diagnostic
antigen |
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Purification
and characterization of pro-inflammatory
and anti-inflammatory molecules of B.
malayi. |
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Characterization
of Th1/Th2 type of immune responses
following different routes of infection
and post Miltefosine treatment. |
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