Malaria
and Other Parasitic Diseases |
 |
|
Focus
on Malaria, Leishmania
and Filaria
|
| |
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 and 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, structure and molecular modelling for drug design, 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 of interest. |
|
|
| |
| 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: |
• |
Malaria
- |
• Plasmodium falciparum (sensitive and resistant strains) erythrocytic stage in vitro; liver stage 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
|
• |
Leishmania:
- |
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 /Balb/c
models
|
• |
Filaria |
• Brugia
malayi motility and MTT reduction
in vitro
•
Brugia malayi infection in rodent
models Mastomys /couchal Jirds.
|
|
|
| Exploration of Novel Drug Targets |
|
• |
Characterization of unique biochemical pathways and enzymes for identification and validation of putative drug targets in Plasmodium, Leishmania and Brugia malayi. |
• |
Elucidation of mechanism of drug resistance and development of targets for rational designing of new antileishmanials and antifilarials. |
|
| |
| Molecular
and Cell Biology of Parasites |
|
• |
Delineation of the mechanism of DNA replication and translation of the P. falciparum apicoplast genome. |
• |
Molecular characterization of proteins involved in the SUF pathway of [Fe-S] biogenesis in the apicoplast. |
• |
Generation of regular or conditional mutants in Plasmodium berghei for the functional characterization of Plasmodium proteins |
• |
Addressing the role of DNA quadruplexes in Plasmodium gene regulation |
• |
Investigating mechanism of drug action of promising anti-leishmanial agents |
• |
Actin network proteins and their function in Leishmania |
• |
Characterization of chaperonins in Leishmania and their interacting partners. |
• |
• Molecular and biochemical characterization of MAP Kinase1 in Leishmania, role in resistance and posttranslation modification of proteins |
• |
• Molecular characterization of Wolbachia transcription elongation factor (Wol GreA) and translation initiation factor 1 (Wol Tl IF-1). |
• |
Structural modeling and inhibitor identification using in silico and rational approaches. |
|
| |
| Identification
and Validation of Parasite Vaccine Target
Molecules: Their Prophylactic Potential against
Leishmania and Filaria |
|
• |
Leishmania: Th1 stimulatory proteins and their peptides |
• |
Filaria: B. malayi and Wolbachia proteins as multisubunit and DNA vaccine |
|
| |
| Immunobiology |
|
• |
Wolbachia - Immunological characterization of recombinant Wolbachia surface protein (WSP). |
• |
Elucidating the immune evasion strategies adopted by the filarial parasite B. malayi at the earliest host-parasite interface. |
• |
Identification and characterization of genes involved in the pathogenesis of Tropical Pulmonary Eosinophilia (TPE), a rare but fatal manifestation of Filariasis. |
• |
Recombinant expression of cytokine homologues of B. malayi and immunological characterization of recombinant Wolbachia surface protein (WSP). |
|
|
| |
| |
| |
| |
