Research Groups
Mammalian Biology: Malaria
Research Interests and Description
Research Interests
Characterization of P. falciparum proteins as novel drug targets and vaccine candidates; understanding the basic biology of red cell invasion and cytoadherence by malaria parasites and development of malaria vaccine candidate antigens for clinical trials.Description of Research
Malaria immunity and vaccine research
Development of combination malaria vaccines for both P. falciprum and P. vivax, based on the major merozaite surface proteins, responsible for protective immune responses in the host. Development of chimeric immunogens based on immunologically relevant regions of blood stage malaric antigens. A chimeric protein based of Pf MSP-3 and the C-terminal fragment of Pf MSP-1 has showed good promise in animal models. Immunisation in small animals has shown that the two components in the fusion protein have retained their structural and immunological integrity. Protocols for preparing the fusion protein at laboratory scale have been developed. In collaboration with Dr. Chitnis, we are establishing an expanded malaric vaccine program which should enable us to take at least three experimental vaccines to clinical trials. This expanded program is expected to be supported by a few national and international funding agencies.
Malaric Drug Research
Along with Dr. Sahal, the Group has established High Throughput Screening methods developed at ICGEB and we are currently investigating antimalarial activity of compounds from the plant and marine sources. We are also using proteomics based approach to investigate the mechanism of action of antimalarial drug, artemisnin.
Synthethic peptides as immunogens, peptidomemetics drugs and self assembling systems
We have an ongoing program on design and synthesis of conformationally restricted peptides containing non-protein amino acids which can stabilize β-turns and helical structures in model peptides. More recently we have used these design principles in:
a) The design of medium sized helical, basic peptides as novel antibiotics, some of these peptides show activity in low micro molar range and have potential to move to the development stage, in collaboration with pharma industry. We are developing small peptides as anti-fibrilizing agents.
b) Synthesis characterization and anti-fibrilizing activity have been investigated and these small peptides will now be studied for their potential as anti-Alzheimer and anti type2-diabetes molecules in suitable animal models.
c) Small peptides have been characterized to show remarkable properties as self assembling system giving rise to nano sized structures with tunable functional properties. We have utilized natural and modified amino acids as basic building blocks and synthesized small peptides that self assemble in nanotubular, nano vesicular and as hydrogel structures. These self assembled structures are highly stable in different conditions and to proteolytic degradation. These biodegradable nanostructures are being investigated as delivery vehicles for drug like molecules, modified immunogens and as matrix for three dimensional cell growth.
Designing Synthetic Immunogenes for neutralizing antibodies against HIV
In a separate programe, supported by the International Aids Vaccine Initiative (IAVI) and the Department of Biotechnology, we are developing conformationally restricted peptides based on the major B-cell epitopes from the gp41 protein of the HIV. Several peptides ranging from 14 to 25 residues are being synthesized, and will be tested in their potential for providing viral neutralizing antibodies.
Recent Publications
Mayor, A., Rovira-Vallbona, E., Srivastava, A., Sharma, S.K., Pati, S.S., Puyol, L., Quinto, L., Bassat, Q., Machevo, S., Mandomando, I., Chauhan, V.S., Alonso, P.L., Chitnis, C.E. 2009. Functional and immunological characterization of a Duffy binding-like alpha domain from Plasmodium falciparum erythrocyte membrane protein 1 that mediates resetting. Infect. Immun. 77, 3857-3863
Gangwar, D., Kalita, M.K., Gupta, D., Chauhan, V.S., Mohmmed, A. 2009. A systematic classification of Plasmodium falciparum P-loop NTPases: structural and functional correlation. Malar J. 18, 69
Wickramarachchi, T., Cabrera, A.L., Sinha, D., Dhawan, S., Chandran, T., Devi, Y.S., Kono, M., Spielmann, T., Gilberger, T.W., Chauhan, V.S., Mohmmed, A. 2009 A novel Plasmodium falciparum erythrocyte binding protein associated with the merozoite surface, PfDBLMSP, Int J Parasitol. 39, 763-773
Gupta, M., Acharaya, R., Ramakumar S., Ahmed F., Chauhan V. S. 2008.
Dehydrophenylalanine (ΔPhe) as a β-breaker: Extended structure
terminated by ΔPhe induced turn in the pentapeptide
Boc-Phe1-Ala2-Ile3-ΔPhe4-Ala5-OMe. ChemBiochem,9, 1375-1378
Panda, J.J., Mishra, A., Basu, A., Chauhan, V.S. 2008. Stimuli Responsive Self-assembled Hydrogel of a Low Molecular Weight Free Dipeptide With Potential for Tunable Drug Delivery. Biomacromolecules 9, 2244-2250
Madhvi, G., Rudresh, A., Mishra, S., Ramakumar, A., Faizan, Chauhan, V.S. 2008. Design, synthesis and characterization of dehydrophenylalanine containing peptide as anti-fibrillization agents for possible use against Alzheimer’s disease. Chembiochem 9, 1375-1379
