Research Groups

Mammalian Biology: Malaria

Research Interests and Description

Staff Research Scientist: Pawan Malhotra

Research Interests

Plasmodium secretory proteins, Merozoite Surface Protein-1, PfRhopH3, Falcipain-2, a malaria cysteine protease, PfSel1 and PfSel2 proteins.

Description of Research

Identification of protein complexes [ligand complex(s)] on the surface of merozoites, the invasive form of malaria parasites at asexual blood stages of P. falciparum
Using complementary approaches, such as bacterial two hybrid analysis, in vitro interaction study and immunoprecipitation analysis, we have identified a molecular interaction between a major Plasmodium surface protein, Merozoite surface protein-1 and a rhoptry secreted protein, PfRhopH3 that is part of a high molecular weight rhoptry protein complex, referred as PfRhopH complex. Mass spectrometry based proteomic analysis of anti-PfMSP-1 and anti-PfRhopH3 immunoprecipitates revealed stable association of eight parasite surface proteins, PfMSP-3, PfMSP-7, PfRhopH1, PfRhopH3, PfRAP-1, PfRAP-2 and two putative PfRhoptry associated proteins with PfMSP-1. Presently, we are attempting to functionally characterize the PfMSP-1 associated complex. In addition, we have also isolated a hemazoin-associated protein complex from P. falciparum and work is in progress to learn the determinants of this complex.

Analysis of extracellular secretory antigens at asexual blood stages of P. falciparum
Recently, the Group successfully carried-out proteome analysis of P. falciparum extracellular secretory antigens using two complementary approaches, two dimensional gel electrophoresis/MS and LC-MS/MS. The study revealed a cohort of proteins with possible role(s) in immune evasion. Of these antigens, preliminary functional characterization data of two novel (Sel1 repeat-containing) parasite proteins, PfSel1 and PfSel2 revealed that they down-regulate expression of cell surface Notch signaling molecules in host cells. Currently work is in progress to express other extracellular antigens and look at their immune-modulation potential.

Identification of regulatory small RNA species in P. falciparum
We have generated small RNA libraries from different asexual blood stages of P. falciparum. Work is underway to identify the small RNA species and understand their role(s) if any in parasite development.

Recent Publications

Singh, M., Mukherjee, P., Narayanasamy, K., Arora, R., Sen, S., Gupta, S., Natarajan, K., Malhotra, P. 2009. Proteome analysis of Plasmodium falciparum extracellular secretory antigens at asexual blood stages reveals a cohort of proteins with possible roles in immune modulation and signaling. Mol. Cell. Proteomics 8, 2102-2118

Gupta, S., Salam, N., Srivastva, V., Singla, R., Behera, D., Khayyam, K.U., Korde, R., Malhotra, P., Saxena, R., Natrajan, K. 2009. Voltage gated Calcium channels negatively regulate protective immunity to Mycobacterium tuberculosi. PLoS One 494, e5305

Singh, G., Popli, S., Hari, Y., Malhotra, P., Mukherjee, S.K., Bhatnagar, R.K. 2009. Suppression of RNA silencing by Flock House Virus B2 protein is mediated through its interaction with PAZ domain of Dicer. FASEB J. 23, 1845-1857

Varshney, A.K., Chaudhry, R., Saharan, S., Kabra, S.K., Dhawan, V., Dar, L., Malhotra, P. 2009. Association of Mycoplasma pneumoniae and Asthma among Indian patients. FEMS Immunol Clinical Microbiol. 56, 25-31

Reed, Z.H., Kieny, M.P., Engers, H., Fried, M., Chang, S., Longacre, S., Malhotra, P., Pan, W., Long, C. 2009. Comparison of immunogenicity of five MSP-1 based malaria vaccine candidate antigens in rabbit. Vaccine 27, 1651-1660