Research Groups

Molecular Medicine: Malaria Biology

Research Interests and Description

Group Leader: Pawan Malhotra, PhD

Group Members

Research Interests

Plasmodium hemoglobinases as drug targets, newer approaches to malaria vaccine development, Plasmodium cytoskeleton binding proteins

Description of Research

Hemoglobinases and Heme detoxification protein as drug targets for the development of antimalarial
We have identified a ~200kDa protein complex consisting of parasite proteases; falcipain 2/2’, falcilysin, plasmepsins II and IV, Histo Aspartic Protease (HAP), and a Heme Detoxification Protein (HDP) in Plasmodium falciparum food vacuole that degrades hemoglobin (Hb) and converts heme to hemozoin. We further showed that two current antimalarials; chloroquine and artemisinin act on this pathway. We have now functionally characterized HDP and showed that this protein has hemoglobin as well as heme binding sites. Presently small compound libraries are being screened against hemoglobinases and HDP protein to identify new inhibitors against malaria parasite.

Functional analysis of P. falciparum extracellular secretory antigens at asexual blood stages
We have identified twenty-seven novel antigens that are secreted by P. falciparum at asexual blood stages and functionally characterized one of the secretory antigen: PfDegP, as thermal and stress tolerance protein in primate malaria parasites in particularly in Plasmodium falciparum. We have characterized another P. falciparum secretory Protein;  PfCCp1 that is expressed at asexual blood stages and interacts with APCs and complement pathway proteins of human host. Additionally, we have also identified a serum albumin binding protein among these secretory proteins that probably plays an important role in transport of serum albumin inside the parasite. Characterization of this protein is in progress.

Identification of novel receptor(s) and protein complexes on Plasmodium merozoites
In our quest to identify novel receptor-ligand interactions, we identified ICAMs as novel receptor on macrophages and RBCs involved in the invasion of M. tuberculosis and Plasmodium falciparum.  Using codon shuffled synthetic libraries; we synthesized a 84 amino acid peptide ; M5 that blocks the invasion of M. tuberculosis and P. falciparum into respective host cells. In addition, group is involved in elucidating the molecular interactions among parasite proteins on the merozoite surface. We have previously described a MSP-1 associated large complex. Recently, we have established another complex of Plasmodium 6-cysproteins on merozoite surface. Functional characterization of these complexes is on going.

Recent Publications

Bhalla, K., Chugh, M., Mehrotra, S., Rathore, S., Tousif, S., Prakash Dwivedi V., Prakash, P., Kumar Samuchwal, S., Kumar, S., Kumar Singh, D., Ghanwat, S., Kumar, D., Das, G., Mohmmed, A., Malhotra, P., Ranganathan, A. 2015. Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum. Nature Communication. 6: 6049. PubMed link

Kaderi Kibria, KM., Rawat, K., Klinger, CM., Datta, G., Panchal, M., Singh, S., Rajendran, G., Kaur, I., Sharma, V., Dacks, JB., Mohmmed, A., Malhotra, P. 2015. A role for adapter protein complex 1 in protein targeting to rhoptry organelles in Plasmodium falciparum. Biochem Biophys Acta- Mol Cell Research 1854: 699-710. PubMed link

Panchal, M., Rawat, K., Kumar, G., Kibria, K.M., Singh, S., Kalamuddin, Md, Mohmmed, A., Malhotra, P., Tuteja, R. 2014. Plasmodium falciparum signal recognition paticle components and anti-parasitic effect of ivermectin in blocking nucleo-cytoplasmic shuttling. Cell Death and Diseases. 5. e 994 PubMed link

Chug, M., Sundararaman, V., Kumar, S., Reddy, V.S., Siddqui, W.A., Stuart, K.D. Malhotra, P. 2013. Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum. Proc Natl Acad Sci U S A. 110: 5392-5397. PubMed link

Ranjan, R., Chug, M., Kumar, S., Singh, S., Kanodia, S., Hossain, M.J., Korde, R., Grover, A., Dhawan, S., Chauhan, V.S., Reddy, V.S., Mohmmed, A and Malhotra, P. 2011. Proteome analysis reveals a large Merozoite Surface Protein-1 Associated Complex on the Plasmodium falciparum merozoite surface. J Prot Res. 10: 680-691. PubMed link

Singh, M., Mukherjee, P., Narayanasamy, K., Arora, R., Somdutta, 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 signalling. Molecular and Cellular Proteomics 8: 2102-2118. PubMed link

ICGEB New Delhi

ICGEB Campus
Aruna Asaf Ali Marg
110 067 New Delhi
INDIA
Tel: +91-11-26741358/1007
Fax: +91-11-26742316
icgebicgeb.res.in

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