Malaria Biology

INFECTIOUS DISEASES / Parasitic Diseases

Research Interests

Understanding malaria parasites biology with an aim to identify new drug and vaccine candidate antigens.

Description of Research

Food Vacuole- Target for new drug discovery against malaria parasite
Our Group has been working on illustration of P. falciparum food vacuole proteome to understand process of hemoglobin degradation as well as to know the proteins that are involved in resistance to current antimalarials.  In 2013, we identified a ~200kDa protein complex consisting of falcipain2/2’, plasmepsin II, plasmepsin IV, histo aspartic protease and Heme Detoxification protein (HDP) inside the food vacuole that is involved in hemoglobin (Hb) degradation and hemozoin (Hz) formation. Using recombinant PfHDP and falcipain-2, we developed an in vitro Hb degradation and Hz formation assay. Further using in silico and biochemical approaches, we characterized PfHDP for heme binding as well as hemoglobin binding sites. Screening of compounds from Maybridge Screening Collection that bound the modeled PfHDP structure, identified a compound that inhibited parasite growth in a dose dependent manner, thus paving the way for testing its potential as a new drug candidate. Presently, we are working on this scaffold by computational, structural and experimental approaches for rational drug design to combat drug resistant malaria.

Using proteome approaches, we have recently identified a number of transporters that show frame-shift or missense mutations in resistance field isolates. In collaboration with Dr Asif Mohmmed and Dr Inderjeet Kaur, we are presently developing CRISPR-CAS9 tools to understand the functional relevance of these mutations.

Novel host-parasite interactions involved in Plasmodium falciparum invasion of human RBCs
More than 50 surface antigens are expressed on Plasmodium merozoite surface, however till date ten possible interactions between these antigens and their respective receptors on human RBCs have been characterized. Our group along with other colleagues has recently described two novel erythrocyte receptors; Intercellular Adhesion Molecule 4 (ICAM4) and Cyclophilin B that seem to play important role(s) at different steps of merozoite invasion of human RBCs. Presently work is on to identify novel inhibitor(s), which can block these interactions and possibly the invasion.

Proteome analysis to identify novel protein complexes on Plasmodium merozoite surface and to identify pathways/proteins that are regulated by post-translation modifications
We have been applying proteome-based approaches to illustrate protein complexes on Plasmodium merozoite surface and also to identify pathways/proteins that undergo post-translational modifications. In this context, we have recently described a novel, 6-Cys protein complex comprising of Pfs41, Pfs38, Pfs12, GLURP, SERA5 & MSP-1 and a MSP 3 complex comprising of MSP-1, MSP-6 and MSP-7 proteins. Using liquid chromatography and tandem mass spectrometric analysis, we have first time described lysine as well as arginine methylated Plasmodium proteins at asexual blood stages. Work is on to identify the pathways that are regulated by these proteins and also to develop novel inhibitors to parasite enzymes that are responsible for methylation of parasite proteins.

The Group has recently made ground-breaking advances in understanding and characterizing a novel Plasmodium falciparum merozoite glideosome complex, and proteasome shuttle/interacting proteins, which play key roles in the invasion of red blood cells and protein homeostasis respectively (Saini, E et al., PLOS Pathogens. 2021; Onchieku et al., 2021, Pathogens), thereby opening novel ways of potentially blocking parasite infection and development.

Recent Publications