Infectious Diseases

Parasitic Diseases

Several research groups investigate the molecular and immunological correlates of parasitic infection. In Cape Town, the Cytokines and Disease Group (Brombacher) aims at elucidating the fundamental immunological mechanisms underlying human diseases, such as tuberculosis, African trypanosomiasis, leishmaniasis, helminthic infections (including bilharzia) and the role of neuroimmunology, in addition to chronic diseases like allergic asthma and colitis. In New Delhi, six Groups investigate the malaria parasite. The Malaria Biology (Malhotra) and the Parasite Cell Biology (Mohmmed) Groups functionally characterize proteins encoded by the malaria parasite that could become targets for the development of innovative antimalarial drugs or become vaccine candidates. The Parasite Biology Group (Tuteja) studies the Plasmodium proteins involved in the maintenance of parasite genomic integrity, while the Malaria Drug Discovery Group (Sahal) investigates the antimalarial properties of molecules isolated from marine organisms, medicinal plants, cyanobacteria and endophytic fungi from India and other sources in Africa and Asia. The Structural Parasitology Group (Sharma) uses a structural approach aiming to define the principles governing the biological functions of key malaria proteins, particularly focusing on the protein translational machinery of the parasite. The Transcriptional Regulation Group (Bhavesh) has a broad interest in elucidating the molecular interactions between protein and RNA involved in post-transcription regulation of mRNA, which it addresses by a combination of NMR spectroscopy and crystallography.

Highlights

The Cytokines and Disease Group in Cape Town has contributed some major advances of our understanding of helminth infection, allergic responses  and neuroimmunology on the immune responses affecting inflammation. In schistosomiasis we  worked on antiparasitic drugs and preclinical models in humans (Nono et al, 2020, Scientific  Report;  Kamdem et al, 2020, Scientific  Report). Indeed, worm infections can also impact on neuro-immunology (Brombacher et al, 2020, Brain  Behav Immun SO889) and memory (Brombacher et al, 2020, Scientific  Reports). Allergic reaction are also top priorities with new insights on the role of B cells (Hadebe et al, 2020 J. Allergy Clin Immunol 28:889) and T regulatory cells, which  restain airway inflammation via limiting local tissue IL-33 (Khumalo et al, 2020, JCI Insights, e 136206), The Malaria Biology and Parasite Cell Biology Groups in New Delhi have made important advances in understanding novel protein complexes on the malaria parasite surface and their post translation modification which play a key role in the invasion of red blood cells (Ekka et al., mBio. 2020, 11(5):e00166-20. Chourasia et al., 2020 Infect Immun.;88(2), thereby opening novel ways of potentially blocking parasite infection. Based upon their discovery of coalesced pathways of haemoglobin degradation and hemozoin formation (Chugh et al., 2013, Proc Natl Acad Sci;110(14):5392-7.), they have developed highly potent novel parasiticidal compounds with high potential to be developed as new antimalarials (PCT Int. Appl. (2019), WO 2019202609 A1 20191024; Indian Pat. Appl. (2019), IN 201811014401 A 20191018.; Aratikatla et al., ACS Omega. 2020, 5(45):29025-29037. Rana et al., 2020, Bioorg Med Chem.;28(1):115155). Studies from the Structural Parasitology Group in New Delhi identified novel hit compounds targeting parasite tRNA synthetases and structural basis on the inhibitory activities (Sharma et al., Nat Commun. 2021,12(1):343; Baragaña B. et al., Proc Natl Acad Sci 2019;116(14):7015-7020; Mishra e al., Acta Crystallogr. 2019; 75(Pt 11):714-724). Transcription Regulation group identified novel structural states of Chaperone YadV (Pandey et al., FEBS Lett. 2020,594(18):3057-3066).