Infectious Diseases

Parasitic Diseases

Several research Groups investigate the molecular and immunological correlates of parasitic infection. In Cape Town, the Cytokines and Disease 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 and helminthic infections (including bilharzia), in addition to chronic diseases like allergic asthma and colitis. In New Delhi, five Groups investigate the malaria parasite. The Malaria Biology (Malhotra) and the Parasite Cell Biology (Mohmmed) Groups search for 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, which it addresses by a combination of NMR spectroscopy and crystallography.

Highlights

The Cytokines and Disease Group in Cape Town has major advances in our understanding of how the immune response affects inflammation following helminth infection, and has defined a specific role for interleukin-4Rα in a specific subset of T cells, as being essential for controlling the immune response and minimising the disease pathology (Abdel Aziz et al., 2018, PLoS Biol., 16, e2005850). The Group also published an important review on the potential novel use of statins, normally used to treat cardiovascular disease, which can potentially be repurposed as adjuncts to treat a variety of infectious diseases (Parihar et al., 2019, Nat. Rev. Immunol., 19, 104–117). 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 which play a key role in the invasion of red blood cells (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.), the Group 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.; 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. (Chhibber-Goel, J., and Sharma A. Proteins. 2019; 87(9):730-737; Baragaña B. et al., Proc Natl Acad Sci 2019;116(14):7015-7020; Mishra e al., Acta Crystallogr. 2019; 75(Pt 11):714-724).