WEHI Wednesday Seminar hosted by Professor Guillaume Lessene
 

Dr Brad Sleebs

Laboratory Head – New Medicines & Diagnostics division, WEHI

Probing for antimalarial drug targets – the old and the new

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

Malaria, caused by the Plasmodium parasite, remains a serious global health threat. The emergence of drug resistance raises concerns that the current arsenal of clinically approved artemisinin-based combination therapies and experimental drug candidates may not be sufficient for disease elimination. This highlights the urgent need to continuously develop new antimalarial compounds to strengthen the clinical portfolio. To support the global effort to treat and eliminate malaria, we screened libraries of drug-like small molecules against the asexual stage of P. falciparum, identifying hit classes with diverse and unique chemical scaffolds. These hit classes demonstrated potent anti-plasmodial activity without exhibiting cytotoxic effects on human cell lines, making them promising candidates for antimalarial development. This presentation explores the optimisation and characterisation of multistage antimalarial activity while investigating the mechanisms of action of two exemplar hit classes. Through forward genetics, we identified the molecular targets of these novel antimalarials, which were validated via cross-resistance assays and reverse genetics. The optimised compounds displayed multistage efficacy in vitro and showed effectiveness in mosquito transmission models and asexual mouse models, underscoring their potential as multistage antimalarial therapies.

Dr Sleebs is a Laboratory Head in the New Medicines and Diagnostics Division at the Walter and Eliza Hall Institute. His past research includes the development of anxiolytics in collaboration with Bionomics and agents that target the BH3 family of proteins for the treatment of blood cancers in collaboration with Genentech and AbbVie. His current research focuses on developing small molecule probes to better understand biological processes that are essential to the survival of parasites that impact both human and animal health. In parallel, Dr Sleebs leads drug discovery programs to design new therapeutics to treat parasitic diseases in collaboration with academic and industry partners, including Janssen Pharmaceuticals, Medicines for Malaria Venture and MSD.

All welcome!