Brad Sleebs-Projects

Brad Sleebs-Projects

Researcher: 

Projects

Design of novel antimalarial agents

Malaria is a devastating disease that results in 460,000 deaths annually. Our laboratory is contributing to the global effort to develop novel small molecule therapies to treat and eliminate malaria.

Our team is currently optimising several small molecule classes identified from phenotypic screening of the malaria parasite. The antimalarial classes exert differential activity against multiple stages of the parasite’s lifecycle and therefore have potential as a prophylactic, a curative therapy or being used to eliminate malaria from endemic regions.

We are also employing chemical biology and genetic techniques to identify the mechanism of action of the small molecule classes under development.

Team members: William Nguyen, Trent Ashton, Madeline Dans, Brodie Bailey, Wenyin Su

Collaborators: Alan Cowman, Kym Lowes, external collaborators and industry partners

Targeting aspartyl proteases in the malaria parasite

The malaria parasite encodes ten cathepsin D-like and one viral aspartyl protease. Our laboratory is focused on developing small molecule tools and developing genetic models to help understand the essential role of these aspartyl proteases in malaria parasite survival. This research has established the essentiality of several malaria aspartyl proteases and therefore suggesting these are attractive antimalarial drug targets.

In the next phase of our research, we have identified drug-like starting points independently targeting several essential aspartyl proteases of the malaria parasite.

Our team is currently developing these small molecule classes as potential therapeutics to treat malaria.

Team members: William Nguyen, Madeline Dans, Wenyin Su, Brodie Bailey

Collaborators: Alan Cowman, Justin Boddey, Kym Lowes and an industry partner

Targeting SH2 domain proteins as a novel immune oncology therapy

Natural killer (NK) cells have emerged as a potential target in the innate immune system as they are highly toxic to tumor cells.

Interleukin 15 (IL-15) is an essential regulator and activator of NK cells. Our institute has discovered a novel checkpoint protein, CIS (cytokine-inducible SH2-containing protein), enhances NK cell response to IL-15 and thus NK cell activity. CIS is a member of the Suppressor of Cytokine Signaling (SOCS) family and negatively regulates IL-15-mediated NK cell proliferation, and therefore inhibiting CIS is a strategy to activate NK cell populations to destroy tumor cells. Our team is currently developing small molecule inhibitors of CIS as a potential immune-oncotherapy.

 

Team members: Nghi Nguyen, Iain Currie, Trent Ashton, Lydia Scott, Hao Chen

Collaborators: Sandra Nicholson, Jeff Babon, Kym Lowes and an industry partner

Development of small molecules for the treatment of nematode diseases

This project aims to establish an advanced, industry-linked pipeline for the development of new drugs against nematodes that cause serious diseases in humans and agricultural livestock. The project is geared towards developing new small molecule therapies to treat nematode diseases, and expects to discover new ways of killing parasites that survive in their host, despite being under severe attack by the host immune system.

 

Team members: Nghi Nguyen, Harrison Shanley

 

Collaborators: Gasser lab, University of Melbourne and an industry partner