Sleebs Lab

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: Trent Ashton, William Nguyen, Madeline Dans, Kyle Awalt, Wenyin Su, Petar Calic, Mahta Mansouri.

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

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 and the closely related cryptosporidium parasite. Our team is currently developing these small molecule classes as potential therapeutics to treat malaria and cryptosporidiosis.

Team members: William Nguyen, Madeline Dans, Wenyin Su

Collaborators: Alan Cowman, Chris Tonkin, Kym Lowes and an industry partner

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, Lydia Scott, Sayali Shah, Petar Calic, Mahta Mansouri.

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

Parasitic worms (helminths) infect 50% of the human population and represent a major socioeconomic burden i due to the helminthiases that they cause in agriculture. Treatment failures and evidence of anthelmintic resistance are limiting treatment options, such that there is an unmet need for new treatment strategies.

Using molecular techniques and high throughout put screening, we have identified multiple small molecule classes with nematicide activity. Our aim is to use medicinal chemistry methods to optimise potency of these small molecules to achieve improve efficacy against nematode worms in vitro and ultimately in mouse models. A secondary aim is to use genomic and proteomic methods to understand the mechanism by which the small molecules under development kill nematodes.

Team members: Nghi Nguyen, Harrison Shanley

Collaborators: External collaborators and a industry partner