School of Infection & Immunity

Professor Chris Tonkin

  • Associate Professor (The Walter and Eliza Hall Institute of Medical Research)
  • Location: C222, BHF Building and Zoom

Zoom link: https://uofglasgow.zoom.us/j/85762296083?pwd=vRWgkq9yvQPUpZSL51hkAbr0GpStMH.1

Passcode: 513825

Title: Targeting Aspartyl Proteases to treat Cryptosporidiosis

Synopsis: 

Cryptosporidiosis, caused by Cryptosporidium spp., has one sub-optimal treatment option, despite being a leading cause of childhood diarrheal morbidity and mortality. As part of a 10 year collaboration Merck Sharp Dohme (MSD),  and WEHI generated over 5,000 compounds that target aspartyl proteases. We screened our Aspartyl Protease Inhibitor Library (APIL) against Cryptosporidium and found a collection of highly potent inhibitors. We identified the ASP4 in Cryptosporidium targeted by these compounds,  7% of which has EC50s as < 20nM. Hits were then optimised for both intestinal restriction and on-target specificity, resulting a lead with an IC50 in the picomolar ranges and significantly improved clearance in mouse animal models. Using these compounds, we show that CpASP4 is required for export of newly identified effector proteins, cleaving at a defined motif that enables export. This compound is not only the beginning of a new exciting drug program but also provides the field with a new tool compound to understand host pathogen interactions.

Bio:

Chris Tonkin has a long standing interest in understanding the molecular basis of pathogenesis in apicomplexan parasites having worked across Plasmodium, Toxoplasma and more recently Cryptosporidium. Throughout his career Chris has worked on protein trafficking the the relict plastid (apicoplast), antigenic variation in Plasmodium, motility and invasion as well as protein export and host cell manipulation. Chris is currently head of the Division of Infection and Global Health at The Walter and Eliza Hall Institute of Medical Research (WEHI), in Melbourne Australia.

First published: 12 May 2026

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