Completed Cells, Biochemistry & Physiology Infection & Immunity

Chemical biology: Leveraging phenotypic hits against kinetoplastids.

Funder Wellcome Charity-funded
Recipient organisation University of Dundee
Funding £2.3M
Period Jan 2015 — Jun 2020

In plain English

AI plain-English summary

Hundreds of anti-parasitic compounds sit in a chemical library, their targets inside the cells that cause sleeping sickness and Chagas disease still unknown. This matters because developing new drugs for these neglected tropical diseases has stalled. Researchers lack validated molecular targets to aim at, and they do not fully understand how the parasites survive inside human hosts. The compounds in question are already known to kill the parasites, but no one knows exactly how—which protein each one hits, or which metabolic pathway it disrupts. The team plans to build a general platform that uses genetic, cellular, chemical, and computational tools to identify each compound’s mode of action. They will then map those targets and pathways, and publish everything in a public database for other researchers to use. If this succeeds, the database will become a toolbox of high-quality chemical probes for the entire kinetoplastid research community. Drug discovery programmes, funded separately, can then use these probes to design treatments that hit validated targets, rather than screening blindly. The work is primarily fundamental science—dissecting parasite biology—but it directly feeds into the pipeline for new medicines.

View original technical description
The development of new drugs to treat kinetoplastid diseases is hampered by a lack of validated drug targets and poor understanding of parasite biology. Our vision is to develop a battery of chemical and biological tools to dissect parasite biology and validate new drug targets. Our starting point is several hundred anti-parasitic compounds, identified through phenotypic screening of compound libraries against the kinetoplastids parasites. These represent well-validated phenotypic hit compoun ds covering a broad range of structural scaffolds, suggesting that they operate through multiple distinct, although as yet unknown, modes of action (MoA). We plan to: 1. Develop a general platform for determination of the MoA(s) for anti-parasitic compounds, using genetic, cellular, chemical proteomic and computational tools. 2. Determine the MoA(s) and, where possible, the specific molecular targets for our collection of validated phenotypic hit compounds. 3. Collate chemical and biologic al MoA information on these compounds in a publically available database to provide a toolbox of high quality chemical probes to the community for investigating kinetoplastid biology. 4. Gain significant new understanding of parasite metabolic pathways and signalling mechanisms. 5. Feed the information gained into our separately funded drug discovery programmes.

View the original record at the funder ↗

Researchers

Ian Gilbert (EPMC Awardee)

Related Research

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Original classification

Strategic Award - Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.