Principal Investigator (PI)
The Foundation is providing £61,555 in support.
Jennifer Norcliffe - John Mina
GSK provided in-kind contributions (including facilities and expertise from supporting scientists for HTS and GSK collection of compounds).
Leishmaniasis, Chagas Disease and Human African Trypanosomiasis (African sleeping sickness) are neglected tropical diseases caused by infections spread by kinetoplastid parasites. All are potentially fatal but treatments are expensive and not widely available. Emerging resistance is also a problem and therefore new and inexpensive therapeutic treatments are urgently needed
Supported by GSK scientists specialised in screening and compound profiling, John and Jennifer used the automated screening equipment and GSK’s extensive compound library to design and run a high-throughput yeast-based assay in order to identify inhibitors of the target enzyme in the kinetoplastid parasite that could be a target for new treatments.
This research helped identify 500 compounds that displayed a high degree of activity against relevant enzymes. From the 500 compounds identified by screening, 216 have been selected for further investigation. This next stage of research includes both biochemical screening and activity determination against both insect-stage and host-stage parasites. The most promising hits will be subjected to further tests in order for the best lead-like candidate to be produced.
“GSK’s involvement has been vital in moving this project forward. It would have been impossible to undertake a screen of this magnitude without the specialised equipment they supplied.
The provision of GSK’s own compound library has enabled us to identify a much larger number of diverse chemical entities than we would otherwise been able to discover, increasing our chances of identifying and developing suitable lead-like compounds in the future.
As an academic institution, access to a compound library of this size and equipment capable of ultra-high-throughput screening is unprecedented. The Tres Cantos Open Lab Foundation also afforded our group the opportunity to undertake work that would be difficult to fund through conventional mechanisms such as Research Councils UK. On a personal level, at such an early career stage it was an incredible opportunity to acquire new skills and to work alongside and learn from industry experts” (Jennifer Norcliffe, Open Lab scientist).