University of Durham

Start : December 2011 | Status : Complete

The scientists: Jennifer Norcliffe, MSci graduate in Natural Sciences (Biology and Chemistry) and currently pursuing a PhD at Durham University and John Mina, PhD in Chemical Biology were the visiting researchers from Durham University where they worked in a team led by Drs Paul Denny (Senior Lecturer in Parasitology) and Patrick Steel (Senior Lecturer in Chemistry) at the Biophysical Sciences Institute laboratories in the Department of Chemistry at Durham University

The sponsor: Durham University is England’s third oldest university based at a UNESCO World Heritage Site that is jointly owned with Durham Cathedral. It is a world top 100 university with a global reputation and performance in research and education. The Department of Chemistry at Durham is one of the UK leading centres for chemical sciences and has a long tradition of interdisciplinary research. It is an integral component of the Biophysical Sciences Institute.

Foundation funding: The Foundation provided £61,555.

GlaxoSmithKline’s contribution: GSK provided in-kind contributions (including facilities and expertise from supporting scientists for HTS and GSK collection of compounds).

Project Description: 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).