Research

Inter-Disciplinary Research

Protozoan parasites, such as those responsible for malaria and African Sleeping Sickness, represent a huge burden to the developing world. Dr Karen Grant, Lancaster Medical School, is involved in ongoing collaborative research which integrates biology and chemistry in the search for new drugs against two important protozoan parasites, Leishmania and Trypanosoma, the infective agents in leishmaniasis and African sleeping sickness respectively.

Dr Grant's work validated a leishmanial cyclin-dependent kinase (CDK), CRK3, as a potential drug target in Leishmania and identified CDK inhibitors with anti-parasite activity in vitro. Optimisation of CRK3 inhibitors is ongoing in collaboration with Dr Nick Westwood at the University of St Andrews and Prof Malcolm Walkinshaw at the University of Edinburgh using a variety of different approaches, including classical chemical derivatisation and model-based rational drug design.

Dr Grant is also involved in a multi-centred collaborative project which integrates chemistry and biology and links academia (Universities of Lancaster, Glasgow, Edinburgh and Manchester) and industry (the biopharmaceutical company, Cyclacel). It aims to use a number of different approaches to discover, design or develop small molecule inhibitors of CRK3 from the 2 parasitic protozoa: Leishmania (leishmaniasis) and T.brucei (African sleeping sickness), with the view to develop a novel chemotherapy which would treat both of these important parasite diseases.

This work was funded by the Medical Research Council.

 

Contact LMS

Lancaster Medical School
Furness College
Lancaster University
Lancaster
LA1 4YG
United Kingdom

Tel: +44 (0)1524 594547


Model of CRK3 in comparison to human CDK2

Model of CRK3 in comparison to human CDK2: Overlay of the crystal structure of human CDK2/cyclin A (PDB ID: 1E9H) with the model of CRK3.
The amino acid side chains of CDK2 are in grey and those of CRK3 in purple. Indirubin-5-sulfonate is bound into the ATP-binding site of CDK2/cyclin A.

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