Research Fellows Directory
Dr Claire Eyers
University of Manchester
The addition of phosphate groups to proteins regulates their function in all cells. This fundamental regulatory process, termed phosphorylation, is used by human cells to respond to a multitude of changes in their cellular environment, and an excess or absence of protein phosphorylation is the cause or consequence of many disease states, including cancer and diabetes. Phosphorylation is a reversible modification and addition of phosphate is regulated by a large family of enzymes termed protein kinases, of which there are over 500 in humans. Excitingly, many of these enzymes are key therapeutic targets for drug discovery, and this group of proteins have become the second most important group of drug targets for the treatment of human diseases. An understanding of protein kinase regulation is therefore critical for a detailed understanding of human biology and disease.
I am using recent advances in the field of quantitative mass spectrometry (a powerful technique used to analyse molecules based on their mass-to-charge ratio) to measure the absolute amounts of specific proteins in defined ‘signal transduction’ cascades. I have also developed methodology that can be used to determine the precise amount of the modified forms of these proteins. This information is being used to enhance mathematical models of these systems in human cells. Perturbation of these systems, for example by using small molecule therapeutics can then be assessed in the absence of traditional biological experiments. The rate at which small molecule therapeutics have become effective therapies for the treatment of disease has reduced significantly in recent years, primarily because of failure to produce a significant effect in whole animal models (lack of efficacy), or toxicity effects. The quantitative systems biology studies that I am performing will enable computational analysis of the optimum point(s) at which these pathways should be targeted to maximise drug efficacy and minimise toxicity.