2019 Research Grant Award
£89,349 for a 36 month PhD starting 1 October 2020 at School of Chemistry, UEA.
Dr G Richard Stephenson
Cancer is normally prevented inside healthy human cells by the presence of an important family of proteins known as Tumour Suppressor Proteins (TSPs). In previous work, we and others have identified a completely new process that causes the abnormal breakdown and disappearance of these vital TSPs, or ‘cancer brakes’. Furthermore, it has been shown that this occurs in many different types of cancer, but especially breast and prostate cancer.
This process involves a family of enzymes known as Ubiquitin Ligases which present inside cancer cells. These Ubiquitin Ligases tag the ‘cancer brakes’ for destruction by the body. We now know that these enzymes are over-produced in cancer cells that are more prone to spread around the body, and we also now understand more about how these enzymes work and, in some cases, we know their exact overall 3-dimensional shape.
In this project, we will capitalise on these key discoveries, and begin to develop new drugs targeting these ubiquitin ligase enzymes that can be used to prevent cancer outgrowth and spread. Recent developments have allowed us to identify how the drug molecules fit in the protein receptor. In the proposed period of doctoral research, the PhD Student project will make analogues of a molecule called 2805, to introduce additional binding interactions with the receptor and so provide a better series of second-generation inhibitors which can be evaluated by our recently established in-house methodologies. This information is very important as it will allow us to see which parts of the drugs are required for their activity, and which can be modified in later studies to reduce side-effects. The big advantage we have here at UEA to carry out this work is that it builds on an existing strong collaboration with experts in cancer, assay development, structural biology and chemical synthesis. The main outcomes of the project could also lead to the development of a new class of drug that could have a real impact on patient survival in the long-term.