Scheme: Wolfson Research Merit Awards
Organisation: University of Southampton
Dates: Aug 2008-Jul 2013
Summary: The synthesis of proteins is of fundamental importance to all cells, as it allows them to use their genetic information. Nearly all the jobs in cells are performed by proteins, and different kinds of cells thus contain very different sets of proteins, so their production needs to be carefully controlled. Another reason for this is that protein synthesis is very expensive for cells, using a lot of energy and nutrients. Defects in the proper control of protein synthesis can cause diseases such as cancer, neurological conditions and excessive heart growth, which can lead to heart failure. We are studying how protein synthesis is normally controlled, e.g., by hormones and nutrients, and why it is faulty in the kinds of diseases just mentioned.
Better understanding of the cellular components which cause protein synthesis to be wrongly controlled in cancer or heart disease may allow the development of new ways of treating these diseases. Furthermore, we are exploring how tumour cells adapt to the lack of nutrients they encounter due to their poor blood supply. We have identified an unusual cellular component which is necessary for them to cope with nutrient starvation, shown that blocking its function leads to death of cancer cells, and have discovered a new way it is controlled by lack of oxygen. This also opens up new avenues for cancer therapy, which we are exploring with the pharmaceutical industry.
We also study a severe inherited brain disease (vanishing white matter) which is caused by mutations in a protein that is essential for the control of protein synthesis. We are working with collaborators in Amsterdam to understand how these mutations – in a protein that is present in all cells – lead specifically to this brain disorder. In another project, we are also studying the changes in protein synthesis that play an essential role in creating new long-term memories. This involves multidisciplinary collaborations with scientists in Israel and Norway.