Defining the role of RNA metabolic processes in colorectal cancer development

This is one of several projects available on a CRUK funded PhD programme at the Cancer Research UK Edinburgh Centre, which is part of the Institute of Genetics and Molecular Medicine (IGMM) at the University of Edinburgh.

Project details

Colorectal cancer is the second commonest cause of cancer related mortality and there is a pressing unmet need for new therapies for its treatment. Current therapeutic options for colorectal cancer treatment include so called ‘targeted therapies’ that act against specific molecular alterations present in tumours. These treatments work extremely well against their molecular targets but resistance to them routinely develops and patients have limited survival benefit. One possible explanation is that as these therapies only target a single molecular aberration it is relatively simple for tumours to bypass the requirement for the target, possibly via activation of alternative tumour promoting mechanisms. Work in our lab is aimed at understanding the mechanisms for this and defining other potential targets for therapeutic development.

Previous work in the lab has identified core cellular processes involved in multiple stages of RNA metabolism (RNA splicing, tRNA metabolism and rRNA metabolism) as being highly activated in colorectal cancer tissue. We have investigated the role of RNA splicing in colorectal cancer and discovered that tumour cells are highly dependent on the RNA splicing machinery to survive and proliferate. Interestingly, normal tissue is much more tolerant to depletion of RNA splicing indicating that the inhibition of this process could have potentially therapeutic benefits. As RNA splicing is an important cellular process the development of resistance mechanisms will likely be less problematic.

This PhD project will extend this analysis to the function of tRNA and rRNA metabolism in colorectal cancer. Using a combination of a state-of-the-art CRISPR/Cas9 organoid screening system developed in the lab, in vivo colorectal cancer models, and tumour histology we will determine whether colorectal cancer cells are more susceptible to depletion of components of these cellular processes than normal cells. This will potentially define novel cellular processes driving colorectal cancer and open new therapeutically exploitable opportunities.

For further information on how to apply for this project, please visit: https://www.ed.ac.uk/cancer-centre/study-with-us/cancer-research-uk-phd-programme