Dr Payam Gammage, Prof Owen Sansom
The impact of cancer-associated mitochondrial DNA mutations on tumour metabolism
As a world-leading cancer research centre, the CRUK Beatson Institute supports cutting edge work into the molecular mechanisms of cancer development. We provide an outstanding research environment, underpinned by state-of-the-art core services and advanced technologies with special emphasis on imaging and in vivo models.
We are looking for students with a very good degree in a Life Sciences subject and an aptitude for experimental work, who are also highly committed to pursuing a PhD and a career in cancer research. The Beatson has an excellent reputation and success record in training its graduate students. Students, whilst being trained at the Institute working within our research groups, will matriculate with the University of Glasgow.
Our PhD studentships are for a maximum of 4 years, and currently provide students with an annual stipend of £19,000 and matriculation fees for home, EU or overseas students.
All cancers bear somatic mutations within their genomes. The contribution of these mutations in the context of DNA contained within the nucleus is increasingly well-explored, however, in contrast the impact of prevalent mutations in the mitochondrial genome, present in more than 75% of all cancers remain largely unexplored and are an emerging frontier in cancer research.
Using large-scale patient sequencing and clinical data, the Gammage group and others have demonstrated that this major and understudied class of cancer-associated mutations contained within the mitochondrial DNA are associated with substantial impact on tumour characteristics and clinical outcomes [Gorelick et al., 2021]. Intriguingly, these impacts appear to be specific to the tissue lineage from which the tumour was initiated and the type of mutations found in the mtDNA, with colorectal cancers demonstrating the clearest signal.
Employing a complement of cellular and animal models of tumour biology alongside state-of-the-art mitochondrial genome engineering tools and metabolic analyses, this project will tease apart the lineage-specific impacts of highly recurrent cancer-associated mtDNA mutations on tumour metabolism, potentially revealing metabolic dependencies and therapeutic opportunities that have not been identified previously.