Loughborough University is a top-ten rated university in England for research intensity (REF2014) and an outstanding 66% of the work of Loughborough’s academic staff who were eligible to be submitted to the REF was judged as ‘world-leading’ or ‘internationally excellent’, compared to a national average figure of 43%. In choosing Loughborough for your research, you’ll work alongside academics who are leaders in their field. You will benefit from comprehensive support and guidance from our Doctoral College, including tailored careers advice, to help you succeed in your research and future career. During exercise, and in the presence of sufficient oxygen, glucose is metabolised by muscle cells to produce pyruvate, a metabolic intermediate which is fed into the Kreb’s cycle in the mitochondria to produce large amounts of energy. Where oxygen is limited, for example during prolonged high intensity exercise, pyruvate is converted in the cytosol to lactate through a fermentation process involving the enzyme lactate dehydrogenase (LDH). By contrast, cancer cells always metabolise glucose through the lactate-producing pathway, regardless of the volume of oxygen available. This phenomenon, observed by Otto Warburg over 90 years ago, is known as aerobic glycolysis or “the Warburg effect”, and still remains one of the biggest unsolved mysteries in cancer biology. All tumour types display altered cellular energetics, however they also display great variability in the magnitude of lactate production. Moreover, whilst the amount of energy produced is lower through the lactate-producing pathway, the rate of energy production is much faster, with a net cumulative effect of producing similar amounts of energy. Moreover, the acidic microenvironment produced by lactate synthesis correlates with tumour invasiveness. The proposed project will look to quantify lactate production and produce metabolic flux maps in different cancer cell types under aerobic and anaerobic conditions by mimicking prolonged physical activity using an in vitro model of skeletal muscle. The data will be used to assess whether there are synergistic or deleterious effects on the rate of growth and invasive potential of cancer cells cultured in the presence of exercised skeletal muscle models.