Using a novel 3D co-culture model to define metabolic flux maps of different cancer cell types in response to physical activity

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.
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Applications are invited from ambitious, self-motivated candidates to undertake a PhD in the field of musculoskeletal biology in the School of Sport, Exercise and Health Sciences at Loughborough University, who have at least an Upper Second Class Honours degree or equivalent in a biological or engineering related subject.

Loughborough University is one of the country’s leading university’s (Rank 7th in the Time Higher Education) and is world renowned for its research in sports related subjects (1st overall for sports related subjects in the QS world university rankings 2017).

Applicants will be joining a well-established research team working within the School of Sport, Exercise and Health Sciences, interested in the development of physiologically relevant models of skeletal muscle. Using Tissue Engineering applications, this research team has published extensively in the field of musculoskeletal biology.

Applications are invited from self-funded students who have an interest in research in the following areas:

• Muscle – nerve interactions
• Musculoskeletal disease
• Models of exercise in tissue engineered muscle
• Tissue engineered joints on a chip

http://www.lboro.ac.uk/departments/ssehs/staff/mark-lewis/
http://www.lboro.ac.uk/departments/ssehs/staff/mhairi-morris/
Entry requirements
-Applicants should have, or expect to achieve, at least a 2:1 honours degree (or equivalent) in sport and exercise science, human physiology, human biology, biochemistry or a related subject.
- All students must also meet the minimum English language requirements: http://www.lboro.ac.uk/international/applicants/english/
- A relevant master's degree and / or experience in one or more of the following will be an advantage: Human biology, exercise physiology, biochemistry, systems biology, metabolomics