Project MicroAge: A tissue engineered discovery platform for improving muscle responses to exercise in ageing and spaceflight

Summary: Astronauts lose muscle mass despite performing considerable exercise in space, since their cellular adaptation to exercise is somehow abnormally impaired by microgravity. On Earth, our muscles also respond less well to exercise as we get older, resulting in reduced muscle mass, loss of strength and frailty.

Our team have demonstrated that reactive oxygen species (ROS) generated during exercise stimulate the activation of specific transcription factors which increase the production of cytoprotective proteins. However, these responses are impaired in muscle from older humans, and analogously may also be attenuated in astronauts in microgravity. This comparison is the basis for our current research at MicroAge, and to do this we have constructed an experimental bioreactor that will soon fly on the International Space Station. The bioreactor uses an 'organ-on-a-chip' type technology to support bioengineered micro-muscles created from human cells, with microfluidic plumbing to refresh nutrients and collect secreted biomolecules, and an electrical stimulation circuit to enable the micro-muscles to undergo contractile exercise.

One of our goals is to discover drugs which correct the faulty signalling, since these will help us maintain muscle mass as we age and will enable longer-duration (e.g. interplanetary) spaceflight missions. As part of our team, you will use our existing muscle bioreactor to investigate interventional drugs that can restore the ability of human muscle to respond to exercise during ageing (or in spaceflight). Your initial project goals will be:

1. To determine key biomarkers (cytokines, myotube diameter, mitochondrial respiration rate, force generation, etc.) and develop practical methods to measure them.

2. To test the effectiveness of novel drugs, nutritionally-derived supplements, and gene/cell therapies to recover and rescue the phenotype of aged muscles.

You will get training in a wide range of interdisciplinary skills (how biology interfaces with mechanical and electrical engineering), learn how we translate basic scientific discoveries into therapeutics, and develop highly valuable quantitative skills. The project links biology across multiple scales: from biochemical signals, through organelles and cells, to visible changes is tissue function. The collaboration with industry and our ongoing acquisition of multidimensional data from ISS microgravity experiments gives you a unique opportunity for developing new technology and underpinning world-leading scientific advances.

The DTP will enable you to work closely with our project partners at the UK Space Agency and Kayser Space Ltd., expanding our existing technology from a specific spaceflight application to a broader range of investigative uses in discovery medicine. Kayser have extensive experience of designing and manufacturing miniaturised bioreactor systems and will help you design, manufacture and test new hardware using commercially appropriate techniques and ISO/QA standards. You will also be encouraged to develop your skills in science commination via the UKSA and our exciting outreach programme involving patient groups, schools and the local community, and take charge of updating our interactive project app to support public awareness of our research.