Title: Exploration Studentship: Molecular basis of muscle alteration in response to spaceflight
Funder: UK Space Agency

Abstract: The UK has recently endorsed human exploration of space with its first Astronaut completing an expedition on-board theInternational Space Station. Like other countries, the UK has agreed to a worldwide plan for human exploration of spacethat currently has manned missions to Mars as the long term goal. This goal poses technical challenges with respect toengineering appropriate spacecraft and associated subsystems as well as with preserving human health on long durationspace missions. Nine potentially mission limiting health risks have been identified for Mars missions. These include declineof muscle strength and aerobic capacity, an area that we have actively been researching both on-board the InternationalSpace Station and here on Earth. Over a number of years and spaceflight missions we have identified a consistent set ofmolecules that change in response to spaceflight and do so not only in Astronaut muscle but also in other animals such asmice and worms. By conducting experiments in worms on Earth we have been able to change the response of themolecules that change in response to spaceflight. Thus, we will now attempt to use these gene and drug therapies onboard the International Space Station to see if we can alter the response of worm muscle to spaceflight. If we aresuccessful these drug therapies can be trialed on mice and Astronauts and these gene therapies can be further exploredfor future drug therapies for Astronauts. Importantly, this project will allow the participation of a post-graduate student inthese experiments which provides a unique training opportunity for the next generation of human exploration researchers inthe UK. Accordingly, the student will also conduct some ground based studies that support the use of worms on deepspace exploration missions and others that explore how other molecular changes seen in spaceflown muscle can becountered to improve strength and/or aerobic capacity. Ultimately, if the student is successful we will not only have amolecular understanding of why muscle changes in flight and how to counter it but also well developed new experiments tofly on future exploration missions.

Lay abstract: Professor Nate Szewczyk, from the University of Nottingham, is the Principle Investigator of the Molecular Muscle experiment, due to be flown to the International Space Station (ISS) on SpaceX-16 flight at the end of 2018. This grant will support a post-graduate student to work with the experiment team, receiving training in the conduct of molecular mechanistic experiments to further understand why muscle declines in response to spaceflight and, potentially, how it can be countered as well as gaining experience in the conduct of an actual life sciences spaceflight mission to the International Space Station. The long-term goal of crewed missions to Mars poses technical challenges with respect to engineering appropriate spacecraft and associated subsystems as well as with preserving human health on long duration space missions. One of the potentially mission limiting health risks that has been identified for Mars missions is the decline of muscle strength and aerobic capacity. Over a number of years and spaceflight missions a consistent set of molecules has been identified that change in response to spaceflight and do so not only in astronaut muscle but also in other animals such as mice and worms. By conducting experiments in worms on Earth, researchers have found that they have been able to change the response of the molecules that change in response to spaceflight. Thus, they will now attempt to use these gene and drug therapies on board the International Space Station to see if they can alter the response of worm muscle to spaceflight. https://www.gov.uk/government/news/new-uk-projects-look-at-the-impact-of-spaceflight-on-the-human-body

Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL