C. elegans for Humans
C. elegans for Humans
- Skeletal muscle is essential for maintaining the health of our whole body; when muscle is lost (e.g. in older age, bedrest, injury, spaceflight) we are much more likely to become ill and immobile.
- Our group aims to understand the signals that regulate muscle health in youth and older age.
- We use this information to inform new therapies that optimise exercise responsiveness and also promote healthy ageing.
- We take a translational approach that combines fundamental research in worms with human clinical trials.
Examples of our research
Click the links below to view publications related to each research area.
C. elegans research
We discovered that cell adhesion regulates specific muscle protein breakdown systems to maintain healthy muscle, and found that the complex cell adhesion system is required for keeping muscle healthy.
We have reported that mitochondrial function controls calcium levels in muscle cells which, in turn increases the breakdown of extracellular matrix and causes reduced muscle health.
We have established a C. elegans model for understanding the causes of, and countermeasures to, Duchenne Muscular Dystrophy.
We found that muscle from older people displays distinct molecular differences from younger adults after lengthening (eccentric) and shortening (concentric) contractions.
We demonstrated that the muscle growth response to eating a protein meal is short lived, despite the continued presence of molecular signals for muscle to grow.
We reported that large individual variability exists in muscle growth responses to exercise when breathing low oxygen air (hypoxia), whereby people that experience the biggest drop in blood oxygen levels during hypoxic exposure have the lowest growth responses.
We have shown that a breakdown product of the essential amino acid leucine stimulates muscle growth responses and influences muscle breakdown responses via independent molecular signals.
We demonstrated that spaceflight causes highly reproducible molecular changes in C. elegans, which are also seen in higher organisms including people. These molecular changes broadly relate to maintaining muscle structure and mitochondrial function (the part of our cells that produce most of our energy).
We developed an automated, remotely operated system that can culture C. elegans for 12 generations on the International Space Station, and that these animals display normal developmental timings and capacity for reproduction.
We found that fundamental cellular processes that regulate gene expression are unaltered across multiple C. elegans generations cultured in spaceflight.
We established that key growth factor signalling pathways are decreased during spaceflight, and that these can be restored by using centrifugation to mimic Earth's gravity.
In vivo work:
- Human clinical metabolic trials of exercise and drug intervention efficacy.
- High-throughput microfluidic lifespan and healthspan analysis in C. elegans.
In vitro work:
Tissue/cell culture, including primary human myogenic culture.
- Stable isotope tracer-based assessment of human metabolism.
- Detailed assessment of mitochondrial function.
- Transcriptomic, proteomic and metabolomic analysis of human muscle adaptation.
- Bioinformatic network analysis.
- Range of modern molecular biology techniques for quantifying molecular adaptation in humans and C. elegans.
|Dr Tim Etheridge||Senior Lecturer|
|Dr Colleen Deane||MRC Research Fellow|
|Dr Bridget Paling||Postdoctoral researcher|
|Craig Willis||BBSRC PhD student|
|Mike Cooke||STFC/ UK Space Agency PhD student|
|Ryan Frankum||PhD student|
|Emad Manni||PhD student|
|Luke Slade||PhD student|
Our spaceflight research has attracted international media attention including coverage from several TV, radio and newspaper outlets. Google search ‘Molecular Muscle Experiment’ for more information.