Section Head: Dr Elisabeth Ehler
Deputy Head: Professor Pete Zammit
The Biology and Biomedicine of Striated Muscle
Striated muscle enables us to move and to live. Without skeletal muscle we would not be able to catch a bus or run away from a predator, while, without heart muscle, our blood would not be pumped around the body and the supply of oxygen and nutrients would cease.
The Muscle Biophysics Section at the Randall Centre for Cell &Molecular Biophysics studies all aspects of striated muscle function from the molecular, via the cellular, to the organismal level. We investigate the basics of muscle function in its smallest contractile unit, the sarcomere, and study how gene regulatory networks define the fate of a muscle cell. Since skeletal and heart muscle cells (cardiomyocytes) are terminally differentiated, the maintenance of their complex cytoarchitecture, as well as the regulation of protein turnover and disposal of damaged or mutant proteins, is especially relevant.
The striated muscle cells also respond to their environment and to changes in work load placed on them. This is explored in experiments that focus on mechanosignalling. The role of a particular type of stem cell, the satellite cell, in the maintenance of skeletal muscle is studied and we investigate the interaction between muscle cells and their surrounding tissue niche during the formation of limb muscle and the establishment of contacts between muscle and nerve cells.
We have a strong translational outreach and try to find out more about the underlying causes of muscular dystrophies, limb malformations, cardiomyopathies, critical illness myopathy and early-onset myopathies in children. Understanding the molecular basis of disease enables us to carry out high throughput screens for potential drugs that can halt disease progression.
In order to achieve our scientific goals, we employ not only conventional molecular biological, biochemical and cell biological techniques in the Muscle Biophysics section, but also try to harness cutting edge biophysical methodology for our experiments. This ranges from X-ray diffraction, nuclear magnetic resonance (NMR), fluorescence in situ spectroscopy, via ChIP-seq, RNA-seq, CRISP/Cas9 technology, mass spectroscopy, isothermal titration calorimetry, microscale thermophoresis, super resolution microscopy (STED and STORM) to electron microscopy tomography, optical projection tomography and whole animal imaging.
We use a variety of model systems, from cell cultures in 2D and 3D, to induced pluripotent stem cells, zebrafish and rodent models for myopathies. In collaboration with our clinical colleagues at King’s and abroad, we analyse samples from human patients to validate any findings made with animal models.
The Muscle Biophysics section has many active research links to clinical groups working on translational questions of muscle disease in children and adults, with joint grants and PhD students. Several members of the section are part of the KCL BHF Centre of Research Excellence together with the School of Cardiovascular Medicine and Sciences and one group is affiliated also with the Evelina London Children’s Hospital.
We organise the London Myology Forum together with colleagues from the MRC Centre for Neuromuscular Disease (Institute of Child Health (UCL), Institute of Neurology (UCL), University of Newcastle upon Tyne, and the Royal Veterinary College. This takes place twice a year to provide a regular platform for the presentation and discussion of basic and clinical research into muscle biology, disease, and therapy.
* also member of the School of Cardiovascular Medicine & Sciences