Large bowl-shaped structure of MG23 channel and typical recording of MG23 cation current oscillations.
Postdoctoral Research Assistant in Cardiac Physiology
My research is focused on the functional investigation of ion-channels that are present on intracellular Ca2+-stores in cardiac and skeletal muscle. These channels include not only known Ca2+-release channels such as ryanodine receptors (RyRs) but also novel, uncharacterised cation-channels with unknown physiological roles. For example, using single-channel techniques, I have provided evidence for a novel intracellular cation-conducting channel named mitsugumin23 (MG23), which can form large homo-multimeric structures and it is thought to be involved in the regulation of apoptotic signals in cells. I am also interested in understanding how RyR channels are modulated by other nearby proteins (such as MG23) that may be important in heart failure or other diseases that can lead to sudden cardiac death including junctophilin, calsequestrin and FKBP12/12.6. In a new project, I have been studying the actions of a group of drugs called ‘statins’, and researching into their side effects on muscle cells. I have discovered that a commonly used drug, simvastatin, affects the RyR channels in the heart differently to the RyR channels in skeletal muscle. These effects may contribute both to the usefulness of the drugs and to their side effects.
Simvastatin activates single skeletal RyR1 channels but exerts more complex regulation of the cardiac RyR2 isoform.
Venturi E. et al, (2018), Br J Pharmacol, 175, 938 - 952
Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A.
El-Ajouz S. et al, (2017), J Physiol, 595, 4769 - 4784
Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).
Grieben M. et al, (2017), Nat Struct Mol Biol, 24, 114 - 122
Differential Effects of Temperature and Lipids on the Gating of RyR and SR K+ Channels
El-Ajouz S. et al, (2016), BIOPHYSICAL JOURNAL, 110, 266A - 266A
Dampened Activity of Single Ryanodine Receptor Channels in Mice Devoid of TRIC-A
Witschas K. et al, (2016), BIOPHYSICAL JOURNAL, 110, 266A - 266A