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I am a DPhil student funded by the British Heart Foundation and based in the Sitsapesan lab. The cardiac ryanodine receptor (RyR2) is located in the sarcoplasmic reticulum (SR) and is the main intracellular Ca2+ release channel in the heart with a crucial role in regulating contraction. My research aims to identify how RyR2 is regulated by physiological stimuli such as phosphorylation, by the lipid SR membrane environment and by other SR ion channels in the SR (for example, TRIC-A).
I am also investigating why specific single point mutations to RyR2 can cause life threatening arrhythmias as in the disease catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is a rare inherited heart arrhythmia found in young people and children, which can lead to sudden cardiac death. To investigate how mutations in RyR2 affect electromechanical coupling within the heart, I am using single ion-channel reconstitution experiments to elucidate differences in the biophysical properties of the mutated channel, as well as using patient derived induced pluripotent stem cells (IPSCs) and optical mapping to examine the effect of the mutation at the whole cell level.