I am an MRC DiMeN PhD student applying super-resolution microscopy techniques to gain insight into the pathological remodelling that occurs to cardiomyocytes during heart failure.
My research career began with a BSc, Biological Sciences in Leeds, and was encouraged along with an SfE summer studentship at the University of Liverpool. I gained the qualification of MPhil, Adaptive Organismal Biology at the University of Manchester.
Personal website: https://tmdsheard.github.io/
Twitter: @tmdsheard https://twitter.com/TMDSheard
During my PhD I have applied the novel super-resolution technique expansion microscopy (ExM) to study cardiac remodelling in heart failure. The focus is typically on calcium nanodomains, which are clusters of the calcium channel known as the ryanodine receptor (RyR).
In particular, I used an improved version of ExM, which can achieve ~15 nm resolution, to look at the remodelling of calcium nanodomains (Sheard et. al. 2019, ACS Nano). With the resolution afforded by X10 ExM we could visualise individual proteins and were also able to map the locations of individually phosphorylated RyRs. We compared the proportion of phosphorylation in healthy cells to those in cells from hearts with right ventricular failure.
As part of my MPhil, I applied electron tomography (ET), a 3D form of conventional electron microscopy, to garner information about the layout of the calcium release units in avian hearts (Sheard et. al. 2019, J Exp Biol). I applied ET to tissue study the nearest neighbour distances between the calcium release units, and was also able to obtain 3D geometric information about the corbular SR, the internal calcium release unit in the chicken heart.
Sheard and Jayasinghe. Methods in Cell Biology (2020). "Enhanced expansion microscopy to measure nanoscale structural and biochemical remodeling in single cells".
Sheard et. al. ACS Nano (2019). "Three-Dimensional and Chemical Mapping of Intracellular Signalling Nanodomains in Health and Disease with Enhanced Expansion Microscopy".
Sheard et. al. Journal of Experimental Biology (2019). "3D ultrastructural organisation of calcium release units in the avian sarcoplasmic reticulum."https://jeb.biologists.org/content/222/7/jeb197640
Sheard et. al. bioRxiv (2020). "Peptide ligands of the cardiac ryanodine receptor as super-resolution imaging probes." https://www.biorxiv.org/content/10.1101/2020.06.26.131854v1
- PhD candidate, MRC DiMeN DTP, at the University of Leeds (present)
- MPhil in Adaptive Organismal Biology, at the University of Manchester (2016)
- BSc in Biological Sciences, with industrial placement, at the University of Leeds (2015)
Research groups and institutes