Functional Microscopy
Dr Julia Gorelik - Head of Group
The Functional Microscopy group focuses on the imaging of living cells and tissues in the cardiovascular system. In particular we use specialised microscopic technique -Scanning ion conductance Microscopy (SICM) to obtain information about signaling within cells as it happens in real time.
This scanning technique enables simultaneous recording of high-resolution topography of cell surfaces, intracellular fluorescence and measure mechanical properties of the cells and tissues such as cardiac valve and aorta.
The hybrid instrument also functions as a vastly improved patch-clamp system (the "smart patch"). This groundbreaking method has enabled several electrophysiological projects and avenues of research. We recently combined the SICM with ultra-fast optical recording of action potential and calcium transient for studying of cell-to-cell dynamic of coupling. Another combination allows us to record Foster Resonance Energy Transfer (FRET) together with topographical imaging at the same time.
Our aims
To discover the mechanisms of receptor/channels-mediated cellular response and intracellular signaling.
Our work can lead to the development of new therapeutic approaches to target various diseases of the cardiovascular system; in particular we are interested in the beta adrenergic receptors and cyclic nucleotide signaling.
Recently we found that the beta2AR receptors are normally anchored in the t-tubules, but in those cells damaged by heart failure they change location and move into the same space as beta1AR receptors.
The group is composed of several MRes and PhD Students, as well as postdoctoral researchers.
Selected Publications
Michele Miragoli - Research Associate
Sheikh Abdul Kadir SH; Miragoli M; Abu-Hayyeh S; Moshkov AV; Xie Q; Keitel V; Nikolaev VO; Williamson C; et al. (2010). Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One. 5:e9689.
Nikolaev VO; Moshkov A; Lyon AR; Miragoli M; Novak P; Paur H; Lohse MJ; Korchev YE; et al. (26 Mar 2010). Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science. 327:1653-1657.
Lyon AR; MacLeod KT; Zhang Y; Garcia E; Kanda GK; Lab MJ; Korchev YE; Harding SE; et al. (21 Apr 2009). Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart. Proc Natl Acad Sci U S A. 106:6854-6859.
Abdul Kadir SH; Ali NN; Mioulane M; Brito-Martins M; Abu-Hayyeh S; Foldes G; Moshkov AV; Williamson C; et al. (Sep 2009). Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease. J Cell Mol Med. 13:3730-3741.
Novak P; Li C; Shevchuk AI; Stepanyan R; Caldwell M; Hughes S; Smart TG; Gorelik J; et al. (Apr 2009). Nanoscale live-cell imaging using hopping probe ion conductance microscopy. NAT METHODS. 6:279-281.
Dr Julia Gorelik and members of her research group, July 2010
