Niall Macquaide

Biography

I graduated from Glasgow in 2001 with an honours degree in Physiology and went on to study for a PhD. Working with Prof. Godfrey Smith, I investigating spontaneous Ca2+ release in cardiac myocytes through experimental and computer modelling techniques. After attaining my PhD in 2005, I carried out postdoctoral work examining the electrophysiological remodelling which occurs through the progression of heart failure in a rabbit model of myocardial infarction. Through this work I carried out work in the lab of Prof Donald Bers in UC Davis, California. In 2009 I attained a Marie Curie Fellowship to work in Leuven, Belgium in the Lab of Karin Sipido to study how RyR cluster organisation is altered during atrial fibrillation. In addition to the core study, I co-supervised two PhD students and attained new skills in Super Resolution Microscopy. I currently hold a BHF intermediate research fellowship and a Marie Curie reintegration fellowship.

Research Interest

I am interested in the functional alterations in cardiac cells after remodelled after myocardial infarction. I use advanced imaging methodologies and analysis methods, to study Ca2+ subcellular Ca2+ release in living cells as well as super resolution microscopy to measure alterations in the organisation of cellular proteins. Ryanodine Receptor clustering. Using super resolution microscopy methods, I will measure clustering of ryanodine receptors (RyRs) with single protein accuracy and assess changes coincident with pathological remodelling following myocardial infarction (MI). Ca2+ release from individual clusters will be imaged using a high speed, highly sensitive confocal imaging system. The goal here is to assess the changes which occur in failing hearts, how this can lead to an arrhythmogenic phenotype and to determine novel therapeutic strategies. Ca2+-calmodulin-dependant kinease (CaMKII). CaMKII is shown to induce a “hyperphosphorylation” of RyR, with known pro-arrhythmogenic effects in MI. Using in-vitro transfection of primary isolated myocytes I will introduce genetically encoded probes to assess the activation status of this kinase and how this changes in an arrhythmogenic phenotype. In collaboration with my collaborators: Prof Donald M Bers & Dr Julie Bossuyt, UC Davis, CA I will determine how local Ca2+ gradients and CaMKII localisation may affect cellular function and changes in these activities within the context of pathological hypertrophic remodelling. Cytoskeletal proteins. The role of a relevant cytoskeletal protein (Juncophilin-2), which is thought to tether the surface membrane to that of the cell’s Ca2+ store will then be targeted to assess it’s role in the creation of identified Ca2+ signalling microdomains. An siRNA gene silencing virus against junctophilin-2 has been created by one of my collaborators (Dr X Wehrens, Baylor, TX, USA) and this will be used to study how loss of this protein disrupts Ca2+ signalling microdomain, as both down regulation of junctophilin-2 and irregular Ca2+ release are also observed after remodelling in several cardiac pathologies. Atrial structural remodelling after MI. In collaboration with Dr. Anthony Workman, I am investigating structural alterations in t-tubule membrane in patients with and without MI to investigate how this could be changes by post-MI remodelling. The role of PDE’s in the heart. In collaboration with Prof George Baillie, I am investigating the role of PDEs in the regulation of key players of cardiac calcium release and uptake. Using biochemical and physiological techniques to explore the interaction of these PDEs with RyR and SERCA/ phospholamban (PLB), to develop more targeted therapies in the future.