Collins Laboratory
The main focus of my laboratory is on the regulation of cardiac potassium channel expression by microRNA, particularly in the context of heart disease. Some potassium currents are downregulated during myocardial remodelling en route to heart failure, contributing to an increased risk of fatal arrhythmia. The ability to prevent this would require a thorough understanding of potassium channel regulation in this milieu.
Heart failure is associated with increased expression of certain microRNAs, and several of these are predicted to target important cardiac potassium channels. The main aims of this research are (1) Identify microRNA targets in cardiac potassium channel genes; (2) Demonstrate downregulation of cardiac potassium channels by specific microRNAs; and (3) Determine the effect of specific microRNA suppression on potassium channels in models of myocardial remodelling. The longer term objective is to develop microRNA-based therapies for controlling proarrhythmic myocardial remodelling in heart disease.
A second focus of my laboratory is on the role of ion homeostasis in cell proliferation and programmed cell death. Apoptosis, a form of programmed cell death, has been recognised as a normal process in tissue turnover and remodelling since the 1960’s. Dysfunction of apoptosis disturbs the balance between cell death and proliferation and is a feature of a number of degenerative and proliferative diseases, including some that fall within the research strategy of CVVS, e.g. diabetic retinopathy, macular dystrophy and tumour angiogenesis. Furthermore, the appropriate control of this balance would be essential in stem cells used for treating degenerative diseases.
During apoptosis the cell maintains a structural organisation, rather than simply lysing and releasing its contents into the surrounding tissue. This maintenance of structural integrity requires energy, so apoptosis is necessarily an energy-requiring process. Some of this energy requirement is for the active extrusion of osmolytes to counteract the osmotic pressure of membrane-impermeant intracellular organic molecules, which would otherwise cause the cell to swell and burst. Most animal cells use the plasma membrane Na+-K+ ATPase (Na+-K+ pump) as the primary pumping mechanism, but recent work shows that cells tend to lose Na+-K+ pump activity when undergoing apoptosis. Paradoxically, apoptotic cells do not swell and burst, even in the presence of Na+-K+ pump inhibitors. On the contrary, apoptosis is typically associated with volume decrease. Clearly the mechanism of cell volume control in apoptosis is not well understood. We aim to elucidate this mechanism by studying the ion channels and transporters involved.
Techniques used in my laboratory include patch-clamp, culture of primary cells and cell lines, RNA isolation, PCR, cloning, western blotting and apoptosis assays.
Collaborators include Dr. P. Slesinger (Salk Institute), Dr. D. Ma (University of California, Santa Barbara), Dr. J. Ishmael (Oregon State University), Prof. B. McDermott (QUB), Dr. D. Grieve (QUB), Dr. D. Simpson (QUB) and Dr. D. Bell (QUB).
Lab Members
Dr. Mary McGahon Postdoctoral Fellow
Ms. Dana Goldoni PhD student
Current and former research fellows, postgraduate, undergraduate, intercalated and summer students: Jennifer Lynch, Orla McDonnell, David Campbell, Orla McAvinchey, Tim Atkinson, Natalie Irwin, Lynn Morris, Janet Yarham, Davide Treggiari, Sara-Jane Conway, Ashley Hunter, Eimear McGreevy.