BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Genetics and the heartbeat - Andrew Grace (University of Cambridge ) DTSTART:20250904T123000Z DTEND:20250904T133000Z UID:TALK235342@talks.cam.ac.uk CONTACT:Spencer Keene DESCRIPTION:One significant challenge for translational biology is underst anding how genomic variation affects temporo-spatial and quantitative expr ession of genes\, the activity and localisation of proteins and how these relate to physiological function. In this presentation I will argue that ‘human heart excitation’ provides an appealing model system for examin ation. \n\nCardiac excitation is highly evolved\, stable\, robust\, essent ially genetic and safely measurable clinically\, with patterns of activity highly quantifiable. Furthermore in the population electrocardiograms pro vide for readily applicable phenotyping as a comparator at scale and we al so have hugely abundant albeit yet to be understood GWAS data. \n\nDisturb ances of the heartbeat (arrhythmias) have major public health impacts incl uding sudden death\, heart failure and stroke and greater understanding of their underlying biology will be invaluable. \n\nThe presentation will fi rst consider how linkage analysis identified candidate disease genes encod ing ion channels and how these were characterized using model systems. I w ill go on to discuss deep intracardiac phenotyping of patients with geneti cally complex disease that has already facilitated both risk assessment an d guidance of therapy. I will then close by describing technology we have also developed to sample cells from human hearts with multiple clinical ap plications. Application of this approach will bridge critical gaps using s patial-omics to provide functional insights into tissue architectures unde rpinning excitation and the heartbeat itself. \n\nBio\n\nAndrew Grace is P rofessor of Experimental Cardiology at the University of Cambridge. He tra ined in cardiology in London and Cambridge and then delivered a consistent ly high-volume interventional practice focused on arrhythmias over >30 yea rs. He completed post-doctoral studies as a Fulbright Scholar in the Depar tment of Medicine\, University of California\, San Diego returning to Camb ridge as British Heart Foundation Senior Research Fellow. He is a recogniz ed innovator having a particular interest in ‘disruptive’ technologies that have included devices\, diagnostics and drugs. Some of his work has changed practice significantly and he made some of the ‘most important c ontributions’ to the development and implementation of subcutaneous defi brillators. His clinical research focus is currently on both activation ma pping and risk prediction of ventricular fibrillation. He has spent over 2 5 years addressing the impact of genetic variation on the heartbeat and mo st recently has established a network of colleagues based respectively in Cambridge\, Seattle\, Sydney and San Diego to provide a physically robust model of cardiac electrical measurement extending from charge movements th rough structurally resolved sodium channels to surface recordings. Working with the Theory of Condensed Matter Physics Group (Cavendish Laboratory\, Cambridge) and the Wellcome Trust Sanger Institute high-resolution charge density mapping of cardiac activation is being linked to multi-omics in s ingle cells acquired through novel in vivo freeze-sampling\; there is high anticipation of therapeutic target identification and rescue.\n LOCATION:Heart and Lung Research Institute (R.100 to 102) END:VEVENT END:VCALENDAR