BACs to the future: new genetic models for cardiovascular discovery

Abstract

One of the great challenges of modern biology is to contextualize highly detailed molecular discoveries in order to prioritize the most medically relevant events. The response to heart damage, for example, likely involves tens of thousands of cells of multiple lineages, each undergoing complex signalling cascades that trigger other equally complex molecular interactions including cell migration, lineage induction, secretion, fibrosis, and revascularization. In determining the relevance of discrete molecular events within these broader contexts, we often infer their involvement from experiments in isolated cells under somewhat artificial conditions. How do we know that these exquisitely specific events occur under realistic clinical conditions? If so, to what extent? At what point in the process do they occur (acute damage, repair, etc.)? And perhaps most importantly, are they critical to the process? In short, how do we answer as early as possible the ‘so what’ question with respect to our favourite protein–protein interaction, transcriptional induction, or other molecular event, and thereby avoid spending years studying a potential epiphenomenon? One approach is to do …