BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Metastable dynamics: rare events in cell biology - Jay Newby (Univ ersity of North Carolina ) DTSTART:20160427T140000Z DTEND:20160427T150000Z UID:TALK65888@talks.cam.ac.uk CONTACT:INI IT DESCRIPTION:I will discuss an emerging framework where the extensive and p owerful toolbox of deterministic dynamical systems can be used to study an important class of noise induced stochastic phenomena\, called metastable dynamics. Consider two trajectories: one deterministic and one perturbed by weak noise\, each having the same initial conditions. A single fluctuat ion is very unlikely to perturb the stochastic trajectory very far from th e deterministic trajectory\, and on short time scales the two remain close . On long time scales\, both trajectories approach a stable steady state.& nbsp\; Given enough time\, it is possible for a rare sequence of fluctuati ons to perturb the stochastic trajectory far enough that it moves toward a different steady state. Hence\, a stable steady state for a deterministic system becomes a metastable state under the influence of weak noise. I wi ll discuss two applications in biology.  \; 1. The first application is epigenetic switching in gene circuits\, the biological problem that fi rst motivated my research. It has been known for decades that gene express ion is strongly influenced by random forces within the cell. Rare events d riven by noise can cause a dramatic shift in the way a gene is expressed\, which can radically alter the state of a cell. One example is an altered state that imparts antibiotic resistance to e-coli bacteria. I will show t hat diffusion approximations\, widely used to study gene expression system s\, are inaccurate and unreliable for metastable phenomena. As an alternat ive\, I will propose a far more accurate direct method that eliminates the need for a diffusion approximation.  \; 2. The second application i s spontaneous neural activity. Intrinsic noise from molecular fluctuations of voltage-gated ion channels cause spontaneous activity that propagates into and affects local network function. \; A spontaneous action poten tial is a physical example of a new type of first-exit-time problem: the r andom time to initiate an excitable event in an excitable system with a si ngle fixed point. Using a metastable phase plane analysis\, I will show ho w noise induced excitable events in the stochastic Morris-Leccar model are initiated through a predictable sequence of events. In other words\, a si ngle mechanism explains how spontaneous activity is generated. Moreover\, the generating mechanism contradicts the current understanding of this phe nomena. \; It is widely believed that spontaneous activity in most neu rons is driven primarily by fast sodium channels\, because these channels govern the fast initiation stage of an action potential. Potassium chann els respond much more slowly and are responsible for reseting the membrane voltage at the final stage of the action potential. Contrary to the stand ard paradigm\, metastable dynamics predicts that the primary driving force behind spontaneous initiation is the slow potassium channel noise. LOCATION:Seminar Room 2\, Newton Institute END:VEVENT END:VCALENDAR