BEGIN:VCALENDAR VERSION:2.0 PRODID:-// BEGIN:VTIMEZONE TZID:Europe/London BEGIN:DAYLIGHT TZOFFSETFROM:+0000 TZOFFSETTO:+0100 TZNAME:BST DTSTART:19700329T010000 RRULE:FREQ=YEARLY;BYMONTH=3;BYDAY=-1SU END:DAYLIGHT BEGIN:STANDARD TZOFFSETFROM:+0100 TZOFFSETTO:+0000 TZNAME:GMT DTSTART:19701025T020000 RRULE:FREQ=YEARLY;BYMONTH=10;BYDAY=-1SU END:STANDARD END:VTIMEZONE BEGIN:VEVENT CATEGORIES:Babraham Seminar SUMMARY:Optical control of T-cell signalling dynamics - Dr John James\; Department of Medicine\, University of Cambridge DTSTART;TZID=Europe/London:20180322T130000 DTEND;TZID=Europe/London:20180322T140000 UID:TALK101059AT URL: DESCRIPTION:We have a near-complete characterisation of the co mponents for many biological signalling networks\, but their dynamic interconnections remain poorly understood. Current methods to investigate intrace llular signalling generally disrupt one point in t he network and compare cell function afterwards. H owever\, the intervention can never be made withou t perturbing the rest of the system and rarely pro vides the dynamic information required for a mecha nistic understanding of network function. We inves tigate cell signalling by providing quantitative a nd dynamic inputs to the intact network\, measure the corresponding functional outputs and then infe r characteristics of the underlying system. To ach ieve the required spatio-temporal control over sig nalling\, we have developed light-controlled biolo gical components that enable us to modulate both t he intensity and frequency of signalling within th e network. We currently focus on the intracellular signalling of T-cells\, an essential immune cell- type that detect infected cells and orchestrate th eir removal. \nI will discuss two projects from my lab in the talk. The first part is on LCK\, a tyr osine kinase that is essential for initiating T-ce ll antigen receptor (TCR) signalling. We have used genetic code expansion to engineer a photocaged v ersion of LCK that can be switched ‘on’ through br ief light stimulation. Using this approach\, we ha ve found that in live cells\, autophosphorylation of the LCK active-site loop is indispensable for i ts catalytic activity. We have leveraged the power of this approach to show that CD4 and CD8\, the T -cell coreceptors\, can enhance LCK activity\, the reby helping to explain their effect in physiologi cal TCR signalling. \nFor the second project\, we have engineered an optically-controlled chimeric a ntigen receptor (OptoCAR) that provides a means to rapidly and reversibly manipulate the flux throug h the TCR signalling pathway. We have used this ex citing new tool to directly investigate whether th e downstream signalling network has the capacity t o integrate or ‘remember’ previous antigen-present ing cell encounters\, and the timescales over whic h this could occur. \nUsing our new tools\, our ke y goal is to provide a quantitative understanding of how different T-cell inputs are decoded by the dynamics of the signalling pathways to specify the appropriate response. Through this\, we hope to d iscover parts of the network that could be fine-tu ned therapeutically to alleviate diseases when T-c ell function becomes deleterious. LOCATION:Babraham - The Cambridge Building\; Kings Hedges R oom CONTACT:Matt Humphries END:VEVENT END:VCALENDAR