BioP Seminar - Prof. Anton Zilman (University of Toronto)

Start: May 1, 2019 11:00 AM

Location: UCL (MRC Building, LMCB, 2nd Floor Seminar Room)

Title: Specificity and accuracy of receptor signaling in the presence of cross-talk

Abstract: Cross-wired signaling pathways are common in cell signaling, whereby multiple signaling molecules share cell surface receptors or other pathway components. It remains  unclear how cells are able to reliably transmit information in cross-wired pathways. This issue features prominently in Type Interferon (IFN) signaling – a family of cytokines of the immune system, crucial for the response of  an organism to infection. In particular, several different IFN subtypes act through the same surface receptor but produce different outcomes in terms of cell function and fate. Using theoretical modeling and quantitative experiments, we systematically investigate factors responsible for the specificity of Type I IFN signaling. We show that the specificity arises from the interplay of the receptor binding affinity, the numbers of receptor sub-units and their in-membrane mobility, amplified by transcriptional negative feedback. We also formulate a general theoretical framework which shows how multiple ligands can be accurately sensed in the presence of cross-talk, and discuss the implications for other signaling pathways.