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Abstract: The specific response of cells to environmental inputs depends on their ability to accurately decode external chemical signals and incorporate this information into cytosolic molecular components. Immune cells, for example, must interpret the chemical signals of infection and disease and activate an appropriate host response, such as inflammation or cell death. The internal pathways that drive this decision-making process must function as information-processing machines, allowing cells to sense chemical information and generate sophisticated, multi-layered outputs. This demands precise spatial and temporal control of signaling components within the complex and dynamic environment of the cell's interior. One plausible mechanism for achieving complex signal processing that can produce multi-layered outputs is the assembly of subcellular compartments. These compartments, known as signalosomes, concentrate reactants at precise points in time and space within the cell. My lab has developed assays and technology to investigate how a specialized signalosome known as the Myddosome compartmentalizes signaling proteins and drives cellular computation. In my talk, I will reveal how we have been using high-resolution microscopy to understand the mechanism and logic of Myddosome assembly. Finally, I will discuss how we have taken a bottom-up approach and reconstructed innate immune signalosomes with diverse biochemical attributes. Using a bottom-up approach, we have found that functional signalosomes can be constructed from natural and synthetically designed protein polymers. We have identified that high protein polymer stability is required for the localization and activation of downstream signaling reaction proteins.

Host: Kabir Haussain (kabir.husain@ucl.ac.uk)