The York Physics of Pyrenoids Project (YP3): Nanostructured Biological LLPS:Next-Level-Complexity Physics of CO2-fixing Organelles

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Single celled algae are among the most productive of all organisms on Earth for capturing carbon, fixing approximately 30% of all global CO2, yet we still do not understand all of the coupled processes by which they do it. Central to the mechanism are remarkable microscopic and self-assembled 'droplets' within the algae called 'Pyrenoids.' These 'condensates' within the cells are remarkable in their ability to form and dissolve as required, and unusual in not possessing a lipid membrane covering. They concentrate the proteins that need to interact to harvest and fix CO2 from the environment. Pyrenoids belong to a class of such separated droplets under intense study currently, but are more complex than other types as they also contain internal lipid membrane structures as tubes or layers, and some additionally generate starch platelets on their surface They seem to build on principles of 'Liquid-Liquid Phase Separation' well-studied in non-living systems with experimental and theoretical methods from physics.The York Pyrenoid Physics Project (YP3) will bring physicists and biologists together in an intensively collaborative team, to identify the key components and mechanisms of self-assembly, function and dis-assembly of the pyrenoid. The team combines expertise in algal molecular/cell biology, novel biophysical experimentation and imaging, and theoretical/computational biological physics. YP3 impacts the physics of biological assembly, algal and food-chain biotechnology as well as carbon capture. It will also represent a step-change in complexity in biological liquid-liquid phase separation (LLPS).The team will survey the structure and genetics of a large family of algal pyrenoids, then focus on intensive studies of core examples using cutting-edge imaging techniques able to track individual protein molecules as they move around the cell in response to external signals. Simplified mixtures of pyrenoid components, such as the active protein Rubsico and its 'linker' proteins, will be extracted from algae and the co-operative behaviour studied through the same techniques in vitro. The experiments will inform and test a growing computational model of the self-assembling pyrenoid, which will in turn make predictions for further experiments. A final output of the project will be the knowledge-base, from the combined model and experimental data, necessary to guide an attempt to build an artificial test tube pyrenoid, a next step in biotechnology applications for carbon capture and synthetic pyrenoids in crops to improve yields.The early-career researchers in YP3 will have unparalleled training in interdisciplinary research methods, communication and project management, and participate in wider Physics of Life activities in the UK and US through the UK Physics of Life and the linked US Physics of Living Systems Networks. YP3 is also supported by a world-leading international advisory board, who will additionally host the researchers for training periods.