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

单细胞藻类是地球上捕碳效率最高的生物之一，固定了全球约30%的二氧化碳，但我们仍然不了解它们捕碳的所有耦合过程。这一机制的核心是一种名为“类Pyrenoids”的藻类中显著的微观和自组装的“液滴”。这些“凝聚物”在细胞内的形成和溶解能力是显著的，不具有脂质膜覆盖是不寻常的。它们浓缩了需要相互作用来从环境中收集和固定二氧化碳的蛋白质。类pyrenoid属于目前正在研究的一类分离液滴，但比其他类型的液滴更复杂，因为它们内部也含有管状或层状的脂质膜结构，有些还在其表面产生淀粉片。它们似乎建立在“液-液相分离”原理的基础上，这一原理在非生命系统中得到了很好的研究，从物理学的实验和理论方法。约克类Pyrenoid物理项目（YP3）将物理学家和生物学家聚集在一个紧密合作的团队中，以确定类Pyrenoid自组装、功能和拆卸的关键成分和机制。该团队结合了藻类分子/细胞生物学，新型生物物理实验和成像以及理论/计算生物物理学方面的专业知识。YP3影响生物组装、藻类和食物链生物技术以及碳捕获的物理特性。它也将代表生物液-液相分离（LLPS）复杂性的一个阶级性变化。该团队将调查一个大型类pyrenoids藻类家族的结构和遗传学，然后专注于使用尖端成像技术对核心例子进行深入研究，这些技术能够跟踪单个蛋白质分子在细胞周围响应外部信号移动时的情况。简化的类芘成分混合物，如活性蛋白Rubsico及其“连接”蛋白，将从藻类中提取出来，并通过同样的技术在体外研究其合作行为。这些实验将为不断发展的自组装类芘计算模型提供信息和测试，从而为进一步的实验做出预测。这个项目的最终产出将是一个知识库，它来自组合的模型和实验数据，这对指导建立一个人工类芘试管的尝试是必要的，这是生物技术应用于碳捕获和在作物中合成类芘以提高产量的下一步。YP3的早期职业研究人员将在跨学科研究方法，沟通和项目管理方面接受无与伦比的培训，并通过英国生命物理和相关的美国生命系统网络物理参与英国和美国更广泛的生命物理活动。YP3还得到了世界领先的国际咨询委员会的支持，该委员会将额外接待研究人员进行培训。

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.