A new platform to understand and control protein liquid-liquid phase separation

蛋白质可以经历液-液相分离(LLP)并形成液滴。这种自组装机制在生物学和疾病(如阿尔茨海默氏症和帕金森氏病)中发挥着核心作用。然而，由于缺乏在生物相关的复杂系统(如细胞)中监测它的分析工具，它在很大程度上仍然没有特征。环境响应探针提供了无与伦比的机会来探测细胞中的生物分子自组装事件，并提供了它们的位置、时间和下游结果的读出。在这个项目中，我们将首次提供一个定量监测活细胞中LLP的平台。我们将研究a-突触核蛋白，这是神经系统的一种关键蛋白质，其LLP被假设为对该蛋白的正常功能和诱导与帕金森病有关的淀粉样蛋白聚集具有重要作用。这个多学科项目将涉及生物物理蛋白质表征、光学探针开发和活细胞显微镜的组合。

Proteins can undergo liquid-liquid phase separation (LLPS) and form liquid droplets. This self-assembly mechanism plays a central role in biology and disease (e.g. Alzheimer's and Parkinson's disease). Nevertheless, it is still largely uncharacterised due to the lack of analytical tools to monitor it in biologically relevant complex systems, such as cells. Environmentally responsive probes offer unparalleled opportunities to probe biomolecular self-assembly events in cells and provide a read-out for their location, timing, and downstream consequences.In this project, we will deliver a platform to quantitatively monitor LLPS in live cells, for the first time. We will investigate a-synuclein, a crucial protein of the nervous system, whose LLPS has been hypothesised to be important for the protein's normal function and for inducing amyloid aggregation linked to Parkinson's disease. This multidisciplinary project will involve a combination of biophysical protein characterisation, optical probe development and live cell microscopy.