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

蛋白质可以进行液-液相分离（LLPS）并形成液滴。这种自组装机制在生物学和疾病（如阿尔茨海默病和帕金森病）中起着核心作用。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是未表征的。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、时间和下游后果的读数。在这个项目中，我们将首次提供一个定量监测活细胞中LLPS的平台。我们将研究a-突触核蛋白，一种神经系统的关键蛋白，其LLPS被假设对蛋白质的正常功能和诱导与帕金森病相关的淀粉样蛋白聚集很重要。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结合。

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.