Probing formation and regulation of membraneless organelles using chemical biology

无膜细胞器是由小分子、脂质、蛋白质和核酸等生物分子组成的受控凝聚而成的细胞器，最近被证明在调节从信号转导和炎症到转录和蛋白质降解等广泛的细胞过程中发挥着关键作用。在这个项目中，我们将开发和应用化学探针和化学蛋白质组学方法来研究参与无膜细胞器的成分，特别是了解不同类别的蛋白质翻译后修饰(PTM)如何调节它们的形成和功能。例如，我们将结合通过邻近标记技术(APEX、TurboID、MicroMap)的化学标记和蛋白质脂肪作用的代谢化学标记来探索这种PTM的变化如何调节液-液相分离(LLP)。从长远来看，该项目将验证新的工具和方法，以支持这一重要的新兴领域，并建议为治疗目的操纵凝析油形成和调节的方法。

Membraneless organelles are formed by the regulated condensation of biomolecular components including small molecules, lipids, proteins, and nucleic acids, and have recently been shown to play a critical role in regulating a wide range of cellular processes, from signal transduction and inflammation to transcription and protein degradation. In this project, we will develop and apply chemical probes and chemical proteomic approaches to study the components engaged in membraneless organelles, in particular to understand how different classes of protein post-translational modifications (PTMs) regulate their formation and function. For example, we will combine chemical labelling through proximity labelling technologies (APEX, TurboID, microMap) with metabolic chemical tagging of protein lipidation to probe how changes in this PTM regulate liquid-liquid phase separation (LLPS). In the longer term, this project will validate new tools and approaches to enable this important emerging field, and suggest means to manipulate condensate formation and regulation for therapeutic purposes.