细胞通过不同的机制来维持胞内不同细胞器上的脂质组成。细胞器互作介导脂质转运在其中发挥重要作用。磷脂酰丝氨酸(PS)是一种重要的磷脂分子，在内质网上合成，并通过细胞器互作转运到质膜和线粒体上发挥功能。细胞内其它细胞器（包括高尔基体和内涵体）也有一定浓度的PS，但其运输途径与功能还基本没有被阐明。在已知PS合成和转运途径基础上还有许多重要科学问题亟待解决。包括1）PS转运的功能：不同细胞器上的PS所发挥的功能及具体作用机制；2）PS转运的新途径：PS转运到不同细胞器的新途径与调节分子；3）细胞器互作介导PS转运途径间的协调：介导PS转运的各细胞器互作途径之间如何协调，PS转运途径是否影响不同细胞器互作。针对上述科学问题，我们拟通过研究PS合成及其代谢和转运途径对细胞稳态的影响，并利用遗传筛选的手段，结合细胞成像和生化分析，鉴定新分子的功能与机制，进而回答细胞器互作如何调控PS运输与细胞稳态。

Cell maintains the lipid compositions of different organelles through distinct mechanisms. Organelle-contact mediated lipid transport plays important roles in maintaining lipid homeostasis and organelle-specific function. In mammals, PS comprises 5% ~ 10% of cellular membranes. It is synthesized in the ER and transported to other cellular locations, including mitochondria and plasma membrane. The specific functions and underlying mechanisms of PS in different organelles are not fully understood. Besides transporting to mitochondria and plasma membrane, how PS transport to other cellular locations and what the regulatory mechanisms are not known. Lastly, it is not known how cells coordinate or prioritize different organelle-contact mediated PS transport routes. In this proposal, based on our preliminary study on Drosophila PS synthetase (PSS), we will use genetic screen to identify new molecules and cellular pathways mediating PS transport. By studying the role of these molecules, the transportation routes involved and their effects on organelle-contacts, we will elucidate the global picture of organelle-contact mediated PS transport.