Grant: Project Grant

Lipids are essential building blocks of cells, forming the membranes that surround and organize cellular compartments. To function properly, cells must transport lipids from where they are made - primarily the endoplasmic reticulum - to other parts of the cell. How this transport occurs inside living cells remains a central unanswered question in cell biology. A group of proteins known as bridge-like lipid transport proteins are thought to move lipids directly between cellular compartments at sites of contact between them. In humans, defects in these proteins are linked to severe neurological disorders, highlighting their importance for normal cellular physiology. However, understanding how these proteins work inside cells has been challenging because we lack tools to directly measure lipid transport in living systems. To overcome this limitation, we have developed a new method called METALIC (Mass tagging-Enabled TrAcking of Lipids In Cells), which allows us to follow the movement of lipids inside living cells. In this project, we will use METALIC together with complementary approaches to uncover how the founding member of this protein family, Vps13, transports lipids and how its activity is regulated by the metabolic state of the cell. By revealing the basic principles that govern lipid transport between cellular compartments, this research will provide fundamental insights into cell organization and lay the groundwork for future strategies to address diseases caused by defective lipid trafficking.