Shirin Bahmanyar, PhD

Our lab is interested in mechanisms that drive organelle structure, identity, and dynamics. In particular, we study the nuclear envelope - a specialized compartment that surrounds and protects the genome. The nuclear envelope is highly dynamic in both interphase and mitotic cells. Defects in nuclear envelope dynamics cause DNA damage and disrupt nuclear functions and as such are highly relevant to disease, yet little is known about mechanisms that control membrane dynamics at the NE.

Membrane dynamics at nearly all membrane bound organelles depend on the composition of bilayer lipids. Almost nothing is known about the membrane lipid composition of the nuclear envelope. This is in part because the nuclear envelope is not a stand-alone organelle but is continuous with the expansive endoplasmic reticulum (ER) making it difficult to biochemically distinguish between their lipid content. The ER serves as a platform for de novo lipid synthesis. Because lipids diffuse rapidly in the two dimensional network of the ER and nuclear envelope it has long been assumed that their lipid composition is the same. However, emerging evidence suggests that the nuclear envelope harbors distinct regulators of phospholipid metabolism that may lead to its unique lipid composition.

Our lab harnesses the powerful tools to identify genetic pathways and gene function in C. elegans and cutting-edge microscopy approaches amenable to live imaging of mammalian cells to define mechanisms that control nuclear envelope dynamics. We study nuclear envelope reformation in mitosis and interphase nuclear rupture and repair - two specialized processes that require local and global changes in membrane structure and protein recruitment and as such provide tractable systems to dissect the molecular mechanisms underpinning lipid-mediated regulation of nuclear envelope dynamics in genome protection.