Endoplasmic Reticulum; Molecular Biology; Nuclear Envelope; Organelles; Caenorhabditis elegans; Lamins; Lipid Metabolism; Diseases
Public Health Interests
Yale Combined Program in the Biological and Biomedical Sciences (BBS): Biochemistry, Quantitative Biology, Biophysics and Structural Biology (BQBS): Membrane Biology
Our lab is focused on understanding mechanisms that control membrane dynamics at the nuclear envelope to ensure genome protection during early embryogenesis and somatic cell division.
Extensive Research Description
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.
Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair
Penfield L, Wysolmerski B, Mauro M, Farhadifar R, Martinez M, Biggs R, Wu HY, Broberg C, Needleman D, and Bahmanyar S. (2018) Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair. Molecular Biology of the Cell. doi:10.1091/mbc.E17-06-0374 [Epub ahead of print]
Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown
Bahmanyar S, Biggs R, Schuh AL, Desai A, Muller-Reichert T, Audhya A, Dixon JE, and Oegema K. (2014) Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown. Genes Dev. 28(2):121-126
Nuclear envelope phosphatase 1-regulatory subunit 1 (formerly TMEM188) is the metazoan Spo7p ortholog and functions in the lipin activation pathway
Han S*, Bahmanyar S*, Zhang P, Grishin N, Oegema K, Crooke R, Graham M, Reue K, Dixon JE, and Goodman JM. (2011) Nuclear envelope phosphatase 1-regulatory subunit 1 (formerly TMEM188) is the metazoan Spo7p ortholog and functions in the lipin activation pathway. J Biol Chem. 287(5):3123-37.
Full List of PubMed Publications
- Penfield L, Wysolmerski B, Mauro M, Farhadifar R, Martinez MA, Biggs R, Wu HY, Broberg C, Needleman D, Bahmanyar S: Dynein-pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair. Mol Biol Cell. 2018 Jan 31; 2018 Jan 31. PMID: 29386297
- Weicksel SE, Mahadav A, Moyle M, Cipriani PG, Kudron M, Pincus Z, Bahmanyar S, Abriola L, Merkel J, Gutwein M, Fernandez AG, Piano F, Gunsalus KC, Reinke V: A novel small molecule that disrupts a key event during the oocyte-to-embryo transition in C. elegans. Development. 2016 Oct 1; 2016 Aug 10. PMID: 27510972
- Bahmanyar S: Spatial regulation of phospholipid synthesis within the nuclear envelope domain of the endoplasmic reticulum. Nucleus. 2015; 2015 Feb 11. PMID: 25671705