Defects in a cellular structure termed the nuclear envelope are associated with a myriad of diverse diseases, collectively called nuclear envelopathies. Most of these disorders clinically manifest during the first two decades of life and include muscular dystrophy, cardiomyopathy, lipodystrophy, dystonia, neuropathy, skeletal defects, and progeria. The nuclear envelope is situated at a critical juncture in the cell, both intimately associated with the genome and responsible for connecting it to the rest of the cell. While it is clear that mutations in genes encoding protein constituents of the nuclear envelope underlie these diseases, the exact mechanisms remain largely unknown. In part, these nuclear envelopathies involve a nuclear envelope structure called the LINC-complex that is responsible for linking the nucleoskeleton to the cytoskeleton.
Development and application of BioID: We developed BioID to overcome methodological challenges in our studies on the structure and function of the nuclear envelope in health and disease. First applied to a disease-associated nuclear lamin, we demonstrated that BioID is effective at identifying proximate and interacting proteins. Ongoing studies include the application of BioID to uncover the mechanisms of disease for the nuclear envelopathies, expansion of its application to a myriad of subcellular domains, and further optimization of the BioID system.
Characterization of novel LINC-complex constituents: We have discovered several novel members of a mammalian family of outer nuclear membrane (ONM) proteins that connect the nucleus to the cytoskeleton and/or retain specific proteins at the ONM. One of these proteins, which we have named Dalek6, appears to help connect chromosomes to molecular motors during meiotic prophase I. We are investigating the role of Dalek6 in regulating the movement of meiotic chromosomes during the process of homolog pairing and synapsis. Defects in these events may contribute to aneuploidy, a common cause of prematurely terminated pregnancies and birth defects such as Down syndrome.
Contact Information for Roux Lab:
Kyle J. Roux, PhD