The cell nuclear envelope is the physical barrier between the cytoplasm and the nucleus. The envelope regulates gene expression by allowing the access of proteins to DNA through passageways called nuclear pores. The nuclear envelope is unique in that it has two lipid bilayers (not one as is the case with cell membranes). The bilayers are maintained at a regular (and large) distance of nearly 45 nm. How these two bilayers are maintained at that regular spacing, and how they fuse together to form nuclear pores are current open questions in biology; this award is focused on answering these questions. By discovering an explanation for protein-mediated control of bilayer separation, this research will ultimately help develop new strategies for treating diseases that have been linked to mutations in the nuclear envelope proteins. The research program will provide opportunities to recruit outstanding students from underrepresented groups at the University of Houston (UH) and the University of Florida (UF). The findings of the research will be disseminated through journal publications, conference presentations and graduate and undergraduate courses at UH and UF.
This award will promote a collaborative partnership between investigators involving experiments, modeling and simulations to elucidate the fundamental physics that underlies nuclear lipid bilayer structure. The experimental work will discover how SUN proteins, which are conserved across different eukaryotic cell types and link the nucleus to the cytoskeleton maintain lipid bilayer structure and integrity. Theoretical work will seek to interpret the experimental findings in the framework of continuum mechanics, by computing the energetics of bilayer separation and fusion. The numerical and experimental findings will be used together to explain the mechanism of bilayer separation.
