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Nicole Kendrick

Department: Biochemistry

Faculty Mentor: Adrian Olivares, Ph.D.

Dissertation DescriptionThe Role of Torsin in Remodeling Nuclear Envelope Proteins

Torsin belongs to the family of AAA+ (ATPases Associated with various cellular Activities) macromolecular remodeling enzymes proteins that utilize ATP to perform mechanical work, such as protein unfolding and degradation.  The physiological function of torsin is unclear, but it has been suggested through previous studies that it remodels nuclear envelope proteins, such as LINC (Linker of Nucleoskeleton and Cytoskeleton) components. The Olivares lab is interested in understanding how the LINC complex senses and uses mechanical forces to affect nuclear membrane position, alter chromosome dynamics, and control gene expression.  My research will be focused on how torsin remodels the LINC complex using biochemical methods, single molecule optical trapping, and through the development of small molecule agonists against torsin enzymatic and cellular function.  This will help to develop therapeutics for several diseases that have been linked to torsin mutations, such as early-onset torsin dystonia, a hereditary movement disorder that is characterized by repetitive and involuntary muscle contractions.