CYCLIN DEPENDENT KINASE 5 IN CANINE MOTOR NEURON DISEASE

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DESCRIPTION (Adapted from the applicant's abstract): Sherril L. Green, DVM, PhD, is a Diplomate of the ACVIM and has served as a clinical laboratory animal veterinarian at Stanford University for the past two years. Her doctoral training in neuroscience with Dr. Richard Vulliet at UCD focused on tau protein phosphorylation and the protein kinase CDK5 in rodent models for stroke. Since completing her PhD degree, Dr. Green has been engaged in clinical laboratory animal care, especially intensive care for large animal species. Dr. Green plans to use the proposed studies to expand her background in neuroscience and protein biochemistry and to develop skills in molecular biology while pursuing her interests in the neurobiology of HCSMA, an animal model for motor neuron disease. Dr. Green's research is co-sponsored by Dr. Linda Cork, DVM, PhD, a comparative neuropathologist who first established the HCSMA colony, and Dr. James Ferrell, MD, PhD, a biochemist who is well known for his work on MAP kinase and the cell cycle. Dr. Green will work in the laboratories of both Dr. Cork, who has a fully equipped laboratory that specializes in comparative neuropathology, and Dr. Ferrell, who has a well-equipped biochemistry laboratory. Dr. Green will evaluate the involvement of CDK5 in HCSMA. Her preliminary data demonstrate alterations in both the specific activity and protein levels of CDK5 in spinal cord samples from animals homozygous for the disease. Her proposed experiments will address three fundamental questions: 1) Why is CDK5 specific activity increased in HCSMA? 2) Why are CDK5 protein levels increased in HCSMA?, and 3) Are CDK5 phosphorylation sites on neurofilaments occupied in HCSMA?