CYCLIN DEPENDENT KINASE 5 IN CANINE MOTOR NEURON DISEASE

描述(改编自申请人的摘要)：Sherril L.Green，DVM， 博士，ACVIM文凭，曾担任临床实验室 在斯坦福大学做了两年的动物兽医。她 UCD理查德·武利特博士在神经科学方面的博士培训重点是 Tau蛋白磷酸化和蛋白激酶CDK5在啮齿动物模型中的表达 卒中。自完成博士学位以来，格林博士一直致力于 临床实验动物护理，特别是大型动物的重症监护 物种。格林博士计划利用拟议的研究来扩大她的 神经科学和蛋白质生物化学的背景，并发展技能 分子生物学虽然她对HCSMA的神经生物学感兴趣， 运动神经元病的动物模型。 格林博士的研究是由琳达·科克博士共同赞助的， 第一个建立HCSMA殖民地的比较神经病理学家和Dr。 詹姆斯·费雷尔，医学博士，生物化学家，以其在地图上的工作而闻名 激酶和细胞周期的关系。格林博士将在两家公司的实验室工作 科克博士拥有设备齐全的实验室，专门研究 比较神经病理学，和费雷尔博士，他有一个装备精良的 生化实验室。格林博士将评估CDK5在 HCSMA。她的初步数据显示，在这两个特定的 动物脊髓组织中CDK5的活性和蛋白水平 这种疾病是纯合子的。她提出的实验将涉及三个问题 基本问题：1)为什么在HCSMA中CDK5比活性增加？ 2)为什么在HCSMA中CDK5蛋白水平升高？3)CDK5 神经细丝上的磷酸化位点在HCSMA？

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?