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，是 ACVIM 的文凭，并曾担任临床实验室 过去两年在斯坦福大学担任动物兽医。 她的 都柏林大学 Richard Vulliet 博士的神经科学博士培训重点关注 啮齿动物模型中 tau 蛋白磷酸化和蛋白激酶 CDK5 中风。 自完成博士学位以来，Green 博士一直从事 临床实验动物护理，特别是大型动物的重症监护 种。 格林博士计划利用拟议的研究来扩展她的研究 神经科学和蛋白质生物化学背景，并培养以下方面的技能 分子生物学，同时追求她对 HCSMA 神经生物学的兴趣， 运动神经元疾病的动物模型。 Green 博士的研究由 Linda Cork 博士（DVM、PhD）共同发起。 首先建立 HCSMA 群体的比较神经病理学家，以及 Dr. James Ferrell，医学博士、哲学博士，生物化学家，因其 MAP 工作而闻名 激酶和细胞周期。 格林博士将在双方实验室工作 Cork博士拥有一个设备齐全的实验室，专门研究 比较神经病理学和费雷尔博士，他拥有设备齐全的 生物化学实验室。 Green 博士将评估 CDK5 在 HCSMA。 她的初步数据表明，具体的变化 动物脊髓样本中 CDK5 的活性和蛋白质水平 该疾病的纯合子。 她提出的实验将解决三个问题 基本问题：1) 为什么 HCSMA 中 CDK5 比活性增加？ 2) 为什么 HCSMA 中 CDK5 蛋白水平增加？以及 3) CDK5 是否 HCSMA 中神经丝上的磷酸化位点？

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?