Neurobehavioral Analysis of Norepinephrine Transporter Variants

去甲肾上腺素转运蛋白变体的神经行为分析

基本信息

批准号：
7172648
负责人：
MAUREEN K HAHN
金额：
$ 12.89万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7172648
关键词：
Active Biological Transport Amino Acids Anabolism Area Attention Autonomic nervous system disorders Award Behavior Behavioral Behavioral Assay Binding Biochemistry Biomedical Research Cardiovascular Physiology Cardiovascular system Catecholamines Cells Chromosome Pairing Chromosomes, Human, Pair 16 Clinical Cocaine Cognitive Complex Confocal Microscopy Core Facility Cultured Cells Development Development Plans Disease Disruption Doctor of Philosophy Educational process of instructing Employee Strikes Environment Exons Family Fellowship Generations Genes Genetic Genetic Variation Human Immunofluorescence Microscopy Impaired cognition In Vitro Introns Knock-in Mouse Knock-out Laboratories Learning Link Localized Measures Mediator of activation protein Memory Mentors Metabolism Methylphenidate Moods Mus Neurons Norepinephrine Performance Peripheral Phenotype Phorbol Esters Physiology Play Population Postdoctoral Fellow Preparation Principal Investigator Process Production Publications Regulation Research Research Personnel Role Scientist Serotonin Short-Term Memory Signal Transduction Single Nucleotide Polymorphism Sympathetic Nervous System Synapses System Technology Training Transgenic Mice Tricyclic Antidepressive Agents Universities Variant career design disorder risk dopamine transporter gamma-Aminobutyric Acid genetic variant inhibitor/antagonist instructor member mouse model neurobehavioral neuropsychiatry nisoxetine noradrenaline transporter noradrenergic novel presynaptic programs psychostimulant response reuptake success symposium trafficking trait transgene expression vector

项目摘要

DESCRIPTION (provided by applicant): The candidate's research record demonstrates a commitment to a career in biomedical research and, specifically, to understand the regulation of catecholamine (CA) systems physiology and their role in neuropsychiatric disease. Randy Blakely, serving as mentor of this application, has an outstanding research record and has mentored numerous postdoctoral fellows to successful careers as independent investigators. With the guidance of a mentoring committee, whose members are Ariel Deutch, Danny Winder and David Robertson, all experts in catecholamine system physiology and disease processes, we have incorporated into this application the components we deem critical to the candidate's scientific development. The application will provide novel training in the area of transgene expression of norepinephrine transporter genetic variants in primary noradrenergic neuronal culture and genetically altered mice, including use of immunofluorescence microscopy, transport assays and behavioral analyses to understand the impact of norepinephrine transporter genetic variants. Under the career development plan the candidate will participate in courses and seminars to receive didactic training and has also arranged to serve as instructor in several Vanderbilt courses. Vanderbilt University offers a superior environment to conduct the activities under this award, including core facilities for transgenic mouse production, mouse behavioral analysis and confocal microscopy. This application proposes approaches not presently applied in the Blakely laboratory to the study of the norepinephrine transporter, thus providing some novel and independent avenues of research. The candidate's successful publication record, recognition by various awards and fellowships and continued drive to learn and teach others through conferences, classroom teaching, or in the laboratory, demonstrate an exuberance, commitment and potential for success as an independent scientist. Relevance: The norepinephrine (NE) transporter (NET), is a mediator of NE inactivation by reuptake of NE into cells and may play a role in disorders of cardiovascular function, attention, memory and mood. Variation in NET genetic sequence, leading to altered NET protein, has been identified in humans. Selected genetic variants will be expressed in cells for activity and in mice for cardiovascular function and behaviors linked to memory and attention. Understanding the function of NET variants will contribute to our understanding of how genetic variation within NET contributes to human complex traits and disease

描述（由申请人提供）：候选人的研究记录表明了对生物医学研究职业的承诺，特别是了解儿茶酚胺（CA）系统生理学及其在神经精神病中的作用。兰迪·布拉克利（Randy Blakely）担任该应用程序的导师，拥有出色的研究记录，并指导了许多成功职业的博士后研究员，作为独立研究人员。在指导委员会的指导下，其成员是Ariel Deutch，Danny Winder和David Robertson，所有的Catecholamine System生理学和疾病过程专家，我们已将其纳入本应用程序中，我们认为对候选人的科学发展至关重要。该应用将在原发性去甲肾上腺素能神经元培养和遗传上改变的小鼠中去甲肾上腺素转运蛋白遗传变异的转基因表达方面提供新的培训，包括使用免疫荧光显微镜，传输测定法和行为分析，以了解诺甲肾上腺素转运蛋白遗传变异的影响。根据职业发展计划，候选人将参加课程和研讨会，以接受教学培训，并安排在几门范德比尔特课程中担任教练。范德比尔特大学（Vanderbilt University）提供了一个卓越的环境，可以在此奖项下进行活动，包括用于转基因小鼠生产，小鼠行为分析和共聚焦显微镜的核心设施。该应用提出了目前在Blakely实验室中未应用的方法来研究去甲肾上腺素转运蛋白，从而提供了一些新颖和独立的研究途径。候选人的成功出版记录，各种奖项和奖学金的认可，并继续开车通过会议，课堂教学或在实验室中学习和教别人，这表明了作为独立科学家的繁荣，承诺和成功的潜力。相关性：去甲肾上腺素（NE）转运蛋白（NET）是NE通过NE重新摄取细胞的NE失活的介体，并且可能在心血管功能，注意力，记忆和情绪的疾病中起作用。在人类中已经发现了净遗传序列的变化，导致净蛋白质改变。选定的遗传变异将在细胞中表达用于活性和小鼠的心血管功能以及与记忆和注意力相关的行为。了解净变体的功能将有助于我们理解净遗传变异如何对人类复杂性状和疾病有效