Regulation of a Pacemaker Neural Output in Drosophila Circadian Rhythms

果蝇昼夜节律中起搏器神经输出的调节

• 批准号: 7477144
• 负责人: BRIDGET C LEAR
• 金额: $ 9万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7477144
• 关键词: Abdomen; Address; Alleles; Award; Behavior; Binding; Biochemical; Biological Models; Bipolar Disorder; Caenorhabditis elegans; Circadian Rhythms; Development; Disease; Drosophila genus; Drosophila melanogaster; Equipment; Excision; Exhibits; Faculty; GDF15 gene; Genes; Genetic; Goals; Health; Homologous Gene; Human; Ion Channel; Mammals; Mentors; Mission; Molecular Genetics; National Institute of General Medical Sciences; Neurons; Occupations; Output; PLAB Protein; Pacemakers; Phase; Phenotype; Phosphoric Monoester Hydrolases; Postdoctoral Fellow; Protein Phosphatase 2A Regulatory Subunit PR53; Proteins; Purpose; Regulation; Research; Research Personnel; Role; Seasonal Affective Disorder; Testing; Time; Training; Transcript; Transgenes; Transgenic Organisms; Universities; base; career; circadian pacemaker; mutant; neurogenetics; neuroregulation; novel; programs; relating to nervous system; research study

DESCRIPTION (provided by applicant): A central purpose of this award is to provide training to the grantee for successful transition from postdoctoral fellow to independent investigator. During the mentored phase of the proposal, Dr. Lear will obtain technical training and career guidance from the mentor, Dr. Ravi Allada, and co-mentor, Dr. Fred Turek. All facilities and equipment necessary to provide this training are available at Northwestern University. The mentored phase will also allow time for other career development activities, including the faculty job search. In the independent phase, Dr. Lear will use the training received and previous expertise in order to perform and direct the experiments outlined in the research plan. The long-term of goal of the candidate is to establish a successful independent research program studying the neural and genetic basis of circadian behavior, using the model system Drosophila melanogaster. The goal of the research plan outlined here is to elucidate regulatory mechanisms of circadian neural output, using genetic, molecular, and biochemical approaches. Previous research has demonstrated that putative ion channel narrow abdomen (na) functions in output of Drosophila circadian pacemaker neurons. However, little is known about regulation of na, and the circadian regulation of neural outputs remains poorly understood in both Drosophila and mammals. A novel Drosophila mutant, dunc-79, exhibits a strong decrease in NA expression levels and displays circadian phenotypes similar to those of na mutants, dunc-79 encodes a novel protein with homologs in C. elegans and mammals, and preliminary evidence suggests that this gene may be circadianly regulated. This proposal will examine the role of the dunc-79 in circadian rhythms and NA regulation. The specific aims of this proposal are as follows: (1) to examine the role of dunc-79, a putative NA regulator, in Drosophila circadian rhythms; (2) to examine the mechanism of dunc-79 regulation of NA; (3) to test the hypothesis that dunc-79 is circadianly regulated. This proposal is highly relevant to the mission of NIGMS to elucidate the neurogenetics of behavior. The proposed research plan also has significant implications for human health. Defective circadian rhythms are associated with disease states including bipolar disorder and seasonal affective disorder. Moreover, circadian rhythms genes originally identified and characterized in Drosophila have been shown to have similar function in mammals, including humans.

描述(由申请者提供)：该奖项的一个主要目的是为受赠者提供成功地从博士后研究员过渡到独立研究人员的培训。在提案的指导阶段，李尔博士将从导师拉维·阿拉达博士和共同导师弗雷德·图雷克博士那里获得技术培训和职业指导。西北大学提供了提供这种培训所需的所有设施和设备。辅导阶段还将为其他职业发展活动留出时间，包括教师求职。在独立阶段，李尔博士将利用所接受的培训和之前的专业知识来执行和指导研究计划中概述的实验。候选人的长期目标是建立一个成功的独立研究计划，研究昼夜行为的神经和遗传基础，使用模型系统黑腹果蝇。 这里概述的研究计划的目标是利用遗传学、分子和生物化学方法阐明昼夜节律神经输出的调节机制。以往的研究表明，果蝇昼夜节律起搏神经元的输出中可能存在离子通道窄腹(NA)。然而，对NA的调节知之甚少，在果蝇和哺乳动物中对神经输出的昼夜调节仍然知之甚少。一个新的果蝇突变体Dunc-79表现出NA表达水平的显著降低，并表现出与NA突变体相似的昼夜节律表型。Dunc-79编码一种在线虫和哺乳动物中具有同源物的新蛋白，初步证据表明该基因可能受到昼夜调控。这项提案将研究DUNC-79在昼夜节律和NA调节中的作用。这一建议的具体目的如下：(1)研究Dunc-79，一个可能的NA调节因子，在果蝇昼夜节律中的作用；(2)研究Dunc-79调节NA的机制；(3)检验Dunc-79是昼夜调节的假说。 这一建议与NIGMS阐明行为的神经遗传学的使命高度相关。拟议的研究计划对人类健康也有重大影响。昼夜节律缺陷与疾病状态有关，包括双相情感障碍和季节性情感障碍。此外，最初在果蝇中发现和表征的昼夜节律基因在哺乳动物中也具有类似的功能，包括人类。