Genetic modifiers of dilated cardiomyopathy in adult Drosophila

成年果蝇扩张型心肌病的遗传修饰

• 批准号: 7670276
• 负责人: Matthew J Wolf
• 金额: $ 12.62万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670276
• 关键词: Academic Medical Centers; Address; Adult; Biochemical Genetics; Biological Models; Biology; Biomedical Engineering; Bone Morphogenetic Proteins; Breeding; Cardiac; Cardiology; Cardiomyopathies; Cardiovascular Diseases; Clinical; Collaborations; Development; Dilated Cardiomyopathy; Dimensions; Disease model; Drosophila genome; Drosophila genus; Embryo; Evaluation; Fellowship; Functional disorder; Gene Mutation; Gene-Modified; Generations; Genes; Genetic; Genetic Screening; Genetic Variation; Genomics; Genotype; Goals; Heart failure; Human; Human Genetics; Human Identifications; Individual; Institution; Laboratories; Lead; Maps; Measurement; Medical; Medicine; Mentors; Microbiology; Molecular Genetics; Mutation; Optical Coherence Tomography; Orthologous Gene; Phenotype; Phosphorus; Principal Investigator; Quantitative Trait Loci; Recombinant Inbred Strain; Research Personnel; Residencies; Scientist; Severities; Severity of illness; Signal Pathway; Signal Transduction; Single Nucleotide Polymorphism Map; Structure; Time; Training; Training Programs; Troponin I; Wolves; Work; abstracting; awake; base; career; cost; density; field study; fly; gastrulation; genome wide association study; heart function; human chordin; inhibitor/antagonist; innovation; novel; professor; programs; receptor; skills; trait

DESCRIPTION (provided by applicant): This proposal describes a five year training program to develop an academic career in Cardiology. The principal investigator has completed structured residency training in Medicine at Duke University Medical Center and is completing Cardiology fellowship training at the same institution. Now, he will expand upon his clinical and scientific skills through uniquely developed interdepartmental collaborations and mentoring. This program will develop a new field of study, namely the integration of Drosophila genetics and human cardiovascular disease to identify novel genes that cause dilated cardiomyopathy. Dr. Howard Rockman will mentor the principle investigator's scientific development. Dr. Rockman is a recognized leader in the field of receptor biology and the genetics of cardiomyopathy and heart failure. To enhance the training, the program will include the expertise of Dr. Joseph A. Izatt, Assistant Professor of Biomedical Engineering and Dr. Hubert Amrein, Assistant Professor in Molecular Genetics and Microbiology. In addition, a committee of highly-regarded medical scientists will provide scientific and career advice. Recent work in the laboratories of Drs. Rockman and Izatt has demonstrated that optical coherence tomography can accurately and rapidly detect normal and abnormal cardiac function in awake, adult Drosophila. This proposal hypothesizes that studies employing of Drosophila genetics can lead to the identification of genes causing human dilated cardiomyopathies. The specific aims are to: 1) Investigate the biochemical and genetic mechanisms through which mutations in the decapentaplegic (dpp) / bone morphogenetic protein (BMP) signaling pathway lead to dilated cardiomyopathy in adult Drosophila. 2) Identify novel genes that cause cardiomyopathy through a genome-wide screen of adult Drosophila. 3) Investigate the genetic mechanisms that modify survival and cardiac function in adult Drosophila with dilated cardiomyopathy. (End of Abstract)

描述（由申请人提供）： 该提案描述了一个为期五年的培训计划，以发展心脏病学的学术生涯。 主要研究者已在杜克大学完成了结构化的医学住院医师培训 医疗中心，并正在同一机构完成心脏病学进修培训。现在，他将 通过独特发展的跨部门拓展他的临床和科学技能 合作和指导。该计划将开发一个新的研究领域，即整合果蝇遗传学和人类心血管疾病，以确定导致扩张型心肌病的新基因。霍华德·洛克曼博士将指导首席研究员的科学发展。洛克曼博士是受体生物学以及心肌病和心力衰竭遗传学领域公认的领导者。为了加强培训，该计划将包括生物医学工程助理教授 Joseph A. Izatt 博士和分子遗传学和微生物学助理教授 Hubert Amrein 博士的专业知识。此外，一个由备受尊敬的医学科学家组成的委员会将提供科学和职业建议。博士实验室的最新工作。洛克曼和伊扎特已经证明，光学相干断层扫描可以准确、快速地检测清醒的成年果蝇的正常和异常心脏功能。该提议假设，利用果蝇遗传学的研究可以识别导致人类扩张型心肌病的基因。具体目标是：1）研究十五肢麻痹（dpp）/骨形态发生蛋白（BMP）信号通路突变导致成年果蝇扩张型心肌病的生化和遗传机制。 2) 通过成年果蝇的全基因组筛选，鉴定导致心肌病的新基因。 3) 研究改变患有扩张型心肌病的成年果蝇的生存和心脏功能的遗传机制。 （摘要完）