Genetic modifiers of dilated cardiomyopathy in adult Drosophila

描述(由申请人提供)： 这份提案描述了一项为期五年的培训计划，以发展心脏病学的学术生涯。 首席调查员在杜克大学完成了系统的医学住院医师培训 他目前正在同一家机构完成心脏病学奖学金培训。现在，他会的 通过独特的跨部门开发，扩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·罗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，该项目将包括生物医学工程助理教授约瑟夫·A·伊扎特博士和分子遗传学和微生物学助理教授休伯特·阿姆雷恩博士的专业知识。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。Rockman博士和Izatt博士的实验室最近的工作表明，光学相干断层扫描可以准确和快速地检测醒着的成年果蝇的正常和异常的心功能。这一建议假设，利用果蝇遗传学的研究可以导致识别导致人类扩张型心肌病的基因。1)探讨十指肠麻痹(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学机制。2)通过对成年果蝇进行全基因组筛选，找出导致心肌病的新基因。3)探讨影响成年果蝇扩张型心肌病存活和心功能的遗传机制。 (摘要结束)

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)