Endothelin A Signaling in Craniofacial Development

描述(由申请人提供)： 颌骨和喉部的大部分骨和软骨结构来自头神经脊细胞。这些细胞来自后脑，迁移到咽弓，在那里它们经历了增殖和分化程序，最终形成了头面部结构。虽然许多信号级联调节这一发育程序，但这些级联的效应器还没有明确的定义。这项独立科学家奖的申请要求应聘者提供工资支持，以阐明控制头神经脊细胞及其衍生物发育的内皮素-A受体信号的下游效应者。候选人将使用各种技术来实现这一目标，包括使用定制的cDNA微阵列分析基因组变化，以及使用2D-Gel电泳法和质谱仪分析蛋白质组变化。 应聘者的职业目标是建立一个积极的研究实验室，致力于了解正常和异常颅面发育的分子和细胞基础。这个实验室将服务于额外的目标，即培训博士后和博士后学生进行颅面研究。ISA将通过促进专门知识和研究活动的具体扩展，促进候选人作为独立调查员的发展。近期计划包括前往外部实验室，发展生产和分析大规模定制基因微阵列的专业知识，以及在路易斯维尔大学的核心蛋白质组学实验室和生物分子质谱学核心实验室学习蛋白质图谱和鉴定方面的现代技术。为了充分利用阵列和蛋白质组数据，候选人还将参加一门生物信息学课程，该课程旨在使研究人员能够编写程序来管理基因组和蛋白质组研究数据。该研究所的发展计划包括：提供可观的启动资金；在申请K02支持的时间段之后提供有保障的工资支持；允许候选人基本上全职进行研究：最低限度的部门职责；按照候选人的计划提供前往实验室的资金；提供资金聘请博士后研究员，为候选人实验室不断增长的研究计划做出贡献：参加每月旨在促进候选人研究计划发展的部门间和部门内讨论小组。 研究环境为促进科学增长和发展的科学互动提供了极好的机会。许多资深研究人员在路易斯维尔大学指导积极的研究项目，提供许多潜在的互动。重要的是，候选人的主席是一位研究面部出生缺陷的分子和细胞基础的知名研究员。他的个人互动以及他不断努力招募在颅面发育和遗传学领域拥有活跃研究项目的个人，都突显了他致力于建立一个强大的研究团队，进一步帮助候选人建立自己的研究项目。

DESCRIPTION (provided by applicant): Most bone and cartilage structures of the jaw and throat are derived from cephalic neural crest cells. These cells, arising from the hindbrain, migrate to the pharyngeal arches, where they undergo a proliferation and differentiation program culminating in the formation of craniofacial structures. While numerous signaling cascades regulate this developmental program, the effectors of these cascades are poorly defined. This Independent Scientist Award application requests salary support for the candidate to elucidate the downstream effectors of endothelin-A receptor signaling that control development of cephalic neural crest cells and their derivatives. The candidate will use a variety of techniques to accomplish this aim, including analysis of genomic changes using custom cDNA microarrays and analysis of proteomic changes using 2D-gel electrophoresis and mass spectroscopy. Career goals of the candidate are centered on developing an active research laboratory dedicated to understanding the molecular and cellular basis of normal and abnormal craniofacial development. This lab will serve the additional goal of training pre- and post-doctoral students in craniofacial research. An ISA will enhance the candidate's development as an independent investigator by enabling specific expansion of expertise and research activities. Immediate plans include traveling to an external laboratory to develop expertise in the production and analysis of large-scale custom cDNA microarrays, as well as learning modern techniques in protein profiling and identification at the Core Proteomics Laboratory and the Biomolecular Mass Spectroscopy Core Laboratory, both at the University of Louisville. To take full advantage of the array and proteomic data, the candidate will also attend a bioinformatics course designed to enable researchers to write programs to manage genomic and proteomic research data. The Institution's development plans include: provision of significant start-up funds; guaranteed salary support beyond the period of time requested for K02 support; permission for the candidate to spend essentially full-time conducting research: minimal departmental duties; funds to travel to laboratories as outlined in the candidate's plans; provision of funds to hire a post-doctoral fellow to contribute to the growing research program in the candidate's laboratory: participation in monthly inter- and intra-departmental discussion groups designed to facilitate the development of the candidate's research program. The research environment offers excellent opportunities for scientific interactions that foster scientific growth and development. Many senior investigators direct active research programs at the University of Louisville, offering many potential interactions. Importantly, the candidate's chairman is a well-established investigator studying the molecular and cellular basis of facial birth defects. Both his personal interaction as well as his continuing efforts to recruit individuals with active research programs in the areas of craniofacial development and genetics underscores the commitment to build a strong research group, further helping the candidate build his own research program.