Functional significance of hox genes in the epididymis

丹妮拉·邦加德纳博士致力于学术事业。，专注于生殖医学的基础研究，目标是成为独立的研究者。她目前的训练拓宽了她在生殖道细胞和分子生理学方面的知识。KO8将为她提供一个独特的机会，让她学习分子和细胞生物学中更先进的方法，并在实验规划和关键数据分析方面变得更加熟练和有经验。泌尿科致力于候选人的研究发展，并致力于确保受保护的研究时间。赞助商的生产性实验室、弗吉尼亚大学的分子和细胞核心设施，以及与S·H·斯克拉布尔博士和S.Zeitlin博士的合作。神经科学，UVA)为学习新的研究技术和解决科学问题的方法提供了良好的环境。重要的是，由具有相关但不同专业领域的资深调查员组成的候选人咨询委员会强烈支持这一项目。此外，B.Hinton博士(系)的专业知识。细胞生物学，UVA)和M.Wilkinson博士(系德克萨斯州休斯顿的M.D.安德森癌症中心)将为候选人成为一名独立研究人员的目标提供额外的支持。这项建议的长期目标是发现附睾节段功能发育和维持的潜在机制。精子在附睾中的成熟需要上皮基因产物以区域特有的模式表达。我们的假设是，HOX基因是这一过程的主要调节基因。已知这些基因在胚胎的节段性模式中起关键作用，但这些基因的成人功能尚不清楚。具体地说，建议开发内源性Hoxa-11基因的条件突变。推测Hoxa-11的下调途径包括作为DNA结合辅助因子的Meis 1和作为潜在靶点的L1-CAM。将分析这一途径中每个参与者的基因和蛋白质表达模式。由此产生的数据将被用作基线，以检验Hoxa-11的时间调节影响发育关键期和成人附睾功能的假设。最后，将研究特定的5‘HOX基因可以反式激活特定的下游靶标和DNA结合因子的假设。将使用广泛的现代研究技术，包括最先进的活体实验。这一建议的结果将为理解在某些形式的男性不育和某些儿科泌尿科发育不良中重要的基本生物学过程提供基本信息。

Dr. Daniela Bomgardner is committed to an academic career. , focusing on basic research in reproductive medicine with the goal of being an independent investigator. Her current training has broadened her knowledge in cellular and molecular physiology of the reproductive tract. The KO8 will provide a unique opportunity for her to learn more advanced methods in molecular and cellular biology and to become more proficient and experienced in experimental planning and critical data analysis. The Department of Urology is dedicated to the candidate's research development and is committed to ensure protected time for research. The combination of the sponsors productive laboratory, the molecular and cellular core facilities at UVA, and the collaboration with Dr.'s H. Scrable and S. Zeitlin (Dept. Neuro-science, UVA) provides and excellent environment for learning new research techniques and approaches to scientific problems. Importantly, the candidates advisory committee, composed of established investigator with pertinent but diverse areas of expertise, and is strongly supportive of this project. Moreover, the expertise of Dr. B. Hinton (Dept. of Cell Biology, UVA) and Dr. M. Wilkinson (Dept. of Immunology, M.D. Anderson Cancer Center, Houston, TX) will provide additional support for the candidate's goal of becoming an independent investigator. The long-term objective of this proposal is to discover the mechanism underlying the development and maintenance of segmental function in the epididymis. Sperm maturation in the epididymis requires epithelial gene products expressed in a region-specific pattern. Our hypothesis is that hox genes are master regulators of this process. These genes are known to be crucial in segmental patterning of the embryo, but adult function of these genes is unknown. Specifically, it is proposed to develop a conditional mutation of the endogenous hoxa-11 gene. It is hypothesized that the down-regulation pathway of hoxa-11 includes Meis 1 as a DNA-binding cofactor and L1-CAM as a potential target. The gene and protein expression pattern of each participant in this pathway will be analyzed. The resulting data will be used as a baseline to test the hypothesis that temporal regulation of hoxa-11 influences critical periods in development and adult epididymal function. Finally, the hypothesis, that specific 5' hox genes can transactivated particular downstream targets together with DNA-binding factors will be investigated. A broad spectrum of modern research techniques will be used including state-of- the-art in vivo experiments. Findings from this proposal will provide fundamental information for the understanding of basic biological processes important in certain forms of male infertility and in certain urological dysplasias in pediatric urology.