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FUNCTIONAL GENOMICS AND PROTEOMICS TO REVEAL REPRODUCTIVE-TRACT SPECIFIC PROTEINS

功能基因组学和蛋白质组学揭示生殖道特异性蛋白质

基本信息

批准号：
9910421
负责人：
Thomas Garcia
金额：
$ 39.63万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9910421
关键词：
Ablation Advanced Development Autopsy CRISPR/Cas technology Cells Collaborations Contraceptive Agents Contraceptive methods Coupled Data Data Set Development Distal Duct (organ) structure Epididymis Fertility Fertilization Foundations Future Generations Genes Genomic approach Goals Hormonal Human Infrastructure Knockout Mice Lead Liquid substance Male Contraceptive Agents Mass Spectrum Analysis Mediating Methodology Methods Mus Pathway interactions Pharmacology Population Procedures Process Proteins Proteome Proteomics Publishing Rattus Research Rodent Role Sampling Speed Sperm Maturation Technology Testis The Cancer Genome Atlas Tissues Transcript Vertebrates Woman Work base cell motility contraceptive target druggable target experimental study functional genomics genetic analysis genetic approach human male human tissue innovation male men mouse genome new therapeutic target novel reproductive reproductive tract small molecule sperm cell sperm function synergism transcriptome transcriptome sequencing transcriptomics zygote

项目摘要

SUMMARY The overall goals of this proposal are to elucidate novel male reproductive tract-specific proteins through high throughput transcriptomics and proteomics approaches, and to focus on the genetic analyses of five novel genes with expression limited to the male reproductive tract. With the world population continuing its steep rise, the need for effective and reversible non-hormonal methods of fertility control for men, such as those available to women, is widely recognized. To date, hormonal male contraceptives have not been effective. Therefore, identification of novel druggable targets in sperm and the male reproductive-tract are required to advance development of male contraceptives. Despite significant advances in proteomics, a comprehensive human sperm proteome has not been established. Likewise, despite extensive transcriptomic data published from mouse and rat epididymal segments, few published datasets exist for human epididymis. As sperm progress along the epididymal duct, they are bathed in a specialized luminal fluid microenvironment that is crucial for their maturation and survival. Considering its essential role, the epididymis is a prime target for the development of contraceptives for men. The proposed research is anticipated to lay the groundwork for future development of male contraceptives against novel targets. Motile, mature sperm are essential for successful fertilization and our overall hypothesis is that undiscovered druggable targets exist in the human male reproductive tract that are critical for sperm maturation and function. Our specific aims are as follows: 1) Perform transcriptomic analysis of human epididymal segments to identify novel epididymis-specific druggable targets to interfere with sperm maturation; 2) Perform proteomic analysis of human sperm to identify novel sperm-specific druggable targets for contraception; and 3) Apply CRISPR/Cas9 in mice to validate key sperm or reproductive tract-specific proteins required for sperm function and/or fertilization. The end goal of the proposed to work is to lead to the identification of additional novel targets for which an interdisciplinary team will work toward. Our mechanistic studies will allow us to place these proteins into reproductive pathways and simultaneously determine the utility of each of these proteins as a contraceptive target.

总结