Systems analysis of a critical regulatory hub in sex determination. This project seeks to better understand regulatory mechanisms of embryonic development. A key challenge in biology is to understand how genes act in regulatory networks to coordinate the formation of complex organs during embryo development. Although several genes influence embryo sex determination and gonad development, Sox9 has emerged as a master regulator in this system. This project plans to use new systems biology technolo ....Systems analysis of a critical regulatory hub in sex determination. This project seeks to better understand regulatory mechanisms of embryonic development. A key challenge in biology is to understand how genes act in regulatory networks to coordinate the formation of complex organs during embryo development. Although several genes influence embryo sex determination and gonad development, Sox9 has emerged as a master regulator in this system. This project plans to use new systems biology technologies and transgenic mice to identify the suite of Sox9 target genes and partner proteins. Anticipated outcomes include insights into sex determination, stem cell differentiation, and development of many other organ systems that depend on Sox9 function, providing proof-of-concept for high-throughput analysis of molecular control networks in the embryo.Read moreRead less
Switching on sex: How key mammalian sex-determining genes are activated. Development as a male or female is one of the most important biological decisions made during embryonic life. Although several of the key sex-determining genes are now known, it is unclear how they come to be active at the right time and in the right cells of the gonad to direct sex determination. This project aims to use bioinformatics, biochemistry, cellular assays and powerful genome editing technologies in mice to pinpo ....Switching on sex: How key mammalian sex-determining genes are activated. Development as a male or female is one of the most important biological decisions made during embryonic life. Although several of the key sex-determining genes are now known, it is unclear how they come to be active at the right time and in the right cells of the gonad to direct sex determination. This project aims to use bioinformatics, biochemistry, cellular assays and powerful genome editing technologies in mice to pinpoint essential regulatory elements and understand how they function. In addition to addressing key issues in mammalian molecular genetics and developmental biology, data generated in this project may provide a basis for innovative biotechnologies in pest management, wildlife conservation and livestock breeding.Read moreRead less
The makings of maleness: molecular and cellular functions of the Y-chromosomal sex-determining gene Sry. This project will reveal how the Y chromosome directs male development, identify steps that can go wrong, and suggest ways to diagnose and manage intersex conditions. It will also inform stem cell, pest management, wildlife conservation and livestock breeding technologies.