Professor Peter Koopman, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD.
Exactly 25 years have passed since the discovery of Sry, the Y-chromosomal gene responsible for directing male development in mammalian embryos. This landmark discovery in 20th century molecular genetics opened the door to detailed study of how genetic pathways channel the development of the initially bipotential embryonic gonads into testes and so generate phenotypic males. In this seminar I will describe the molecular and cellular events that direct testis differentiation, the steps that can falter resulting in disorders of sex development, and the increasingly vexed landscape of medical management of these conditions.
Our research focuses on genes that regulate sex development—the molecular process that determines whether an embryo develops as a male or a female—and finding how problems with these genes can cause intersex, infertility and testicular cancer.
We are studying SRY, the Y-chromosome maleness gene, and how it controls the genetic and cellular events leading to testis development and male sex determination. We also use molecular genetics tools to identify other sex development genes and to study how these affect sex development, using transgenic and gene-knockout mice to answer questions about gene function. Ultimately, we hope this research will help us to better understand the causes of human disorders of sex development, which affect up to 1 in every 250 children born each year, so that these disorders can be diagnosed more accurately and managed more effectively.
We are also interested in how germ cells—the embryonic precursor cells that become sperm in males or eggs in females—receive molecular signals from the testis or ovary in order to choose the corresponding path of sperm or egg development. We have discovered several signalling proteins that direct this decision and current research is focused on understanding how these signals act. This work is helping us find the causes of infertility and testicular cancer, two of the most common reproductive disorders whose incidence continues to rise.
More broadly, the study of embryo development provides insight into mechanisms of disease, including cancer, and provides a molecular and cellular basis for new molecular diagnostics and targeted therapies.