Sex Determination and Disorders of Sex Development
One of the most amazing biological processes is the development of a fertilized egg into a complex organism. It involves the orchestration of cellular processes, which is controlled by a delicate network of gene regulation. Disturbance of this network during development results in malformation and malfunction of organs, diseases such as cancer, and often lethality. Our laboratory studies mechanisms of gene regulation during embryonic development focussing on the development of embryonic gonads and their related disorders using mouse as a model system.
Disorders/differences of sex development (DSDs) refer to congenital conditions in which the development of chromosomal, gonadal or anatomical sex is atypical. They are very common, with an estimate of approximately 1 in 4,500 births. They have profound psychological and reproductive consequences for the patient, which are also often prone to testicular or ovarian cancer later in life. Surprisingly, although many genes have been identified which play a role in these processes for almost 70% of cases we still do not know the underlying cause. Clearly, the identification of new genes and regulatory mechanisms involved in the formation of testis and ovary is critical for understanding the molecular pathology of DSDs.
Project 1: The influence of a ketogenic diet on female fertility
Supervisors: Dr Dagmar Wilhelm, Dr Stefan Bagheri-Fam, Prof David Gardner
A ketogenic diet (high fat, normal protein, low or no carbohydrate) has become very popular to lose weight. However, we have preliminary data that consummation of this diet leads to impaired female fertility. This project investigates the cellular and molecular mechanisms that lead to reduced female fertility using mouse as a model system..
The prorenin receptor is best known for its role in the renin-angiotensin system (RAS). However, recent research also shows that it plays multiple crucial roles independent of pro/renin binding, including WNT and MAPK signalling, receptor recycling and autophagy. We have shown that loss of the prorenin receptor in mouse somatic cells of the gonads results in female infertility. This project characterizes its role in ovarian development and function using mouse as model system.
The prorenin receptor is best known for its role in the renin-angiotensin system (RAS). However, recent research also shows that it plays multiple crucial roles independent of pro/renin binding, including WNT and MAPK signalling, receptor recycling and autophagy. We have shown that loss of the prorenin receptor in mouse somatic cells of the gonads results in male and female infertility. This project takes advantage of the fact that the prorenin receptor is highly conserved between mammals and flies, offering the opportunity to elucidate the molecular mechanisms of PRR function in gonads using Drosophila as a model system.