Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$4,580,898.00
Summary
Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo ....Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research program will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans. Australia boasts three of the foremost international researchers in sex determination. Their contributions have been fundamental to the advancement of the field, including the identification and characterization of the master testis determining gene and other genes critical for sex determination. They now propose to pool their expertise in human molecular genetics, mouse developmental biology and protein chemistry to bring spectacular advances in our knowledge of human sexual development and its associated disorders. This information will be used to bring improved clinical care to patients withdisorders of sexual development.Read moreRead less
My background is in the study of human molecular genetic disease, and my interest has evolved to the analysis of embryonic development using the mouse as a model system. My particular interest is in the molecular mechanisms governing limb and craniofacial
We will apply genome-wide approaches to identify the gene networks that regulate the self-renewal and the differentiation of muscle stem cells and their fusion to muscle fibres. These studies will deliver the first characterisation of the molecules and pathways implicated in these processes, which are essential steps of muscle growth.
Analysis Of Gene Regulation In Disorders Of Sex Development
Funder
National Health and Medical Research Council
Funding Amount
$524,852.00
Summary
Disorders of Sex Development (DSD) are surprisingly common, however the majority of cases still cannot be explained. Our hypothesis is that a significant proportion of DSD is due to disturbed gene regulation. We will use state of the art methods to analyse the regulation of DSD genes. Our research will improve our knowledge of the regulation of genes that affect DSD and provide a diagnosis for DSD patients for whom the underlying cause is unknown. This in turn will improve clinical management.
Disorders of sex development (DSDs) are surprisingly common, and often result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. This research combines expertise in human molecular genetics, mouse developmental biology and protein chemistry to identify genes important for sex determination and development of the gonads, and discover how they contribute to DSD, in order to improve clinical care to patients with DSD.
Disorders Of Sex Development: Genetics, Diagnosis, Informing Clinical Care
Funder
National Health and Medical Research Council
Funding Amount
$5,751,502.00
Summary
Disorders of sexual development (DSDs) are surprisingly common, and often result in genital abnormalities, gender mis-assignment, infertility and psychological trauma. We will pool our expertise in human genetics, molecular and developmental biology, to find genes important for sex development, identify gene defects that cause DSD, and study their functions. We will liaise with clinicians to apply these findings to the accurate diagnosis and medical care of DSD in children.
Muscle Fusion Defects May Be A Common Cause Of Human Dystrophies
Funder
National Health and Medical Research Council
Funding Amount
$391,419.00
Summary
While muscle fusion is a crucial step of muscle formation, it is surprising that human muscle diseases were never associated with muscle fusion defects. We have recently undertaken a genome-wide functional screen using a mouse muscle cell line. We identified 21 genes that were previously associated with muscle dystrophies in human. The aim of this project is to examine the role of those genes during muscle fusion in vivo, using the chick embryo, mouse mutants and lines from patients as models.
Birth defects can have devastating consequences for individuals and their families, and improving our ability to diagnose and screen for these disorders has implications for treatment and reproductive options. We are using the mouse as a model to discover genes important in a new class of birth defects caused by dysfunction of a hair-like cellular projection known as the cilium.
Hedgehog Signalling In Limb And Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,544.00
Summary
Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in b ....Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in both limb and face development. Based on the organs in which our genes of interest are active, we believe that they will also play key roles in embryonic development of the limbs, face and other organs. We now plan to investigate the regulation of a subset of these genes based on analysis in mouse models of limb and face development. In addition, we have chosen to further analyse the function of a completely novel gene we have identified which our preliminary studies suggest may play a role in the normal development of the lip and palate. These studies have the potential to shed light on the processes governing how organs develop, as well as on the molecular basis of common birth defects such as polydactyly (extra fingers and toes) and cleft palate.Read moreRead less
Interaction Between Moz And PRC1 In Defining Epigenetic States And Gene Expression Patterns
Funder
National Health and Medical Research Council
Funding Amount
$427,271.00
Summary
Regulation of gene expression is implicated in all disease processes. Aberrant gene expression is particularly associated with tumour formation. In this project we determine the relationship between an oncogene MOZ and another oncogene BMI1. Together these proteins regulate one of the most important systems controlling gene expression at the level of chromatin structure.