The Role Of The Zinc Finger Transcriptional Repressor Znf238 During Nerve Cell Maturation
Funder
National Health and Medical Research Council
Funding Amount
$394,264.00
Summary
Proper foetal brain assembly is critical for brain function, but the underlying genetic mechanisms remain poorly defined. In this study, I will investigate a family of proteins that “turn on” neural gene expression in combination with another protein that “turns off” their expression during nerve cell development. Understanding this novel on/off mechanism for controlling gene expression in newborn nerve cells will further our understanding of how the brain is assembled.
Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
Prenatal Origins And Health Outcomes Of Male Reproductive Congenital Anomalies Diagnosed At Birth And Testicular Cancer In Adulthood
Funder
National Health and Medical Research Council
Funding Amount
$234,343.00
Summary
There is growing concern in increasing male reproductive congenital anomalies diagnosed at birth & testicular cancer in adulthood. Research suggests these conditions share a common origin due to disruption in the release of male hormones in early pregnancy. This study will use a novel method of record-linkage to investigate maternal and infant risk factors and their combined effect on male reproductive disorders at birth and later in life; & assess long-term health and fertility of these males.
Characterisation Of Eurl, A Novel Gene Implicated In The Etiology Of Abnormal Brain Development And Intellectual Disability
Funder
National Health and Medical Research Council
Funding Amount
$597,541.00
Summary
Intellectual disability affects around one per cent of Australians, and can arise from genetic abnormalities during fetal life, such as through abnormal regulation of gene expression. We have identified a novel gene, known as eurl, which controls brain assembly as well as the ability of neurons to form functional connections within the brain. We will investigate how this novel gene controls brain development, and characterise eurl as a potential therapeutic target for learning and memory.
Mature red cells develop from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. We will determine the role of several molecules that interact with Lyn including Cbp, Liar and LACM, towards apects of red blood cell development.
Erythroid Molecular Cascades Involving The Tyrosine Kinase Lyn
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functio ....Mature red and white cells develope from hemopoietic stem cells in the adult bone marrow. The production of red blood cells is primarily controlled by the hormone erythropoietin (Epo). The availability of this hormone in a recombinant form has aided in the treatment of numerous forms of anaemia resulting from kidney failure, malignancies, and AIDS. Previously we had identified that the protein Lyn must be present inside primitive red blood cells for Epo to stimulate them to become mature functional cells. Recently, we have demonstrated that mice lacking the Lyn gene develope major problems with their red blood cells. We have identified several molecules which interact with Lyn in red blood cells. We have shown that a molecule called Cbp is important for Epo function in individual red blood cells and now we plan to investigate its function in whole animals. We have shown that a new molecule called Arp is important for red blood cell development. This protein moves in and out of the nucleus (where DNA is stored) and may be important in the regulation of genes needed for red blood cells. The third gene (AFAPbeta) is also novel and is closely related to another called AFAP-110, which can exert effects on the structure of a cell. Since red blood cells have to shrink considerably during their development, the role of AFAPbeta on red blood cell structure will also be investigated. From these experiments we should develop a much better understanding of how the production of red blood cells is controlled and how diseases of red blood cells (such as anaemia) occur.Read moreRead less
Sperm Competition and Sexual Selection. Competition between the sperm of two males within a single female has had profound implications for the evolution of male reproductive biology and behaviour. However, the reasons why females should mate with more than one male and thus generate sperm competition remains an evolutionary puzzle. Few studies have examined sperm competition from the female perspective and indeed, female perspectives are currently the subject of considerable debate. Using in ....Sperm Competition and Sexual Selection. Competition between the sperm of two males within a single female has had profound implications for the evolution of male reproductive biology and behaviour. However, the reasons why females should mate with more than one male and thus generate sperm competition remains an evolutionary puzzle. Few studies have examined sperm competition from the female perspective and indeed, female perspectives are currently the subject of considerable debate. Using insects as models I will examine the benefits of sperm competition for females and thereby the selective pressures that favour multiple mating. Moreover, I will determine whether sexual selection can act after copulation.Read moreRead less
Sperm competition and the evolution of ejaculates. This research will yield results that are at the cutting-edge in evolutionary biology, that will have a significant international impact, promoting the international profile of Australian science. The award will foster a world-class centre for research, and will train internationally competitive research scientists, adding to Australia's scientific capabilities. Through the development of IVF techniques in frogs, the research has the potential ....Sperm competition and the evolution of ejaculates. This research will yield results that are at the cutting-edge in evolutionary biology, that will have a significant international impact, promoting the international profile of Australian science. The award will foster a world-class centre for research, and will train internationally competitive research scientists, adding to Australia's scientific capabilities. Through the development of IVF techniques in frogs, the research has the potential to contribute to conservation outcomes for Australia's native frog fauna via captive breeding programs. The research groups connections with local infertility clinics has the potential to inform those studying human sperm in a time of growing concern over rising human infertility. Read moreRead less
The evolution of female mating frequency and its consequences. This project explores the evolutionary significance of female mating frequency for male and female reproductive biology. The research proposes to use innovative approaches to examine the evolution of ejaculate characteristics, will focus on the evolution of sperm form and function, and will examine the fitness benefits of promiscuity from the females' perspective. The research uses both vertebrates and invertebrates as model organi ....The evolution of female mating frequency and its consequences. This project explores the evolutionary significance of female mating frequency for male and female reproductive biology. The research proposes to use innovative approaches to examine the evolution of ejaculate characteristics, will focus on the evolution of sperm form and function, and will examine the fitness benefits of promiscuity from the females' perspective. The research uses both vertebrates and invertebrates as model organisms to test predictions and assumptions of theoretical models relevant to both internal and external modes of fertilization. The design of this project will allow cutting-edge, theoretically informed and experimentally grounded conclusions to be drawn regarding selection under sperm competition.Read moreRead less
Stroke outcomes directly relate to brain tissue rescue. We have contributed to changes in clinical practice through many clinical trials of new protocols and therapeutic strategies. Our program will focus on brain salvage in the pre-hospital setting and the acute hospital environment. We will use novel approaches to enhance brain recovery and design new implementation strategies to maximise the benefits of these therapeutic advances.