Hormone-dependent Autophagy And Growth Signalling In Developmental Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$613,447.00
Summary
Cell death is essential for cell and tissue homeostasis and its dysregulation is associated with many diseases. We discovered a new mode of cell death that involves autophagy. We have now identified that TGF-? signalling pathway, which has roles in numerous human pathologies, is involved in autophagy-dependent cell death. Our proposed studies will further characterise this important signalling axis and study its significance in development, normal physiology and disease.
The Role Of Scube Gene Function In Hedgehog Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
The Hedgehog signaling pathway controls development of the early embryo and is one of the most common pathways mutated in human cancer. Through the use of zebrafish genetics we have identified a new component of this pathway, Scube2 that controls the ability of cells to be activated by Hedgehog signaling. We plan to further investigate how this occurs and design therapeutically relevant peptides based on the scube2 protein that could act as inhibitors of the pathway
Control Of Germline Progenitor Cell Fate And Fertility By The MTORC1 Signaling Pathway
Funder
National Health and Medical Research Council
Funding Amount
$563,798.00
Summary
Maintenance and repair of many adult tissues is dependent on a rare population of stem cells. Germline stem cells are essential for male fertility although the mechanisms controlling these cells are poorly understood. We have identified a key role for the growth-promoting mTORC1 pathway in regulation of germline stem cell function. Our studies of upstream regulators and downstream targets of this pathway in germline cells promise unique insight into infertility, tissue regeneration and cancer.
Understanding The Regulation Of Kidney Morphogenesis In Order To Improve Renal Development
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be in ....Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be influenced.Read moreRead less
Control Of Organ Size And Cancer By The Hippo Pathway
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Hippo pathway controls tissue growth and cancer. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Genetic Control Of Body Patterning: Intersection Of Transcriptional And Signalling Activity In Head Formation
Funder
National Health and Medical Research Council
Funding Amount
$579,932.00
Summary
A most critical step in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. The objective of our research is to understand how the mechanisms that control genetic activity and cell-to-cell signalling may cooperate in the formation of the head and face of the embryo. The outcome will focus future clinical investigations to the most relevant genetic determinants of craniofacial defects.
The Role Of Ten-m3 In Patterning Ipsilateral Retinal Projections
Funder
National Health and Medical Research Council
Funding Amount
$453,042.00
Summary
The normal functioning of the brain depends on connections of billions of nerve cells or neurons. We have found that a protein called Ten_m3 plays a very important role in specifying the way that neurons from the eye connect to the brain. The role of this protein is so important that mice which lack the protein behave as if they are blind. The aim of this project is to understand how this protein controls the development of the visual system.
Trajectories Between Childhood Internalising Behaviour Problems And Adolescent Depressive Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$55,000.00
Summary
Depressive symptoms are known to escalate sharply through the adolescent years. Adolescents who experience an episode of depression are very likely to experience further mental illness as adults. Efforts to prevent depressive illness may be advanced by research delineating the factors and processes implicated in the early emergence of depressive symptoms. To advance such an understanding this project will analyse data collected, in part, through NHMRC support to Australian Temperament Project (A ....Depressive symptoms are known to escalate sharply through the adolescent years. Adolescents who experience an episode of depression are very likely to experience further mental illness as adults. Efforts to prevent depressive illness may be advanced by research delineating the factors and processes implicated in the early emergence of depressive symptoms. To advance such an understanding this project will analyse data collected, in part, through NHMRC support to Australian Temperament Project (ATP) researchers. The ATP data will be used to examine factors associated with the development and progression of depressive symptoms from childhood to adolescence. The ATP data set includes detailed longitudinal data collected from multiple sources (parents, teachers and youth) concerning child and adolescent temperament, behavioural problems, mother-child relations, health, depressive symptoms, school achievement, school adjustment, social skills, peer relationships, parenting practices, stressful life events, and sociodemographic factors. Of an original sample of 2443 enrolled in the cohort in 1983 (aged 4-8 months) a subsample of 1,350 adolescents should complete the data collection due in 2000 (age 17-18). Through the analysis of ATP data proposed in this application, models will be developed to explain the risk and resiliency processes in childhood and early adolescence influencing the development and course of adolescent depression, for different subgroups of adolescents. To achieve this objective, analyses will: 1. identify groups who have differing trajectories from childhood internalising behaviour problems to adolescent depressive symptoms; 2. compare groups to identify factors that contribute to the progression from internalising behaviour problems to depressive symptoms, while also identifying factors which appear to impede such progression and; 3. compare groups to identify factors associated with transient versus persistent depressive symptoms in adolescence.Read moreRead less
Signalling And Transcriptional Activity For Craniofacial Morphogenesis In An Experimental Genetic Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$74,755.00
Summary
Abnormalities in craniofacial development affect 2-1000 births in Australia. The aim of this project is to identify genes crucial for the development of the head and face. In particular the project focuses on the Twist1 gene. TWIST1 plays a key role in craniofacial development and individuals lacking functional Twist1display facial anomalies such as craniosynostosis and cleft palate. Dissecting the function of Twist1 is essential to identifying new avenues for the prevention of these defects.
Wnt-Ryk Signaling In The Establishment Of Major Axon Tracts In The Embryonic Mouse Brain
Funder
National Health and Medical Research Council
Funding Amount
$513,946.00
Summary
The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanism ....The corpus callosum is the major interhemispheric commissure in the human brain, comprising approximately 3 million myelinated fibers which connect homologous regions in the neocortex. To date more than 50 different human congenital syndromes have been described in which the corpus callosum does not form leading to epilepsy and mental retardation. We have identified a new guidance molecule (Ryk) which is crucial for corpus callosum formation. This project aims to dissect that molecular mechanisms controlling Ryk signaling during corpus callosum development. Our analysis of Ryk function will advance our understanding of the molecular mechanisms underlying the formation of this important commissure.Read moreRead less