GTPase Regulation Of The Hippo Organ Size-control Pathway
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
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 two proteins, Pix and Git, control tissue growth by regulating the Hippo pathway. These studies will be performed in flies. 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.
Mechanisms Regulating The Levels Of Circulating Insulin In Response To Nutrition
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Diabetes is the fastest growing chronic disease both in Australia and worldwide, caused by the failure of cells within the pancreas to produce sufficient insulin. I aim to determine how different nutritional inputs alter the levels of circulating insulin, and identify and characterise genes required for insulin production and secretion. As well as providing important insights into the mechanisms that regulate insulin secretion, I will identify new therapeutic targets for diabetes treatment.
Defining The Molecular Effectors Of Gene/environment Interaction On Mouse Heart Development
Funder
National Health and Medical Research Council
Funding Amount
$749,271.00
Summary
One third of all birth defects involve the heart, and are the most common cause of infant death. Some defects are due to genetic factors, but others arise when the pregnant mother is exposed to environmental stress. We will examine how one stress (low oxygen levels) causes abnormal heart formation in the embryo, look at what causes this at a molecular level, and explore if such stress increases the risk of heart defects in families with a history of such abnormalities
Role Of The LIM-only Protein LMO4 In Lung Development And Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$490,395.00
Summary
Lung cancer is the leading cause of death in cancer patients in Australia. Although treatments have improved in the past 10 years, new therapeutic strategies are eagerly awaited. Deregulation of molecules driving development of normal tissue is often observed in cancer. Our aim is to identify key regulators of lung development and lung repair after injury. We aim to evaluate the role of these molecules in the initiation and progression of lung cancer to identify new targets for therapies.
Coupling The Mechanical, Signalling And Transcriptional Mechanisms That Initiate Pathogenesis Of Cerebral Cavernous Malformation
Funder
National Health and Medical Research Council
Funding Amount
$1,228,364.00
Summary
Cerebral cavernous malformations (CCMs) are thin walled, vascular malformations in the brain found in 1/200-250 individuals. They can cause migraine, neurological deficits or stroke. This disease can be inherited due to damaging mutations in any of three CCM genes. The project will investigate the molecular control of CCM pathogenesis in animal models. We aim to uncover the molecular cause of these vascular malformations and in doing so identify new therapeutic strategies.
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.
Investigating The Role Of The Notch4 Receptor In Blood Vessel Formation And Remodelling In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$653,086.00
Summary
We aim to understand how blood vessels form. This process is crucial for foetal development, and for injury repair in adults. When there is too much or too little blood vessel formation, diseases such as arthritis, blindness and osteoporosis can result. Also many tumours grow and spread by growing new blood vessels. We will study a signal that occurs between cells (Notch signalling) that is important in controlling the amount of blood vessel formation, by analysing in detail one component (Notch ....We aim to understand how blood vessels form. This process is crucial for foetal development, and for injury repair in adults. When there is too much or too little blood vessel formation, diseases such as arthritis, blindness and osteoporosis can result. Also many tumours grow and spread by growing new blood vessels. We will study a signal that occurs between cells (Notch signalling) that is important in controlling the amount of blood vessel formation, by analysing in detail one component (Notch4)Read moreRead less
Fibroblast Growth Factor Receptor 2c And Human Testicular Dysgenesis
Funder
National Health and Medical Research Council
Funding Amount
$611,197.00
Summary
Disorders of sex development (DSD) account for 7.5% of all birth defects. DSDs that affect testis development lead to testicular tumours, ambiguous genitalia, male-to-female sex reversal, and infertility. We have identified a novel protein (FGFR2) essential for testis development in mice and found the first FGFR2 mutations in DSD patients with testicular dysgenesis. Understanding the molecular action of FGFR2 will lead to improved diagnosis and management of DSD.
Nodal Signalling In Male Germ Cell Development: Balancing Fertility And Testicular Cancer Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$536,595.00
Summary
Testicular cancer is the most common type of cancer in men aged 20-40 years, and its incidence has doubled in the last 30 years. It is sometimes fetal and often results in infertility. We have discovered new genes that regulate testicular cell behaviour in the developing fetus, and here test the concept that defects in these genes might disrupt cell behaviour to the point where cancers form during adult life. Outcomes may lead to new ways to diagnose and treat testicular cancers.