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.
Epigenetic Regulation Of Self-renewal Signalling Pathway In Leukemic Stem Cell Formation
Funder
National Health and Medical Research Council
Funding Amount
$885,476.00
Summary
Acute myeloid leukaemia (AML) is a fatal form of blood cancer. The survival of patients with AML remains poor and this is due to the return of disease after chemotherapy (relapse). Leukemic stem cells (LSCs) are the major cause of relapse and we study how LSCs are regulated. This will provide valuable input into the development of novel therapeutic strategies to target therapy-resistant LSCs and improve AML outcome.
Investigating The Roles Of The Wnt And Notch Signalling Systems In Colon Cancer Crypt Biology
Funder
National Health and Medical Research Council
Funding Amount
$604,439.00
Summary
Colon cancer occurs because of mutations to a tumour suppressor gene. These mutations alter the growth and positional signals for the cancer cells. This project aims to produce a computer model of the regulatory processes in normal colonic cells, to discover why the mutations lead to cancer and to discover rational drug targets for interfering with the growth of colon cancer cells.
(Re)wiring A Stem Cell: Deciphering The Molecular Mechanism Underpinning Lineage Propensity
Funder
National Health and Medical Research Council
Funding Amount
$855,780.00
Summary
This project explores the response of the stem cells to cues that direct how they turn into specific type of cells that is suitable for clinical use. Specifically, a set of driver genes whose activity can foretell the outcome of cell differentiation will be identified. By modulating the maintenance conditions, iPSCs lines may be tailored for specific applications in stem cell therapy and disease modelling for the assessment of treatment efficacy.
The immune system must be tightly regulated to make sure that it makes the right response to effectively fight off infection whilst avoiding inappropriate responses that cause damage such as in autoimmunity, inflammation or allergy. This project studies patients who have genetic defects that affect their immune systems and make them susceptible to infection and/or harmful immune responses. This will reveal some of the critical signals that maintain immune control.
Aberrant Ependymal Development And The Formation Of Hydrocephalus
Funder
National Health and Medical Research Council
Funding Amount
$660,005.00
Summary
Foetal hydrocephalus is a prevalent neurodevelopmental condition associated with severe intellectual impairment. Breakdown of the ependymal cell layer, which acts as a barrier between brain tissue and the ventricular space, is a major cause of hydrocephalus. Despite the importance of these cells, we have little understanding of the molecular mechanisms that regulate their production. This project will identify critical signalling pathways governing the establishment of the ependymal layer.
Molecular Determinants Of Advanced Disease In Ovarian Granulosa Cell Tumours
Funder
National Health and Medical Research Council
Funding Amount
$612,244.00
Summary
Granulosa cell tumours of the ovary (GCT) represent 5-10% of malignant ovarian cancers. They are distinct from the more common epithelial tumours and although considered to have a much better prognosis, they have a propensity to late recurrence. Recurrent or aggressive GCT have a poor prognosis. These studies will investigate the molecular basis of recurrence and aggressive behaviour in GCT. This will provide both prognostic information and also potential therapeutic targets.
Translating Molecular Insights In Squamous Cell Carcinoma Into Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$859,551.00
Summary
In Australia, skin cancers account for 80% of all new cases of cancer, and over 95% of these are basal cell cancers (BCC) or squamous cell cancers (SCC). Although exposure to the sun is the major factor responsible for both of these cancers, it is not known what genes are damaged allowing them to grow in an uncontrolled manner. Our laboratory has identified critical genes that malfunction in SCC. This discovery will allow us to develop new preventative and curative strategies for SCC.
Each year, 18,000 Australian men are diagnosed with prostate cancer. While current treatments are designed to directly target cancer cells, the tumour-associated stroma is also recognised to play a pivotal in the establishment and progression of prostate cancer. This grant aims to investigate the contribution of stromal Hedgehog signalling, with the view to creating new treatment strategies that will treat the entire tumor environment.
Defining The Role Of Nedd4 In Neural Crest Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$541,565.00
Summary
Neural crest cells are specialised stem cells that give rise to many tissues and organs during embryonic development. We recently identified an essential role for a regulatory protein in neural crest cells. Our research is aimed at understanding how this protein influences the growth of structures such as the heart and facial skeleton. Understanding these processes underpins the ultimate goal of implementing diagnostic and preventative medicine for highly prevalent congenital birth defects.