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.
The Role Of Growth Factors In Pluripotency And Differentiation Of Human Embryonic Stem Cells Towards Human Therapy
Funder
National Health and Medical Research Council
Funding Amount
$380,829.00
Summary
Human stem cells, obtained and studied within strict ethical guidelines, have huge potential for increasing our understanding of early human development and for transplantation therapy. In order to realise this potential the factors that maintain these cells as stem cells (able to divide indefinitely and to become any cell type) and which turn them into particular cell types must be understood. This project aims to study these factors and to apply stem cells to muscle disease therapy.
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.
Regulation Of The Drosophila C-Myc Homologue In Stem Cell Growth And Division.
Funder
National Health and Medical Research Council
Funding Amount
$613,397.00
Summary
The mechanisms controlling stem cell growth and division require elucidation if we are to use stem cells in regenerative medicine and find cancer treatments. Due to experimental limitations such mechanisms are largely unknown in humans. We aim to use the vinegar fly as a model system to understand the importance of microenvironment to cancer gene control in stem cells. We will identify the secreted signals, from the neighbouring cells, required to control cancer initiation in stem 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.