Elucidating The Cellular Processes That Are Critical For P53 Mediated Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$1,016,108.00
Summary
p53 is a tumour suppressor gene that is mutated in ~50% of human cancers. Mutations in p53 cause development of cancer and render malignant cells resistant to chemotherapy. We have identified genes regulated by p53 that appear critical for its tumour suppressive function. In this project, we will use innovative novel genetic tools to discover the cellular and biochemical functions of these genes. The ultimate goal of our studies is to identify novel targets for anti-cancer therapy.
Role Of MACROD2 Loss In DNA Repair, Chromosomal Instability And Development Of Colorectal Cancer: Clinical And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$772,871.00
Summary
The MACROD2 gene is deleted in one-third of human bowel cancers. We have discovered that MACROD2 deletion causes defective DNA repair and tumour chromosomal instability. Here, we will use novel laboratory models to show that MACROD2 loss actively promotes bowel cancer development. We will test the clinical implication of MACROD2 loss for predicting tumour therapy response and will investigate the potential of exploiting this deficiency for drug targeting.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
The Molecular Determinants Of Immunological Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Autoimmune diseases, such as type I diabetes and multiple sclerosis, are debilitating disorders that impose a massive toll on wellbeing in Australia and worldwide. This fellowship will support research aimed at determining the genes and mechanisms that control autoimmunity. New technologies will be brought to bear to track immune cells throughout their development, maturity and malfunction in disease settings. We aim to uncover new therapeutic targets to prevent and reverse autoimmune disease.
Methylation Sensitive Genes And The Transition To Allergic Disease: A Twin Study
Funder
National Health and Medical Research Council
Funding Amount
$493,843.00
Summary
Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in ....Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in children.Read moreRead less
Characterization Of HOXA-expressing Human Haematopoietic Cells Generated From Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$622,464.00
Summary
Blood stem cell transplants are used for treating a range of human blood disorders such as leukaemias. However, for many patients, suitable donors cannot be found. We are searching for ways in which embryonic stem cells can be turned into blood stem cells in the laboratory to provide a new source of these cells that could then be used to treat patients.
Transcriptional Regulation Of Definitive Hematopoietic Development In Humans
Funder
National Health and Medical Research Council
Funding Amount
$800,036.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells, such as human pluripotent stem cells. During development, blood cells are formed from the blood vessel wall, or endothelium. In this project, we will study the regulation of this process in order to more efficiently make human blood cells in the laboratory.
A Suite Of Engineered Human Pluripotent Stem Cell Lines To Facilitate The Generation Of Hematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$881,221.00
Summary
Our goal is to develop tools that address major bottlenecks that have prevented the generation of blood forming stem cells in culture for therapeutic use. We will generate human embryonic stem cell reporter lines that can be used to monitor key milestones in blood stem cell development. These lines will serve as tools to identify growth conditions to improve the differentiation of pluripotent stem cells to functional blood stem cells.
Generating Haematopoietic Stem Cells From Human Pluripotent Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$872,215.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells. Using a new approach that we have developed, our laboratories will make blood stem cells from human pluripotent stem cells that will treat patients needing a transplant.
The Mezzanine T Cell Response: Intervening At The Coal Face
Funder
National Health and Medical Research Council
Funding Amount
$765,585.00
Summary
In an initial immune response, specialised cells in lymph nodes tell T cells to multiply; the stimulated T cells depart and enter target tissue (e.g. lung in the case of flu). We describe a new response whereby the target tissue itself can tell T cells to multiply further. This response in target tissues reveals a new way of altering immune responses. This is especially important as in many diseases, the primary lymph node response has already occurred, so cannot be therapeutically intervened.