Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorde ....Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases world-wide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing fetus, fetal hemoglobin. We have identified a key factor important for fetal gene expression. We will now determine whether manipulation of this factor can cure hemoglobin disorders.Read moreRead less
A Novel Genetic Element Controlling Adult Hemoglobin Production
Funder
National Health and Medical Research Council
Funding Amount
$493,907.00
Summary
Disorders of the blood protein hemoglobin are the commonest genetic diseases worldwide, and include thalassemia and sickle cell disease. In this proposal we study two novel mouse lines that exhibit thalassemia, but lack any of the known genetic mutations that cause this disease. These mice afford us the opportunity to make unique observations into how hemoglobin is produced, and thereby provide a platform for new therapeutic approaches in these devastating diseases of the blood.
Sickle cell anaemia and ?-thalassaemia are debilitating diseases for which there is no effective treatment. Patients require lifetime blood transfusions and drugs with significant side effects. These diseases are ameliorated in patients that express foetal haemoglobin into adulthood. The goal of this research is to understand how foetal haemoglobin is normally turned off at birth. This will ultimately help us discover how to switch it back on to treat patients.
A Mechanotransduction Apparatus To Coordinate Epithelial Collective Cell Migration.
Funder
National Health and Medical Research Council
Funding Amount
$994,596.00
Summary
Epithelial cells migrate as physically coherent collective groups, which is necessary for normal development and is disrupted as cancers progress to become invasive and spread. Collective migration requires communication so that the behaviour of individual cells is properly coordinated. In this project we investigate how the transmission of physical force between cells allows them to communicate; and test how its disruption contributes to cancer invasion.
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
Regulation Of T Cell Effector Function In Peripheral Tissues
Funder
National Health and Medical Research Council
Funding Amount
$698,550.00
Summary
Protection from infections relies on different types of immune cells. While some of these cells are found in the blood, others reside in peripheral tissues such as the skin. We will analyse the function of these peripheral immune cells to understand how they work to fight off infections. We will also investigate how so-called memory cells that permanently reside in peripheral tissues can protect from re-infection with similar bacteria or viruses.
The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
The Molecular And Cellular Trajectories Of Clonal Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$826,742.00
Summary
Dendritic cells (DCs) are a blood cell type with a crucial role in our immune system. They are made in the bone marrow from stem and progenitor cells. How each of these cells individually makes DCs is complex and dynamic. We seek to understand this using cutting edge technologies to track each cell’s step-by-step role in this important process. This knowledge may help the use of DCs in the treatment of several diseases including autoimmunity and cancer.
Deciphering The Role Of Scribble In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$628,789.00
Summary
Scribble is a protein that controls the orientation and organization of all cells within our body. Mutations in the Scribble gene are found in many cancers and also in some patients with spina bifida, however how these mutations cause these diseases is not understood. Here we propose experiments that can be used to link Scribble mutations to specific cellular functions. This information will help us design new therapies to treat diseases driven by tissue disorganization such as cancer.
Identifying The Ontogeny And Fate Of T Follicular Helper Cells By Two-photon Photoconversion
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vacc ....The aim of this proposal is to investigate immune cells called T follicular helper cells using a novel microscopy-based method that we have developed. This method lets us ‘tag’ these cells in a way that enables us to distinguish them from all other cells and follow them as they migrate to different immunological compartments during the response. T follicular helper cells are important for protective immune responses against pathogens and a better understanding of this T cell subset will aid vaccine design.Read moreRead less