Understanding The Role Of Three-dimensional Genome Organisation In B Cell Lineage Commitment And Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Every one of your nuclei contain 2 metres of DNA. This DNA is 300,000 times longer than the nucleus itself. In order to fit into this space, while maintaining access to crucial genes, the DNA forms a fantastically ordered three-dimensional structure. This intricate organisation is crucial to health, with even minute changes driving diseases, such as cancer and heart disease. We propose using new technology to understand how this organisation changes during immune cell development and leukaemia.
Role Of Common Genetic Variation Driving Single Cell Transcriptional Heterogeneity Across The Cardiomyocyte Lineage
Funder
National Health and Medical Research Council
Funding Amount
$882,698.00
Summary
In human tissues, most mature cells develop by differentiation from pluripotent stem cells. As they undergo differentiation, their transcriptional activity changes dramatically. Many of the genetic causes for these changes are unknown, which limits research in the use of stem cells for treating and modelling disease. This proposal addresses this problem with cardiac muscle cell differentiation by utilising recent developments in biotechnology that enables individual cells to be sequenced.
Characterisation Of Novel Regulators Of The Haemopoeitic System.
Funder
National Health and Medical Research Council
Funding Amount
$381,680.00
Summary
All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature ce ....All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature cells, however, that have changed pathways. We have use one of these, the mouse J2E red cell changing into macrophages, to identify the genes involved in this process. Two of the genes we found, HLS5 and HLS7, are potentially important in lineage determination and normal blood development as well as the formation of blood cancers. This project aims to investigate the roles these genes play in blood development. Much of our work to date has focused on HLS7. The human equivalent of HLS7 was found by an American group independently of us as a gene which causes one type of blood cancer. We have shown HLS7 has dramatic effects on normal blood development and, together, these results clearly show the importance of this gene. Through our studies on how HLS7 works, we have identified another gene, M44, which may be important in regulation of HLS7 and also plan to investigate is function. Finally, HLS5 has similarities to a group of molecules called transcription factors which are known to be key regulators blood development. Clearly, analysis of this gene will further our knowledge in this field.Read moreRead less
Structure And Composition Of The Pre-T Cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
In order to recognize a wide variety of pathogens, humans produce many different T cell receptors (TCRs) by the process of gene-rearrangement. However, gene-rearrangement may not always lead to a functioning TCR. We are studying the pre-TCR protein that is responsible for monitoring the success of gene-rearrangement and is thus essential for the formation of a robust immune system. Understanding pre-TCR function will lead to new treatments for immune related diseases.
A Study To Evaluate Safety And Feasibility Of Administrating Zoledronic Acid To Children And Adolescents With Acute Lymphoblastic Leukemia And Lymphoma To Prevent Joint Complication.
Funder
National Health and Medical Research Council
Funding Amount
$16,231.00
Summary
Osteonecrosis (bone death) is a debilitating complication seen following chemotherapy for acute lymphoblastic leukemia in older children. It potentially could lead to destruction of joint, severely limiting quality of life and ultimately requiring joint replacement surgery. Currently there is no effective medical treatment to manage this. Based on our animal experiments we want to study if Zoledronic acid could prevent severe joint destruction in these children and improve their quality of life.