Defining The In Vivo Contribution Of Leukocyte Extracellular Traps To Infective Disease
Funder
National Health and Medical Research Council
Funding Amount
$598,363.00
Summary
Neutrophils are the white blood cells that protect against infection. A surprising protective neutrophil behaviour was recently described – neutrophils can pack up their internal DNA and antimicrobial enzymes and explosively release them into their surrounds, forming a “Neutrophil Extracellular Trap” (NET). This project uses zebrafish built have fluorescent neutrophils to study NET release in living animals. We will learn how NETs control infection and what goes wrong when NETs cause disease.
Studies Of Myeloid Leukaemogenesis In The Zebrafish
Funder
National Health and Medical Research Council
Funding Amount
$171,827.00
Summary
This project aims to investigate the causes of white blood cell cancer, or leukaemia, at the molecular level, using a novel approach in zebrafish. Zebrafish provide a powerful experimental model for developmental genetics, largely due to the visual and technical accessibility of embryos for experimentation. We plan to introduce a fluorescent molecular tag into the white blood cells in order to directly visualise them. We will then predispose these fish to leukaemia and screen for mutants with en ....This project aims to investigate the causes of white blood cell cancer, or leukaemia, at the molecular level, using a novel approach in zebrafish. Zebrafish provide a powerful experimental model for developmental genetics, largely due to the visual and technical accessibility of embryos for experimentation. We plan to introduce a fluorescent molecular tag into the white blood cells in order to directly visualise them. We will then predispose these fish to leukaemia and screen for mutants with enhanced or suppressed leukaemia. We anticipate that the mutants will allow new genes involved in the development of leukaemia to be identified.Read moreRead less
Cellular And Molecular Mechanisms Of Fungal Infection Pathogenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
Fungal infections are serious problems for patients with depressed immunity such as chemotherapy or transplant patients. More effective antifungal treatments are needed. We will study a model of fungal infection in zebrafish embryos that recapitulates human penicilliosis. The research will study how the infection establishes and how different types of white blood cells either help or hinder infection establishment. The results will point to new approaches for treating serious fungal infections.
Zbtb11 is a druggable protein that is mis-expressed in blood cancers - second biggest cause of cancer death in Australia - and liver cancer, third leading cause of death from cancer worldwide. We have found that it interacts with 2 other proteins with potential roles in these diseases. Our studies examine the nature of these Zbtb11-partner interactions and their particular consequences for blood disorders. Zbtb11 contributions to disease development will be a target for novel disease therapy.
Modelling Haematopoietic Disease And Leukocyte Function Using Zebrafish Models
Funder
National Health and Medical Research Council
Funding Amount
$686,656.00
Summary
Dr Lieschke studies white blood cell function and diseases. His biomedical research uses zebrafish animal models of human white blood cell diseases and he is an international expert on their blood and immune systems. His current research aims to understand what goes wrong in diseases when there are too many white blood cells (as in leukaemia), or too few (as in some hereditary diseases), and to develop new therapies for controlling inflammatory and infective diseases.
The Role Of Med12, A Subunit Of RNA Polymerase II Mediator, In Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$495,490.00
Summary
In a screen of zebrafish for mutations in blood cell development, we isolated a mutant called syrah. The mutation causing the blood defect was identified in a gene called med12, which encodes a component of the RNA transcription machinery in cells. To understand how this mutation causes a reduction in blood cells, we will identify the proteins that interact with the med12 protein. Understanding the pathway involved may lead to the discovery of new causes of human congenital blood diseases.