Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102263
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Export of effector proteins by P. falciparum to the infected red blood cell. Infection by the malaria parasite has lethal consequences for humans. The parasite exports hundreds of proteins via a translocon to commandeer the red blood cell. This project aims to determine the function of one of the major translocon components and determine if it is a viable target for anti-malarial drug development.
Studying precancerous stem cells that cause T cell leukaemia. Recent research has identified abnormal stem cells that are the cause of T cell leukaemia. They are also resistant to therapeutics suggesting that they could be a cause of relapse. The aim of this project is to determine the abnormal pathways that cause these cells to become immortal and to determine new therapeutic strategies to eliminate them.
Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and de ....Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and degenerative diseases. Also, a strong bridge will be built upon the previous collaborations of the research teams in Brisbane and Pennsylvania, which will facilitate advanced teaching and training of Australian PhD and post-doctoral scientists.Read moreRead less
Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthes ....Development of Model Systems to Investigate Blood Hydrodynamic Parameters Affecting Blood Cell Function: An Interdisciplinary Approach. National benefit will come through this research contributing to a better understanding of blood flow biology and pathology, both of which are of particular relevance to the aging Australian population. This benefit is well aligned with the 2008 National research priority 2: Promoting and Maintaining Good Health; Priority Goal 3. Preventative Health. The synthesis of both extensive expertise in platelet/cardiovascular research and bioengineering/rheology should provide a substantial platform from which fundamental new discoveries in this niche area can be made. The development of novel platelet analysis tools arising from this work may also ultimately lead to new intellectual property and attract industry based funding.Read moreRead less
Short silk nanofibre based 3D scaffolds with enhanced biomimicry. This project aims to understand the behaviour of haematopoietic stem cells (HSC) in novel 3D scaffolds based on short silk nanofibres. This will lead to highly functional 3D scaffolding materials that support efficient HSC renewal in vitro. This project aims to overcome the key problem with existing in vitro systems, which lack the morphological and biochemical complexities of native HSC-niche. Since haematopoietic stem cells are ....Short silk nanofibre based 3D scaffolds with enhanced biomimicry. This project aims to understand the behaviour of haematopoietic stem cells (HSC) in novel 3D scaffolds based on short silk nanofibres. This will lead to highly functional 3D scaffolding materials that support efficient HSC renewal in vitro. This project aims to overcome the key problem with existing in vitro systems, which lack the morphological and biochemical complexities of native HSC-niche. Since haematopoietic stem cells are the precursors to all blood cells, this project has the potential of engineering a high yield artificial ‘blood factory’, which will help save the lives of many thousands of people who rely on bone marrow transplants to treat life-threatening illness such as leukaemia.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100106
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
An advanced flow cytometry facility for the Peter Doherty Institute. The establishment of a flow cytometry facility in the new Peter Doherty Institute for Infection and Immunity will enhance capacity to investigate immunity to a broad range of very serious diseases. This project will support researchers studying viral and bacterial infection as well as cancer and autoimmunity.
Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal c ....Role of the PU.1 transcription factor in regulating lymphoid development. Haemopoiesis is a tightly regulated process and provides an important model for our understanding and application of stem cell biology. Perturbation of early haemopoiesis results in a number of important disorders including leukaemia, anaemia and immunodeficiency. The application of stem cells to many disease conditions is currently being pursued, however, in order to develop therapeutic interventions knowledge of normal cellular differentiation is crucial. The studies outlined here aim to contribute to the understanding of the these processes and hence help to provide the framework for future studies aimed at more directly altering cell fate decision for clinical applications. Read moreRead less
Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preven ....Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preventative health perspective, the investigation of platelet calcium signalling will greatly accelerate the development of new pharmaceuticals to tackle acute and chronic cardiovascular diseases, such as stroke, heart attack and artherosclerosis. Read moreRead less
Inhibiting pathological signalling in haematopoietic disease. Certain leukaemias and other blood diseases are caused by the mutation of one particular molecule, called Janus Kinase (JAK), inside our bodies. This project aims to understand the biochemical details of these diseases by studying this mutated molecule in detail. The project will aim to provide the information for developing effective therapeutics against these diseases.