Development Of Endogenous Granulocyte Colony Stimulating Factor (G-CSF) Antagonism As A New Therapeutic Approach To Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$401,561.00
Summary
Neutrophils play a pivotal role in inflammatory diseases including rheumatoid arthritis (RA). G-CSF is a growth factor that is important to neutrophil survival and function. We have shown that in the absence of G-CSF the incidence and severity of experimental autoimmune arthritis are reduced. We will investigate the mechanisms by which this occurs as well as studying the effects of G-CSF blockade on function and survival of human neutrophils from healthy donors and RA patients.
Control Of TGF-beta Superfamily Signalling In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Members of the transforming growth factor ? (TGF-?) family of proteins play crucial roles in adult tissue homeostasis. In recent years a new paradigm has emerged suggesting that inhibition of TGF-? signalling could be an effective strategy for restoring homeostasis in disease-affected tissues. Dr Harrison’s overall research strategy is based on this concept, and is particularly focussed on developing specific antagonists of individual TGF-? proteins.
Nerve cell survival is dependent on both growth-promoting factors and factors released by neurotransmission, which can promote recovery in neurodegenerative conditions by overriding cell death pathways. The molecule responsible for activating death pathways in the nervous system is called p75. This project will investigate how p75 results in cell death, how synaptic signals can prevent the activation of the p75 death pathway and whether blocking p75 function can limit neurodegeneration.
Decoding The Transcriptional Program Of Vessel Growth In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Mechanisms Of Abnormal Expression Of The IGF2 Gene In Disorders Affectin Foetal Growth
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
The IGF2 gene is crucial for foetal growth. Only the copy inherited from the father is active, a phenomenon named parental imprinting. In some children with foetal overgrowth or growth retardation, the deregulation of imprinting of the IGF2 gene during the first days of foetal development will influence subsequent growth and will also have major implications in post-natal and adult life. We will investigate the mechanisms resulting in abnormal imprinting of IGF2 early in development.
Nfi Genes Regulate The Switch Between Neurogenesis And Gliogenesis During Cortical Development
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Cells within the brain fall into two categories; neurons or glia. Importantly, both derive from a common progenitor population, the radial glia, during development. Early in development radial glia produce neurons, while later they generate glia. The genes which control the switch from neuron production to glia production remain poorly defined. I propose to investigate how this switch is controlled in radial glia, focussing on a family of proteins known to regulate gene transcription.
Understanding ILC1 Transcriptional Regulation And Function In Immune Protection
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
Natural killer cells are innate cells that provide first line defense against infection and cancer. The recent discovery of a novel innate cell population has modified our vision of the early events necessary for immune protection. Understanding the role of these cells is critical as they could represent viable therapeutic targets. We have developed unique mouse models to experimentally target this population to determine how they are generated and their role in combating infection and cancer.
Fetal Cardiovascular Development And The Impact Of Chronic Hypoxia And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$307,232.00
Summary
Low birth weight occurs in 7% of Australian babies and is associated with an increased risk of cardiovascular disease in adult life. Understanding the mechanisms underlying heart and blood vessel development in low birth weight babies will lead to improved identification and intervention in those individuals at risk of cardiovascular disease in adult life, improving heart health for Australians. Reducing cardiovascular disease will improve both quality and quantity of life for Australians.