Novel Transcription Factor Regulation Of Lymphatic Vascular Angiogenesis In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$831,568.00
Summary
Lymphatic vessels control tissue fluid drainage, inflammatory processes and cancer progression. We have used genetic approaches to discover an unexpected role for a family of factors (transcription factors) that regulate new lymphatic vessel formation. This project will investigate this biological function of these genes in detail in vascular formation. The project aims to generate important knowledge for vascular biology, vascular pathologies, cancer spread and future therapeutics.
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.
Functional And Molecular Characterization Of A Novel Regulator Of Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$474,907.00
Summary
All cells in the body require blood vessels for the provision of nutrients and waste-removal. A deficiency of vessels prevents proper healing whereas an overabundance is a hallmark of diseases such as cancer and macular degeneration. This research will investigate a novel gene that is essential for new vessel growth. The project aims to understand the mechanism of how this gene functions. Ultimately, the research aims to inform therapeutic development for stimulating or inhibiting vessel growth.
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
Models Of Cerebellar Function During Motor Learning
Funder
National Health and Medical Research Council
Funding Amount
$384,775.00
Summary
The cerebellum is responsible for smooth movements and for learning new patterns of motions, but many details of how it works are unclear. We aim to describe neural activity in the cerebellum while motor learning is in progress, and determine exactly what patterns of activity lead to the acquisition of new types of learned movement. The basic knowledge gained will contribute to a better understanding of cerebellar disorders including nystagmus, ataxia, and loss of motor control with ageing.
Bacterial And Host Drivers Of Fulminant Community-acquired Acinetobacter Baumannii Infection
Funder
National Health and Medical Research Council
Funding Amount
$729,315.00
Summary
This proposal aims to understand how a bacterial pathogen causes severe, life-threatening infections in people from the community in northern Australia. This severe infection particularly impacts people who drink excess alcohol or have diabetes mellitus, and importantly impacts Indigenous Australians the greatest. This work will provide, for the first time, important insights into new prevention and treatment strategies for a serious infection impacting Australians and those in our region.
Nocturnin: A Post-transcriptional Regulator Of Circadian Fat Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$574,696.00
Summary
Our metabolism is aligned with the 24-hour rotation of the earth in what is termed the circadian clock. Being misaligned to this clock explains jetlag and the poor health associated with shift-workers. For example, whether fat is utilised or stored depends on the time of day. This study aims to investigate the post-transcriptional mechanisms that underpin the rhythmic changes that occur throughout our bodies to ensure that our metabolism is matched to our environment.
Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Many human muscle diseases are caused by mutations in genes encoding skeletal muscle actin. Actin is a major building block of the sarcomere, the engine of muscle contraction. Our studies have identified a mutation in chaperonin, the main protein-folding complex responsible for actin folding, which results in a muscle defect. These results have led to a novel hypothesesis, which we test in this grant, namely that as the chaperonin complex can act as a modulator of of muscle disease.
The Role Of Myo18b In Myopathies And Sarcomere Assembly
Funder
National Health and Medical Research Council
Funding Amount
$860,776.00
Summary
Muscle force is provided by a specific structure within the muscle cell termed the sarcomere. Sarcomeres are the engine-room of muscle cells, that act as complex cellular machines to controls muscle contraction. Many muscle degenerative disorders are caused by defects within the sarcomeres, but how this occurs is not well understood. This grant examines how one such muscle waiting disease, or myopathy, results from mutations in a gene encoding a component of the sarcomere called Myo18b.