Investigating The Pathogenic Mechanisms Of Mutations In The ARX Homeobox Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$596,222.00
Summary
Intellectual disability is frequent in the population with as many as 1 in every 50 people in the world directly affected. The cost to Australia of intellectual disability is estimated at $14 billion annually. ARX is one of the most frequent genes mutated in X chromosome linked intellectual disability. Our study will specifically address the functional impact of these mutations using cell models relevant to the brain to better understand the pathways and networks required for normal cognition.
The Essential Nuclear Transporter Importin 13; Key Role In Brain And Testis
Funder
National Health and Medical Research Council
Funding Amount
$613,124.00
Summary
Transport into and out of the nucleus, the control centre of cells, is critical for cell function in complex organisms such as mammals. The present proposal seeks to further understanding of a novel molecule mediating nuclear transport that has a novel inhibitory form in the testis, and important roles in the lung and nervous system. The results should help basic understanding of this molecule, and relate to disease conditions such as X-linked mental retardation and childhood asthma.
Differential Changes In Cortical Tumour Necrosis Factor Signalling In Mood Disorders And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$642,078.00
Summary
Changes in inflammation-related pathways contribute to the symptoms of psychiatric disorders and tumour necrosis factor ? (TNF) is a protein central to regulating theses pathways. We have now shown that changes in pathways regulated by TNF are present in the brains of people with schizophrenia and mood disorders. This means that the symptoms experienced by those with the different disorders may be linked to differential changes in TNF-regulated pathways in the brain.
Acetohydroxyacid Synthase: A New Drug Target For Human Fungal Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$536,914.00
Summary
The aim is to discover new compounds that have the ability to reduce the growth of invasive human fungal pathogens including Candida albicans, Cryptococcus neoformans and Aspergillus nidulans. These infectious agents are highly prevalent in hospital patients that are immuno-compromised. The compounds have a common feature in that they prevent the synthesis of valine, leucine and isoleucine which are key metabolites required for the survival of these fungi in the human host.
Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
Understanding The Role Of The Scaffolding Protein D13 In Poxvirus Assembly And Its Inhibition By Rifampicin
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
Smallpox is one the most notorious diseases in human history. Despite its eradication in the 1970s, human cases of animal poxviruses such as monkeypox virus and the potential use of smallpox as a bioterrorism weapon have called for an improved preparedness of Australia against (re)-emerging poxviruses. This project combines structural biology approaches to understand the complex assembly of poxviruses and provide the basis for the development of broad-spectrum antiviral drugs.
Coupling The Cell Cortex To Membranes: Structural Basis For The Activation And Control Of Ezrin
Funder
National Health and Medical Research Council
Funding Amount
$587,548.00
Summary
Cells are dynamic: they change shape, communicate with each other and import/export signalling molecules. These dynamic processes are controlled via the interaction of the cell membrane with the underlying actin cytoskeleton and they are important for health, for example, they are critical for proper immune cell function. The goal of this project in to unravel the control of membrane dynamics by defining the interactions between the cell membrane and the proteins: ezrin and RhoA.
Epigenetic Regulation Of Monoallelic Gene Expression During Development.
Funder
National Health and Medical Research Council
Funding Amount
$655,035.00
Summary
Upon completion of the human genome sequence focus has shifted to understanding the epigenetic mechanisms that help interpret the encoded information to allow the cell growth and differentiation essential for an organism during development. These mechanisms are disrupted in diseases like cancer, where gene expression is disrupted to favour disease progression. This project will study the genes and epigenetic mechanisms that determine how gene expression patterns are established and maintained.
Novel Insights Into The Molecular Mechanisms Of Manganese Recognition And Acquisition By Pathogenic Bacteria.
Funder
National Health and Medical Research Council
Funding Amount
$843,035.00
Summary
Streptococcus pneumoniae is the world’s foremost bacterial pathogen. In Australia, bacterial infections are responsible for more than 9000 deaths every year, and the economic burden associated with treating diseases arising from pneumococcal infections is more than $4 billion annually. This proposal aims to define the molecular basis of how bacteria scavenge manganese from the host environment. This knowledge will provide the foundation for next generation antimicrobial therapeutics.
Novel Fragile X Syndrome Prevalence Estimates In 100,000 Australian Newborns, Prognostic And Health-economic Outcomes: A Retrospective Newborn Screening Study
Funder
National Health and Medical Research Council
Funding Amount
$769,866.00
Summary
Fragile X syndrome (FXS) is a common heritable cause of intellectual disability and co-morbid autism, caused by epigenetic silencing of the FMR1 gene. This will be the world’s largest FXS mutation prevalence study conducted in 100,000 newborns using a novel test targeting epigenetic changes, and will also explore the prognostic outcomes, costs and benefits associated with FXS newborn screening, providing conclusions regarding expanding the current newborn screening in Australia to include FXS.