Defining The Genes That Dictate The Cellular Response To Tumour Protein TP53 Activation
Funder
National Health and Medical Research Council
Funding Amount
$784,896.00
Summary
The tumour suppressor TP53 prevents the growth of abnormal cells by activating processes such as cell death and irreversible growth arrest. A cell will undergo only one of these possible responses, but it is not known why some cells die and others only stop growing. We will use innovative methods to define the genes that dictate the cellular response to TP53 activation. This research has implications for cancer, as many therapeutics aim to permanently kill cancer cells by activating TP53.
Exploiting Messenger RNA Export As A Novel Therapeutic Strategy To Treat Cancer
Funder
National Health and Medical Research Council
Funding Amount
$948,098.00
Summary
Novel therapies for cancers represent an area of unmet clinical need. We have identified a new biological pathway implicated in cancer, namely selective mRNA export. Compounds inhibiting other steps of the gene expression pathway are promising therapeutic candidates for cancer, yet mRNA export inhibitors do not exist. We propose to develop first-in-class inhibitors of mRNA export that selectively target transcriptionally addicted cancers with dysregulated RNA processing.
Epigenetic Reprogramming Of Calcified Vascular Smooth Muscle Cells As A Treatment For Vascular Calcification
Funder
National Health and Medical Research Council
Funding Amount
$1,285,195.00
Summary
Pathological hardening of blood vessels, or vascular calcification, is a frequent and deadly complication of many cardiovascular disorders. It is caused by the irreversible change in mature vascular smooth muscle cells (the main cell type in the blood vessel walls) to a bone-forming cell type. We have now identified a new gene that can potentially revert calcified vascular cells back to their physiological state. This represents a promising new approach for treatment of vascular calcification.
Characterisation Of Erusiolin - A New Peptide Hormone
Funder
National Health and Medical Research Council
Funding Amount
$547,202.00
Summary
Obesity and type II diabetes are epidemic diseases in Australia. Gut-derived hormones are key mediators in these diseases, due to their role in regulating appetite and blood glucose levels. Therapeutic modulation of these hormones also provides significant benefits for patients. In this proposal, we will determine the metabolic functions, such as appetite control, for a previously uncharacterised hormone, which is an unexplored therapeutic target for obesity and diabetes.
The Role Of LINE Encoded Natural Antisense Transcripts In Immune Regulation
Funder
National Health and Medical Research Council
Funding Amount
$934,853.00
Summary
Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. This proposal aims to utilize cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes in human autoimmune disease.
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.
Repurposing Thalidomide Derivatives To Augment Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$1,154,196.00
Summary
Immunotherapies are a revolutionary approach for cancer treatment, but most people with cancer do not respond to therapy. We have identified a new set of molecular switches that shutdown immune function and limit responsiveness to existing immunotherapies. Importantly, we have found a class of approved drugs that can block these immune 'off switches'. This proposal will test if these drugs could be repurposed as a novel treatment to amplify the efficacy of existing immunotherapies.
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
Dendritic cells are essential components of our immune systems. They are located throughout our body and provide the first line of defence against invading microbes. Dendritic cells sense the invader and send out signals to recruit our immune cells to the site of infection. Our research aims to understand how our dendritic cell network is set up and how it functions to promote our immune health.
Feeding Behaviour And Obesity Development: Identification Of Novel Intervention Points
Funder
National Health and Medical Research Council
Funding Amount
$923,668.00
Summary
Appetite and food intake is regulated by specific neuronal structures in the brain. The most important area is the hypothalamus from which many neuronal pathways originate to control specific aspects of feeding behaviour and energy usage in the brain and the rest of the body. To better understand the contribution individual neuronal populations make to drive excess food intake we propose a new approach to identify this, making new treatment options for eating disorders and obesity possible.