Defining The Role Of RNA Editing In Erythropoiesis
Funder
National Health and Medical Research Council
Funding Amount
$628,945.00
Summary
We are seeking to understand how red blood cells are produced. We have identified that a process called RNA editing may be important in the regulating the production of red blood cells.
Reactivities Of CD8 T Cells To Mutated Neo-antigens In Lung Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
Tumours express mutated proteins (called ‘neo-antigens’) which can be targets of powerful killer T cells which can destroy cancer cells. To understand why these cells fail to cure most cancers we will study neo-antigens identified by modern DNA sequencing methods to identify these neo-antigens & the responses to them. Then it will be possible to design trials in individual patients, e.g. personalised vaccines to ‘force’ the immune system to attack cells bearing these neo-antigens.
A Comprehensive Analysis Of The Role Of The Alcohol Dehydrogenase Gene Cluster In Alcohol-related Disorders And Esophageal Cancer Through Deep Resequencing
Funder
National Health and Medical Research Council
Funding Amount
$605,323.00
Summary
Excessive alcohol consumption remains a major public health concern in Australia where the burden of mental health disorders is dominated by substance-use disorders. Alcohol dehydrogenases (ADHs) are essential in the breakdown of alcohol in the body and we seek to resequence seven ADH genes with the aim to comprehensively catalogue and identify sequence variants that contribute to risk for consuming excessive quantities of alcohol, alcoholism and esophageal squamous cell carcinoma.
Identifying Glaucoma Risk Variants In The Norfolk Island Genetic Isolate
Funder
National Health and Medical Research Council
Funding Amount
$658,447.00
Summary
Primary open angle glaucoma is the most common form of glaucoma. In this project we will focus on the identification of functional genetic variants influencing development of this disorder, using a powerful whole exome sequencing approach in a large multigenerational pedigree from the Norfolk Island population isolate. The identification of genes influencing glaucoma development would provide invaluable clues to aid in defining the pathophysiology of this common disease.
Interrogation Of Streptococcal Genomic Epidemiology Within Disease Endemic Regions
Funder
National Health and Medical Research Council
Funding Amount
$325,896.00
Summary
Group A streptococcal (GAS) bacterial infections within the Indigenous populations of Northern Australia are amongst the highest in the world. This project uses comparative bacterial genomics to examine current and historical outbreaks of GAS disease in Northern Australia relative to globally sourced GAS. This will be used to examine the spread of disease causing GAS between remote communities as well as investigating genetic markers of disease and informing therapeutic interventions.
Identification Of Microbiome Control Of Weight Loss During Dietary Intervention In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$644,667.00
Summary
We will develop diagnostic tests that enable prediction of the optimal weight loss diet for patients. Obesity is a growing problem in Australia and weight loss is of proven health benefit. Dieting is capable of delivering useful weight loss but long term success rates are poor. The variable success rates are linked to differences in gut microbiota. Diagnostic tests based on the gut microbiota in stool samples will allow identification of the optimal weight loss diet for individuals.
Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.
How Are Klebsiella Pneumoniae Infections Acquired In Hospital?
Funder
National Health and Medical Research Council
Funding Amount
$496,228.00
Summary
Klebsiella pneumoniae (Kp) bacteria are among the top causes of hospital infections and are often resistant to a wide range of antibiotics. While some hospital bugs are well-studied, we are considerably behind in our understanding of Kp, which can be carried in our bodies as a commensal without causing disease. Bacterial genomics will be used to dissect how Kp infections are acquired in hospital, including investigating the evidence for hospital transmission and the role of commensal carriage in ....Klebsiella pneumoniae (Kp) bacteria are among the top causes of hospital infections and are often resistant to a wide range of antibiotics. While some hospital bugs are well-studied, we are considerably behind in our understanding of Kp, which can be carried in our bodies as a commensal without causing disease. Bacterial genomics will be used to dissect how Kp infections are acquired in hospital, including investigating the evidence for hospital transmission and the role of commensal carriage in causing serious hospital infections.Read moreRead less
Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
Understanding Age-related Protein Aggregation. The Mechanism Of Cataract And Its Prevention
Funder
National Health and Medical Research Council
Funding Amount
$709,333.00
Summary
Cataract arises from clouding of the eye lens due to the aggregation of crystallin proteins whose high concentration and close packing facilitate lens transparency. This proposal will investigate crystallin structure and interactions to understand the reasons for cataract formation and its prevention via the design of aggregation inhibitors. The results will facilitate the development of drugs to prevent cataract and other related protein aggregation diseases, e.g. Alzheimer’s and Parkinson’s.