Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statis ....Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statistical methods provide the opportunity to close this gap. The outcome will be identification of many genomic variants causing variation in complex traits. This will benefit scientific understanding of complex traits and the ability to predict traits for individuals from their genome sequence.Read moreRead less
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
Defining The Molecular Effectors Of Gene/environment Interaction On Mouse Heart Development
Funder
National Health and Medical Research Council
Funding Amount
$749,271.00
Summary
One third of all birth defects involve the heart, and are the most common cause of infant death. Some defects are due to genetic factors, but others arise when the pregnant mother is exposed to environmental stress. We will examine how one stress (low oxygen levels) causes abnormal heart formation in the embryo, look at what causes this at a molecular level, and explore if such stress increases the risk of heart defects in families with a history of such abnormalities
This study aims to elucidate central pathways which can be manipulated to drive the storage of excess energy away from fat and instead directing it into the production of bone mass. Having identified leptin-responsive NPY neurons as important in the control of energy partitioning, we will focus on manipulating these neurons in the hypothalamus using innovative technology to alter body composition. This research has the potential to result in novel treatments for obesity and osteoporosis.
Single-cell Optical Window Imaging In CDK1-FRET Biosensor Mice To Assess Tissue Stiffness And Optimise Delivery And Therapeutic Response To Gemcitabine/Abraxane In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Inefficient drug response in solid tumour tissue is commonly a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug targeting in order to improve the encouraging anti-cancer profile of the new drug combination Gemcitabine/Abraxane in pancreatic cancer.
Biosensor Imaging In Preclinical Pancreatic Cancer Targeting: Taking Cancer Targeting To New Dimensions.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Using cutting-edge imaging technology and 3D models that mimic cancer, we can map areas of poor drug response within distinct 'stages' or regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug response in order to improve the encouraging anti-cancer profile of new or current drugs in pancreatic cancer.
Therapeutic Targeting Of Cell Cycle Checkpoint Aberrations In Pancreatic Cancer: Personalised Medicine In Action
Funder
National Health and Medical Research Council
Funding Amount
$634,354.00
Summary
Less than 5% of people with pancreatic cancer (PC) survive 5 years, and the odds of patients beating this disease have remained unchanged for 50 years. Consequently, there is an urgent need to develop novel treatment approaches for this highly aggressive cancer. Our study aims to define novel therapeutic strategies for PC utilising specific anti-proliferative therapies and a personalised “companion biomarker” directed strategy.
Methods to infer dense genomic information from sparsely genotyped populations. Prediction of phenotype based on DNA polymorphisms or sequence has important applications such as prediction of disease risk in human medicine and prediction of genetic value in plant or animal breeding. This project will enhance precision and lower the cost of association studies leading to substantial increase in accuracy of such predictions. This will allow more effective genetic improvement, particularly of diff ....Methods to infer dense genomic information from sparsely genotyped populations. Prediction of phenotype based on DNA polymorphisms or sequence has important applications such as prediction of disease risk in human medicine and prediction of genetic value in plant or animal breeding. This project will enhance precision and lower the cost of association studies leading to substantial increase in accuracy of such predictions. This will allow more effective genetic improvement, particularly of difficult but important traits such as disease resistance, reduced green-house gas emissions and product quality. The same methods can be extended to improve genetic improvement in plants and better prediction of human disease risk. Read moreRead less
Solving Delivery Of Gene Therapy For Control Of Human Immunodeficiency Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$765,439.00
Summary
Antiretroviral therapy free control of Human Immunodeficiency Virus (HIV) infection requires control of the viral reservoir. We have a unique approach, aimed at enforcing HIV latency by targeting highly conserved regions in the viral promoter. These constructs completely silence viral transcription for long periods of time. We intend to develop & assess vectors that are specifically targeted to the reservoir and which can enforce viral latency despite immune activation or viral variation.