Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Clinical Application Of Genomic Approaches For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$707,370.00
Summary
Cancer is the cause of 1 in 8 deaths worldwide. Cancer occurs due to errors or mutations in the DNA of normal cells. I will identify the mutations in tumour cells, which will tell us: i) How the tumour started and grew ii) How to treat the tumour and kill the cancer The work involves a variety of cancer types including mesothelioma, melanoma, oesophageal and breast cancer. The overall aim is to apply some of the research findings or approaches into patient care to improve patient survival.
Drinking from the fire hose - Making sense of high density genetic and genomic data. The project will improve our understanding of the genetic component of common complex diseases such as cancer. Identification of genetic variants underlying disease risk is currently one of the primary means for increasing our understanding of the biochemical and developmental pathways involved. Genetic studies rely on sophisticated statistical and computational (bioinformatics) techniques. This project centres ....Drinking from the fire hose - Making sense of high density genetic and genomic data. The project will improve our understanding of the genetic component of common complex diseases such as cancer. Identification of genetic variants underlying disease risk is currently one of the primary means for increasing our understanding of the biochemical and developmental pathways involved. Genetic studies rely on sophisticated statistical and computational (bioinformatics) techniques. This project centres on the development, refinement and application of novel statistical analysis methods in genetics. Future advances in statistical and computational methods are essential if we are to exploit the large volumes of genome data now being generated to help develop diagnostics and interventions to improve public health.Read moreRead less
Translation Of PALB2 Genetic Information Into Breast Cancer Clinical Genetic Services
Funder
National Health and Medical Research Council
Funding Amount
$423,081.00
Summary
Today in Australia women attending clinical genetics services and receiving genetic counselling due to a personal and/or family history of breast cancer are not considered for testing of PALB2 despite mounting evidence that the risk of breast cancer in mutation carriers is at least as high as the risk for BRCA2 mutation carriers. This project will provide the evidence base to support the incorporation of PALB2 gene testing into routine clinical genetics services both in Australia and around the ....Today in Australia women attending clinical genetics services and receiving genetic counselling due to a personal and/or family history of breast cancer are not considered for testing of PALB2 despite mounting evidence that the risk of breast cancer in mutation carriers is at least as high as the risk for BRCA2 mutation carriers. This project will provide the evidence base to support the incorporation of PALB2 gene testing into routine clinical genetics services both in Australia and around the world.Read moreRead less
Skeletome - A Curated Online Knowledge Base Integrating Clinical and Biological Information on Skeletal Dysplasias and Related Conditions. The skeletal dysplasia knowledge base will:
* establish Australia as a world-leader in skeletal dysplasia research;
* provide researchers with an extensible and comprehensive online knowledge-base related to skeletal dysplasias;
* enhance clinicians' understanding of the diagnosis, treatment and management of skeletal dysplasias;
* facilitate collaborativ ....Skeletome - A Curated Online Knowledge Base Integrating Clinical and Biological Information on Skeletal Dysplasias and Related Conditions. The skeletal dysplasia knowledge base will:
* establish Australia as a world-leader in skeletal dysplasia research;
* provide researchers with an extensible and comprehensive online knowledge-base related to skeletal dysplasias;
* enhance clinicians' understanding of the diagnosis, treatment and management of skeletal dysplasias;
* facilitate collaborative discussions by patients, clinicians and researchers around specific cases to improve training, management and diagnosis; and
* enhance Australia's research expertise in Semantic Web and social networking technologies.Read moreRead less
Epigenetic Hyperglycemic Cell Memory Causes Vascular Complications In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$332,140.00
Summary
This project seeks to identify how epigenetic change in response to hyperglycemia can cause vascular complications of diabetes, and how this contributes to “hyperglycemic memory”; a phenomena where cells may undergo gene modifications which increase risk to further complications later in a patients life. These studies are the first of their kind and will characterize the types of epigenetic change that can cause human disease.
Identification And Characterisation Of A Novel Genetic Signature At The 5p15 Region Associated With Risk Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$610,974.00
Summary
We have recently replicated the genetic association of a region (5p15) with the risk of prostate cancer in Australian men. We now seek to identify the precise genetic variant behind this association, and the functional role of these novel gene/s and variants in disease pathology. Our results will provide a foundation for the development of sensitive and readily applicable lab-based screening tools to be used clinically and will also provide impetus for drug-targeted research by furthering our un ....We have recently replicated the genetic association of a region (5p15) with the risk of prostate cancer in Australian men. We now seek to identify the precise genetic variant behind this association, and the functional role of these novel gene/s and variants in disease pathology. Our results will provide a foundation for the development of sensitive and readily applicable lab-based screening tools to be used clinically and will also provide impetus for drug-targeted research by furthering our understanding on this multifactorial disease.Read moreRead less
Evolutionary Genomics Approaches For Studying Acquisition Of Drug Resistance In Tumours
Funder
National Health and Medical Research Council
Funding Amount
$313,390.00
Summary
Chemotherapy often fails because some of the cells in tumour evolve resistance to the drugs the patient is given, causing relapse. We study how a tumour’s unstable genome and high rate of mutation drives its evolution by observing tumour cells in the laboratory as they evolve resistance to drugs and the genetic differences between resistant and sensitive cells. This work will help develop therapeutic strategies to prevent tumours from evolving resistance to chemotherapy.