We propose an integrated program of bioinformatics research and capacity building focused on functional genomics. We will address research problems in the analysis and interpretation of high-volume genomic and proteomic data, in comparative sequence analysis, in determining the relation between genotype and phenotype using mutagenesis screens, and in making effective use of single nucleotide polymorphisms. Our capacity building will focus on the research training of students (undergraduates thro ....We propose an integrated program of bioinformatics research and capacity building focused on functional genomics. We will address research problems in the analysis and interpretation of high-volume genomic and proteomic data, in comparative sequence analysis, in determining the relation between genotype and phenotype using mutagenesis screens, and in making effective use of single nucleotide polymorphisms. Our capacity building will focus on the research training of students (undergraduates through the UROP scheme, honours and PhD) and postdoctoral scholars.Read moreRead less
In the past few years, an expanding number of small RNAs (ribonucleic acids) have been discovered that play a critical part in regulating multiple steps involved in the development of human tumors. One of the genes critically implicated in the development several human cancers (including breast, lung, brain, prostate and colon) is the epidermal growth factor receptor (EGFR). As a consequence, the EGFR is a key target for new biological therapies designed to reduce signaling through the EGFR path ....In the past few years, an expanding number of small RNAs (ribonucleic acids) have been discovered that play a critical part in regulating multiple steps involved in the development of human tumors. One of the genes critically implicated in the development several human cancers (including breast, lung, brain, prostate and colon) is the epidermal growth factor receptor (EGFR). As a consequence, the EGFR is a key target for new biological therapies designed to reduce signaling through the EGFR pathway resulting in reduced growth. Using a computer-based algorithm, we have recently discovered that one of these small RNAs (or microRNAs) is a master regulator of EGFR levels in human breast and lung cancer. When we add the specific microRNA to cancer cells with excess EGFRs and low levels of microRNA, we can abolish EGFR expression almost completely, associated with cell death. From our studies, it appears that the level of this microRNA in tissues relates inversely to the level of EGFR. As the major site of expression of this microRNA is in the brain, we were intrigued to demonstrate that the normally high level of the microRNA is lost in brain cancers (or gliomas) which are associated with high levels of EGFR. Thus, the loss of microRNA may enable the tumor to develop, suggesting that the microRNA may act as a tumor-suppressor . In this project, we will investigate the functional role of this microRNA in a range of human tumors, determine if it can work synergistically with other new biological therapies targeting the EGFR signaling pathway, identify some of its binding partners and determine the levels of EGFR and the microRNA prospectively in a cohort of gliomas. These studies will determine the functional role of the microRNA and form the foundation for further studies to consider strategies to deliver the microRNA for therapeutics.Read moreRead less
Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge t ....Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge technology (DNA Chips, or microarrays) to attempt to understand why some patients suffer significant RT side-effects, while the vast majority do not. We have developed a tissue bank of samples from cancer patients who have had adverse RT reactions, and these samples (and samples from unaffected cancer patients) will be examined by microarrays: the activity of thousands of genes will be evaluated in each experiment, and we shall search for patterns of gene activity which track with RT sensitivity. Should we determine a pattern, this pattern will be checked against a larger number of cases and if it accurately predicts RT sensitivity, could lead to the routine testing of cancer patients prior to RT and the individualisation of cancer therapy. In parallel, we will evaluate the tissues of sensitive patients with assays capable of detecting abnormalities in the response to radiation, which may give clues as to an underlying gene fault(s) which might predispose to radiosensitivity in that individual.Read moreRead less
Investigating A Novel Genetic Regulator Of Cardiac Rhythm
Funder
National Health and Medical Research Council
Funding Amount
$557,101.00
Summary
Cardiac arrhythmias affect approximately 5% of the population and have a high association with sudden death. Whilst the cause of cardiac arrhythmia is complex, we know that genetic mutations play a role however we don't know all the genes important for cardiac rhythm. It is imperative that we identify all the genes in this process, so we can determine which mutations cause arrhythmia. We have identified a new gene that causes cardiac arrhythmia and seek to understand how it functions.
Systemic lupus erythematosus (SLE) is a condition which causes inflammation in many different organs and can lead to significant suffering and death. Glucocorticoids (GC) are very good at controlling inflammation, however they have severe side effects such as diabetes and bone thinning, and cannot be used long term. This project aims to investigate a protein “GILZ” in patients with SLE. GILZ may have similar anti-inflammatory effects to GC but may not be associated with the same side effects.
Human brain, pancreatic and head and neck cancers all have a poor prognosis. A gene critically implicated in these cancers is the epidermal growth factor receptor (EGFR), a key target for new therapies. We have identified a microRNA as a key regulator of the EGFR pathway in these tumors. In this project, we will investigate the functional role of this microRNA in these tumors, and determine if it can work synergistically with other new therapies targeting the EGFR pathway to improve outcomes.
Waxing And Waning Of Asthma During Transition From The Teens To Adulthood: Identification Of Immunophenotypic Markers To Predict Disease Trajectory And Guide Development Of Treatment Strategies To Prevent Progression To Chronicity
Funder
National Health and Medical Research Council
Funding Amount
$736,166.00
Summary
The project will seek to identify biomarkers in teenage/young adult asthmatics that can distinguish between those who are "growing out" of the disease, versus those who are progressing towards chronic severe asthma. This knowledge will inform the development of more effective treatment programs for this age group.