High-throughput genetic assays are commonly used to study the molecular basis of disease and such technology requires sophisticated data analysis methods that account for significant biological and experimental complexity. Specialized methods will be developed in free public software that will greatly benefit future genetic profiling studies.
A Comprehensive Genomic Analysis Of Oesophageal Adenocarcinoma: Understanding The Genetic Aetiology Of OAC Towards Biomarkers Of Progression, Prognosis And Targeted Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$987,906.00
Summary
Oesophageal cancer (OAC) continues to have poor survival despite surgery, chemotherapy and radiotherapy. Selecting patients for the most appropriate therapies and improving survival remain unmet research needs. We propose to undertake a detailed genetic study of OAC, including “next generation” sequencing, in order to catalogue the genetic changes in the disease. This information forms an essential basis for identifying genetic signatures of OAC progression, prognosis and treatment response.
Computational And Statistical Methods For The Analysis Of RNA-Seq Data
Funder
National Health and Medical Research Council
Funding Amount
$406,545.00
Summary
New sequencing technologies provide medical researchers with ultra high-resolution tools for measuring gene activity in healthy and diseased cells. These instruments generate unprecedented volumes of data that requires careful analysis to maximize the biological insight learned from each experiment. Our research will develop new tools for analyzing, interpreting and making medical discoveries from this rapidly emerging technology, for the benefit of Australian biomedical researchers.
Selective Modulation Of Neural Network Activity Using Focal Brain Stimulation
Funder
National Health and Medical Research Council
Funding Amount
$531,496.00
Summary
Transcranial magnetic stimulation (TMS) has been touted as a viable treatment for a range of psychiatric and neurological disorders. However, the extent to which localised TMS influences widespread brain networks remains unknown. To fill this gap, we will combine neuroimaging and TMS in healthy adults. The project will provide a scientific foundation for the use of brain stimulation as an effective tool for improving function in a range of clinical conditions.
Epigenetic Predictors Of Outcome In Malignant Glioma
Funder
National Health and Medical Research Council
Funding Amount
$697,720.00
Summary
Human high grade gliomas (HGG) present as heterogeneous disease, primarily defined by the histologic appearance of the tumor cells.Glioblastoma multiforme (GBM) is the most common illness and continues to have a very poor prognosis, despite the use of multimodality therapy including surgery, radiation therapy and chemotherapy. We will use our existing biobank of specimens, clinical information and molecular investigation to identify factors that determine outcomes.
Patients with schizophrenia differ widely in their symptoms, long-term outcome and response to medication. However, most patients are treated with the same medications and interventions. This study aims to better facilitate the targeting of novel treatments to groups of patients (biotypes) that are likely to benefit most from a treatment. Groups of patients that share distinct patterns of deficits in brain connectivity will be delineated using state-of-the-art white matter imaging techniques.
Epigenetic Therapies To Differentiate And Eradicate Leukaemia Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$674,315.00
Summary
Leukemia stem cells (LSC) are often resistant to conventional and targeted therapies and therefore serve as the seed for leukaemia relapse. The overall aim of this project is to use small molecule therapies to block the activity of a particular protein (LSD1) in LSC in order to differentiate them and expose a vulnerability to another epigenetic therapy called a BET inhibitor. Together, these epigenetic therapies will differentiate and eradicate LSC, leading to improved outcome in AML.
Chromosomal translocations in the MLL gene results in aggressive leukaemias. Several drugs developed to target proteins that interact with the MLL fusion proteins are now being tested in the clinic. Despite this progress, our understanding of how the MLL fusion proteins cause leukaemia remains incomplete. In particular, it is unclear how the MLL fusion protein drives the development of leukaemia. In this project I will address these important issues with cell and molecular biology methods.
Systems Biology Of Asthma Development In Early Childhood
Funder
National Health and Medical Research Council
Funding Amount
$763,800.00
Summary
Recent studies have established that both human genetic susceptibility and viral infections during early childhood are important drivers of asthma development. It has also been noted that asthmatics’ airways are colonized with different bacteria to non-asthmatics. In this project we will examine how genetic susceptibility and interactions between bacteria and viruses in children's airways promote the development of allergy and asthma.
Robust Bioinformatics For Predicting Bacterial Pathogens From Microbiome Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$644,151.00
Summary
We propose to develop new methods for the identification of microbial pathogens using High Throughput DNA Sequencing (HTS). Study of the microbiome - the genes encoded by the assemblage of microbial species present in an environment - using HTS technologies is revolutionising our understanding of human-microbe interactions. Our proposed work includes fundamental computational and theoretical advances and applying these techniques to solve critical problems in pathogen detection.