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.
Development Of Statistical Methodologies And Application To Clinical Cancer Studies
Funder
National Health and Medical Research Council
Funding Amount
$428,065.00
Summary
Integrating different layers of information coming from the recent ‘-omics’ technologies can help improving the treatment and the prevention of complex diseases. In particular, the identification of molecular markers of different types can be used for better diagnostics and prognosis in cancer and immune diseases. This project will develop innovative statistical solutions to handle and make sense of the vast amount of biological data that are routinely generated in the laboratories.
Detection Of Cardiac Allograft Rejection By Peripheral Blood Gene Expression: A Novel Concept Of Personalized Approach To Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$292,705.00
Summary
Heart biopsy is required to detect rejection after heart transplantation. The cost of each biopsy is around $7,000 and at least 10 heart biopsies needed in the first post-transplant year alone. The biopsy is difficult for the patients and significant cost for the Australian healthcare system. Thus, it would be beneficial to identify rejection using a simple blood test. Such tool would help to reduce or eliminate the need for expensive heart biopsy and would reduce the cost by about 10 times.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Molecular Characterisation And Diagnosis Of Malignant Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$421,250.00
Summary
Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in ....Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in cases of mesothelioma is not expected until 2010. MM is one of the most aggressive and debilitating tumours known, with a median survival of 7-10 months and a clinical pattern that usually involves substantial pain and dyspnea. Advances in therapy-prevention of mesothelioma will have not only have a major health impact, but potentially an extraordinary economic impact. MM is predicted to cost the Australian economy around $5 billion in compensation over the next 35-40 years. Government, insurance companies and industry will share that cost. The significance of this disease therefore extends beyond its actual incidence. There is growing evidence in many tumour types that the best diagnostics and treatments for cancer will come about as a result of understanding the molecular logic that underpins carcinogenesis, and designing therapies and diagnostics accordingly. We will carry out a project using the most comprehensive microarrays available to profile gene expression in malignant mesothelioma. We will use the expression data we obtain to fulfil three aims. Firstly, we will use patient outcome information to search for genes whose expression is indicative of response to therapy. Secondly, we will search the data to identify candidate secreted molecules which may be useful in the early detection of MM. Finally, we will develop a molecular assay to unequivocally diagnose MM from cells collected from pleural effusions.Read moreRead less
Extending Life After Lung Transplantation – Defining The Structural And Immunological Drivers Of Chronic Lung Allograft Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$739,190.00
Summary
Lung Transplantation (LTx) saves life. However, chronic rejection limits survival after LTx compared to other solid organ transplants. Chronic rejection develops when the LTx recipient produces antibodies against the donor lung. With a team of global leaders in the field we will dissect the antibody response to LTx. By better understanding the immune drivers of antibody-mediated rejection, we aim to reduce the incidence of chronic rejection thereby improving survival after LTx.
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.
Investigation Into Host Susceptibility And Immune Responses In Young Children With Acute Wheezing Due To Human Rhinovirus Group C Infection
Funder
National Health and Medical Research Council
Funding Amount
$682,711.00
Summary
We recently made the surprising discovery that a new viral group, human rhinovirus group C (HRV-C), causes the majority of acute asthma in children. We also found that it causes half of the acute wheezing attacks in younger children, and is the only respiratory virus associated with allergy. So, HRV-C may be the key to the relationship between allergy and asthma. The planned project will focus on whether young children who wheeze with HRV-C have related defects in their immune system.
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
Cyclin E1 As A Therapeutic Target In Women With High-grade Serous Cancer And Primary Treatment Failure
Funder
National Health and Medical Research Council
Funding Amount
$644,170.00
Summary
Ovarian cancer is the 5th most common cancer in women and the most lethal gynaecologic malignancy. We found tumours with extra copies of the CyclinE1 gene (CCNE1) are less likely to respond to standard treatment, and show reliance on its activity. Therefore, targeting CCNE1 may be a novel treatment strategy for these cancers. We will perform preclinical studies with therapeutic inhibitors towards the CCNE1 pathway and further explore the underlying biology of tumours with CCNE1 amplification.