A New Class Of Inhibitors For The Treatment Of Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$720,691.00
Summary
Tuberculosis (TB) remains a major cause of mortality and morbidity worldwide, with 1.3 million deaths annually. Some strains of the TB bacterium are resistant to all available drugs. We have identified novel chemical structures that display potent and specific activity against pathogenic mycobacteria. In this proposal we will develop optimised derivatives with more potent activity against mycobacteria, assess their stability and toxicity and determine their mode of action.
Prevention And Treatment Of Bone Infection With CSA-90
Funder
National Health and Medical Research Council
Funding Amount
$350,983.00
Summary
Bone infections are a major challenge to treat, especially with the rise of drug resistant “superbugs”. We have access to a new agent, CSA-90, that has dual properties of being anti-microbial (antibiotic) and helps encourage bone growth. This project aims to expand upon our prior research and test CSA-90 for the treatment of chronic bone infections. We will also look at applying this technology to joint replacements and this drug may be particularly useful for coating orthopaedic implants.
Targeting A Master Regulator Of Tumour Cell Plasticity As A New Adjuvant Therapy For Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$780,338.00
Summary
Prostate cancer (PCa) claims the lives of over 3,000 Australian men each year. This highlights the urgent need to identify new molecular targets that can be developed as additional therapies for men with PCa. Our team has identified the protein, Zeb1, to be highly expressed in aggressive and treatment resistant forms of PCa. This study aims to characterise the role of Zeb1 in the lethal progression of PCa and to develop a new therapeutic agent to inhibit the production of ZEB1 by cancer cells.
Deep Brain Stimulation In The Treatment Of Severe Depression
Funder
National Health and Medical Research Council
Funding Amount
$1,008,087.00
Summary
Some patients with depression fail to respond to a variety of standard treatments and in this group, deep brain stimulation (DBS) is being evaluated as an alternative treatment option. This study will investigate the use of DBS applied to a novel brain target site in patients with highly treatment refractory depression.
Early Intervention For Treatment-resistant Conduct Disorder In Children
Funder
National Health and Medical Research Council
Funding Amount
$694,280.00
Summary
Conduct problems (CP) in childhood are the most reliable precursor of all types of adult mental health problems. Conclusive evidence now exists to show that a subgroup within CP children, those with high levels of callous-unemotional (CU) traits are etiologically distinct and are relatively unresponsive to existing evidence-based treatments.The aim of the current programme is to test a new treatment for these children.
Deciphering Tumour Heterogeneity Of Breast Cancer Metastases Using Barcoded Patient Derived Xenografts
Funder
National Health and Medical Research Council
Funding Amount
$583,161.00
Summary
Breast cancer mortality is largely due to metastases that seed from the primary tumour. Breast tumours are known to contain a heterogeneous mix of cells, but the precise way that cells are selected for tumour growth and metastasis (as well as their response to systemic therapy) is not well understood. In this study we will use patient samples and cellular ‘barcoding’ to track the destiny of every single clone throughout disease progression and study the effect of various therapies on metastasis.
Mechanisms Of Stable Gene Inheritance In Multiresistant Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$620,357.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections in Australia and around the world. The bacteria have mechanisms that cause efficient inheritance of resistance genes, even when antibiotics are no longer being used. This project will elucidate key aspects of such mechanisms so that treatments can be devised that interfere with the development and maintenance of resistance.
Horizontal And Vertical Transmission Mechanisms Of Staphylococcus Aureus Multiresistance Plasmids
Funder
National Health and Medical Research Council
Funding Amount
$408,993.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections. The bacteria have mechanisms that cause efficient transmission of resistance genes to their offspring as well as to other strains. This project aims to elucidate key features of these mechanisms so that treatments can be devised that disrupt the maintenance and transfer of resistance, so as to prolong the effectiveness of antibiotics.
Redefining Antibiotic Resistance Plasmid Transfer In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$735,585.00
Summary
Multidrug-resistant Golden Staph bacteria are a major health problem. Resistance develops rapidly because bacteria efficiently acquire/share resistance genes. Our discoveries suggest DNA transfer mechanisms are far more diverse and widespread than previously expected and this has wide-reaching implications for numerous pathogenic organisms. This project aims to define the prevalence and key features of each mechanism so treatments can be devised to disrupt the evolution and spread of resistance.
N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$981,789.00
Summary
Many patients with schizophrenia remain treatment resistant even after “last resort” medications like clozapine. This proposal will conduct a novel multi-site randomised placebo controlled trial of adjunctive N-acetyl cysteine in patients with clozapine resistant schizophrenia. Treatment efficacy will be examined at 8, 26 and 52 weeks.