Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysica ....Developing new tools for chemical biology. We will develop new synthetic strategies to support the development of small molecule chemical probes that bind with high affinity and specificity to a target protein. Such chemical probes are invaluable in elucidating the role of specific proteins in biological pathways. Our novel strategy aims to be rapid, efficient in its use of materials and widely applicable to a range of different protein targets. The core of our approach involves using biophysical binding assays to characterise compounds that are produced on small scale using parallel chemistry. This approach will enable better chemical probes to be developed more rapidly at lower cost than is currently possible.Read moreRead less
Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: sy ....Interrogating diarylquinoline toxicity with targeted organic synthesis. Bedaquiline is the only new first-line treatment with a new mechanism of action to treat TB in the last 40 years, approved by the FDA on 31 December 2012. Alarmingly, this compound, has significant toxicities. The hypothesis tested in this project is that decreasing lipophilicity and basicity in this class of compounds while retaining target affinity will decrease toxicity but retain anti-TB activity. The project aims to: synthesise novel heteroarylalkylamines distinct from bedaquiline and designed to be more polar, less basic, and metabolically more stable; and, test all successfully synthesised target compounds for mechanism-based anti-tuberculosis activity, hERG-mediated cardiotoxicity, metabolic instability, and phospholipidosis.Read moreRead less
BioPPSy: An open source BIOchemical Property Prediction SYstem. Computer software will be developed for the prediction of the pharmacokinetic properties of small molecules to assist in the development of new compounds with drug-like properties. The software will be made freely available to promote its use and further development.
Malaria is a major global health problem. The protein AMA1 plays a key role in the invasion of host cells by malaria parasites, and agents that inhibit this interaction prevent host cell invasion and thus represent leads for the development of anti-malarial drugs. We have identified a number of chemical scaffolds that target a key site on AMA1. In this project we will optimize these leads to generate potent ligands for this site and evaluate the efficacy of these ligands as anti-malarial agents.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100226
Funder
Australian Research Council
Funding Amount
$424,000.00
Summary
Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not curren ....Advanced molecular discovery and characterisation facility. Natural product drug discovery in Australia requires access to high throughput functional assays to guide the separation and of novel bioactives with therapeutic potential. By establishing the advanced molecular discovery and characterisation facility in an academic environment across two institutions, research programs in early drug lead discovery and characterisation will be accelerated. It will provide unique capabilities not currently available in Australia, and help Australian researchers remain internationally competitive in breakthrough science and frontier technologies. The research enabled by this facility will lead to development of new drug candidates by the emerging Australian biotechnology industry.Read moreRead less
Development of molecular markers for resistance to blackleg disease (Leptosphaeria maculans) in canola. Canola (Brassica napus) is a valuable oil seed crop grown in many parts of the world and contributes annually $A450 million to the Australian economy. The overall aim of this project is to develop molecular markers for blackleg resistance using Australian germplasm along with evaluation in Australian disease nurseries which are regarded worlwide to develop the highest levels of disease pressu ....Development of molecular markers for resistance to blackleg disease (Leptosphaeria maculans) in canola. Canola (Brassica napus) is a valuable oil seed crop grown in many parts of the world and contributes annually $A450 million to the Australian economy. The overall aim of this project is to develop molecular markers for blackleg resistance using Australian germplasm along with evaluation in Australian disease nurseries which are regarded worlwide to develop the highest levels of disease pressure. Once molecular marker systems are developed and evaluated, they will be applied to facilitate the selection of Nugrain's (Industry Partner) canola breeding programs. Any molecular markers and QTL developed for Australian cultivars would find commercial application in breeding programmes.Read moreRead less
Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaborati ....Identifying genes causing thermal evolution of ectotherm body size. Cold-blooded animals increase in body size as they are found in populations at greater distances from the equator. These patterns are due to populations adapting to temperature. The aim of this project is to identify the genes involved in this adaptation process. We will do this by taking advantage of a well-studied body size cline in the vinegar fly on the east coast of Australia, and by building on an international collaboration between a leading UK and two Australian research groups. In doing so we will provide an explanation at the molecular level for one of the great unresolved phenomena in biology: why do cold-blooded animals get bigger in the cold? The research also leads to the potential to manipulate body size in animals.Read moreRead less
A Multicentre Randomised Clinical Trial Of Physical Activity For The Treatment Of Patients With Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$773,752.00
Summary
The number of older adults living with Alzheimer's disease (AD) will increase from 26.6 million to 106.2 million by 2050. In the absence of curative treatment options it is important to focus on non-pharmacological interventions such as physical activity. We propose to investigate whether a home-based physical activity program of 24 weeks for patients with AD can successfully decrease the rate of cognitive and functional declince and improve quality of life and psychological well-being.
Predictors And Correlates Of Health-related Quality Of Life And Morbidity In Overweight/obese Adolescents: Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$512,525.00
Summary
There is now no doubting the size and long-term risks to health of the childhood obesity epidemic. However, very little research has examined at population level its immediate consequences for mental health and physical functioning, what pathways confer risk and protection for these consequences, and their likely healthcare consequences. This study will utilise an existing cohort of approximately 1500 Victorian adolescents followed since childhood to examine neglected aspects of the genesis and ....There is now no doubting the size and long-term risks to health of the childhood obesity epidemic. However, very little research has examined at population level its immediate consequences for mental health and physical functioning, what pathways confer risk and protection for these consequences, and their likely healthcare consequences. This study will utilise an existing cohort of approximately 1500 Victorian adolescents followed since childhood to examine neglected aspects of the genesis and impacts of overweight and obesity. The Health of Young Victorians Study was originally assembled in 1997 when the children were in Grades Prep-3. In addition to information on putative risk and protective factors for overweight-obesity and direct measures of height and weight, it is unique in having collected data on health-related quality of life (HRQoL) since children were first recruited during the early primary school years. Eight years after the first wave, the children will be adolescents in Grades 8-11. This third wave will retain a focus on HRQoL. Innovations include study of potential emotional, behavioural and physical consequences of childhood obesity that may in turn affect the natural history of obesity. This large, population-based longitudinal study will redress neglected aspects of child and adolescent overweight-obesity specifically identified in 2003 by the NH and MRC. As well as establishing whether a range of common problems are related to overweight-obesity, it will be able to shed light on mechanisms of adverse outcomes associated with adolescent overweight-obesity, and study protective factors predicting remitting overweight from childhood to adolescence that may inform preventive activities. The study will make an international contribution to knowledge about pathways, prevalence and preventive opportunities for child and adolescent overweight-obesity.Read moreRead less