Development of Chemoenzymatic Methods for the Selective Elaboration of Polyfunctionalised Therapeutic Agents to Oligomers with Improved Efficacy. The aims of the project are to screen a novel collection of genetically engineered enzymes for their capacity to selectively manipulate proven therapeutic agents so that, ultimately, much more potent polymeric derivatives of the agent/drug can be obtained. The combined use of enzyme libraries and chemical manipulations to generate more powerful polymer ....Development of Chemoenzymatic Methods for the Selective Elaboration of Polyfunctionalised Therapeutic Agents to Oligomers with Improved Efficacy. The aims of the project are to screen a novel collection of genetically engineered enzymes for their capacity to selectively manipulate proven therapeutic agents so that, ultimately, much more potent polymeric derivatives of the agent/drug can be obtained. The combined use of enzyme libraries and chemical manipulations to generate more powerful polymeric variants of already established drugs has never been undertaken previously in Australia. This approach has the capacity to generate hitherto inaccessible classes of therapeutic entities and to provide a new and unique technology platform for the country's biotechnology industry.Read moreRead less
Chemical Synthesis and Biological Evaluation of Analogues of Platencin, a New-generation Antibiotic. The just discovered natural product platencin displays potent and broad spectrum anti-bacterial activity. It may represent the precursor of a new class of drugs to replace current anti-infective agents which are becoming alarmingly less effective as bacterial resistance increases dramatically. For this reason, platencin has been described as a once in a generation discovery. This study will explo ....Chemical Synthesis and Biological Evaluation of Analogues of Platencin, a New-generation Antibiotic. The just discovered natural product platencin displays potent and broad spectrum anti-bacterial activity. It may represent the precursor of a new class of drugs to replace current anti-infective agents which are becoming alarmingly less effective as bacterial resistance increases dramatically. For this reason, platencin has been described as a once in a generation discovery. This study will exploit two sophisticated new synthetic techniques for the purposes of making analogues of platencin that will be screened by the industry partner, Biota, for anti-bacterial properties. New drug candidates capable of treating especially dangerous infections such as methicillin resistant staphyllococcus aureus (MRSA) should thus emerge.Read moreRead less
Chemoenzymatic Routes to Novel Dendritic Architectures Suitable for Pharmaceutical Applications. Dendritic molecules incorporating multiple copies of a particular functional group on their periphery allow for attachment of drug-like molecules at each of these sites. The resulting conjugates often have vastly superior therapeutic properties relative to the original single drug molecule. This phenomenon is now revolutionizing drug design. Developments in this area are limited by the range of dendr ....Chemoenzymatic Routes to Novel Dendritic Architectures Suitable for Pharmaceutical Applications. Dendritic molecules incorporating multiple copies of a particular functional group on their periphery allow for attachment of drug-like molecules at each of these sites. The resulting conjugates often have vastly superior therapeutic properties relative to the original single drug molecule. This phenomenon is now revolutionizing drug design. Developments in this area are limited by the range of dendritic molecules currently available. Thus, lack of variation in the three-dimensional architecture and the functionality available at the periphery of such constructs is a serious deficiency. This proposal seeks to redress this through the application of novel chemoenzymatic methods developed by the applicant.Read moreRead less
The Development of New, Non-steroidal Anti-Asthma Drugs with Novel Modes of Action. Asthma represents one of Australia's most significant chronic disease states. It adversely affects the lives of many hundreds of thousands of citizens and represents a growing problem, especially amongst younger members of the population. The start-up biotech company Cryptopharma has recently identified a family of steroid derivatives that deliver, through a novel mode of action, significant anti-asthma activity ....The Development of New, Non-steroidal Anti-Asthma Drugs with Novel Modes of Action. Asthma represents one of Australia's most significant chronic disease states. It adversely affects the lives of many hundreds of thousands of citizens and represents a growing problem, especially amongst younger members of the population. The start-up biotech company Cryptopharma has recently identified a family of steroid derivatives that deliver, through a novel mode of action, significant anti-asthma activity in in-vivo models. The purpose of the present work is to develop, through comprehensive synthetic organic chemistry and medicinal chemistry-type studies, non-steroidal analogues of Cryptopharma's lead compound that can be used clinically in the treatment of asthma.Read moreRead less
Developing new methods to retrieve and analyse preserved genetic information. This project will position Australia at the leading edge of research into preserved DNA, and will use innovative molecular biology approaches to develop a range of new forensic, archaeological and medical applications. It will build Australian knowledge and scientific capacity by developing core expertise and training personnel in areas important for biosecurity, customs and quarantine, forensics/counter-terrorism, and ....Developing new methods to retrieve and analyse preserved genetic information. This project will position Australia at the leading edge of research into preserved DNA, and will use innovative molecular biology approaches to develop a range of new forensic, archaeological and medical applications. It will build Australian knowledge and scientific capacity by developing core expertise and training personnel in areas important for biosecurity, customs and quarantine, forensics/counter-terrorism, and studies of climate change. It will also create and foster research innovation in molecular biology with spin-offs for evolution, archaeology, medical and conservation biology research, and will also encourage involvement with the rapidly expanding field of genomics and bioinformatics.Read moreRead less
Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS rese ....Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS research including epidemiology, immunology and neurobiology. Collaboration of 8 major Australian institutions is also important for this project and future studies. The team will have access to a new national MS GeneBank (platform) with samples from 2240 patients that should generate findings important to world-wide MS genetic knowledge.Read moreRead less
Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucida ....Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucidate whether there is any association between RRV strain and the severity of human disease. It will also identify viral markers that could assist public health officials in determining likely disease outcomes of outbreaks and could provide new avenues for the design of antiviral strategies.Read moreRead less
Reducing health disparities for culturally and linguistically diverse peoples. This project aims to develop a greater understanding of migrants and the factors that predict poor health outcomes related to blood-borne viruses and sexually transmitted infections. The delayed access by migrants to healthcare from culturally and linguistically diverse backgrounds results in late diagnosis, low treatment uptake, and poorer health outcomes, with enhanced risk of infection and increased burden on the h ....Reducing health disparities for culturally and linguistically diverse peoples. This project aims to develop a greater understanding of migrants and the factors that predict poor health outcomes related to blood-borne viruses and sexually transmitted infections. The delayed access by migrants to healthcare from culturally and linguistically diverse backgrounds results in late diagnosis, low treatment uptake, and poorer health outcomes, with enhanced risk of infection and increased burden on the health system. The data collected in this project will assist in developing health services to meet these needs.Read moreRead less
Modelling and control of mosquito-borne diseases in Darwin using long-term monitoring. Management of mosquito populations is a high public health priority because these insects can spread diseases such as malaria, dengue, Ross River virus, Barmah Forest virus, Murray Valley encephalitis, Japanese encephalitis and Kunjin/West Nile virus. Our research into the effectiveness of mosquito control programs in Darwin is of immediate national relevance and priority given the need to Safeguard Australia ....Modelling and control of mosquito-borne diseases in Darwin using long-term monitoring. Management of mosquito populations is a high public health priority because these insects can spread diseases such as malaria, dengue, Ross River virus, Barmah Forest virus, Murray Valley encephalitis, Japanese encephalitis and Kunjin/West Nile virus. Our research into the effectiveness of mosquito control programs in Darwin is of immediate national relevance and priority given the need to Safeguard Australia from invasive diseases. There is an urgency to undertake our research because global environmental change and increasing movements of people (particularly military personnel) from overseas regions where these diseases are endemic is increasing the vulnerability of northern Australia to the (re)establishment of mosquito borne diseases.Read moreRead less
Digging deeper to improve yield stability. This project aims to provide innovative breeding solutions that harness the ‘hidden’ part of the plant, roots, to support the development of more productive crops in the face of climate variability. The project expects to generate new insights into the biology and genetics of root development in barley, a model cereal crop, by applying cutting-edge genome editing, phenotyping and genomics technologies. Anticipated outcomes include novel methodologies to ....Digging deeper to improve yield stability. This project aims to provide innovative breeding solutions that harness the ‘hidden’ part of the plant, roots, to support the development of more productive crops in the face of climate variability. The project expects to generate new insights into the biology and genetics of root development in barley, a model cereal crop, by applying cutting-edge genome editing, phenotyping and genomics technologies. Anticipated outcomes include novel methodologies to accelerate breeding for diverse production environments, with direct applications in barley, and other major cereals including wheat and oats. This should provide significant economic and social benefits to the Australian grains industry through yield stability amidst climate variability.Read moreRead less