Fragment based screening to deliver drugs targeting tuberculosis and the gametocyte and liver stages of Plasmodium. This project will identify natural products that bind to critical proteins in malaria and tuberculosis to discover new ways to treat these diseases.
Biology and evolution of intracellular parasitism. This project will investigate the development of intracellular parasitism in environmental amoebae. The outcomes of this work will help to understand the mechanisms by which bacteria have evolved to survive inside cells and in some cases cause disease.
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
Discovery Early Career Researcher Award - Grant ID: DE140101728
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabo ....The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabolic adaptation, differentiation of cell types and the evolution of new gene expression outputs in distinct biological species. The outcomes will include new insights into the regulation and evolution of posttranscriptional gene networks. Read moreRead less
Epigenetic regulation in bacteria. This project aims to understand the effect of DNA modification on gene regulation in the bacterial organism Escherichia coli, which causes urinary tract infection worldwide. High-throughput DNA sequencing technologies mean one can determine the entire genetic blueprint of a bacterium – its genome – accurately, quickly and cheaply. Single-molecule real-time sequencing provides a complete read-out of a bacterial genome (genetic data) and chemical modifications of ....Epigenetic regulation in bacteria. This project aims to understand the effect of DNA modification on gene regulation in the bacterial organism Escherichia coli, which causes urinary tract infection worldwide. High-throughput DNA sequencing technologies mean one can determine the entire genetic blueprint of a bacterium – its genome – accurately, quickly and cheaply. Single-molecule real-time sequencing provides a complete read-out of a bacterial genome (genetic data) and chemical modifications of the DNA (epigenetic data). Epigenetic data can affect regulation: how genes are switched off and on. This project seeks to harness the power of single-molecule DNA sequencing, together with state-of-the-art genomic and molecular approaches, to better understand the impact of DNA modification on gene regulation in the model bacterial organism, Escherichia coli. This work will support advanced training in bioinformatics and microbiology and improve our understanding of regulation in all bacteria.Read moreRead less
The protein O-glycosylation pathway in Neisseria meningitidis. Neisseria meningitidis causes bacterial meningitis, a sudden and severe disease of particular concern to children in both the developed and developing worlds. This project will contribute to an understanding of how these bacteria evade the immune system by modifying the proteins displayed on their surface, which will help in the development of a vaccine.
Peril and promise: Origins and spread of integron gene cassettes. Integrons have a major role in spreading antibiotic resistance genes among pathogens. They do so by capturing gene cassettes encoding resistance, yet how these cassettes are generated, the taxa in which they originate, and the range of traits that cassettes can encode have been outstanding questions for 30 years. This project addresses these long standing questions. The project will analyze single bacterial cells to detect newly ....Peril and promise: Origins and spread of integron gene cassettes. Integrons have a major role in spreading antibiotic resistance genes among pathogens. They do so by capturing gene cassettes encoding resistance, yet how these cassettes are generated, the taxa in which they originate, and the range of traits that cassettes can encode have been outstanding questions for 30 years. This project addresses these long standing questions. The project will analyze single bacterial cells to detect newly generated cassettes and assign them to specific taxa, using an innovative method that links cassette DNA to bacterial 16S rDNA. Understanding cassette origins is the key to controlling their activity, both to harness integrons for biotechnology, and to prevent pathogens from acquiring new, dangerous traits. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100111
Funder
Australian Research Council
Funding Amount
$475,000.00
Summary
Expanding the Genomic Frontier - from Species to Strains and Individuals to Populations. Expanding the genomic frontier from species to strains and individuals to populations: The Ramaciotti Centre for Gene Function Analysis, a consortium of five universities, provides a large number of genomics and transcriptomics analyses. This project will establish an Ion Proton semiconductor-based sequencer and iScan platform to facilitate research breakthroughs in genomics, epigenomics, transcriptomics, an ....Expanding the Genomic Frontier - from Species to Strains and Individuals to Populations. Expanding the genomic frontier from species to strains and individuals to populations: The Ramaciotti Centre for Gene Function Analysis, a consortium of five universities, provides a large number of genomics and transcriptomics analyses. This project will establish an Ion Proton semiconductor-based sequencer and iScan platform to facilitate research breakthroughs in genomics, epigenomics, transcriptomics, and SNP analysis. Cell screening technology will also be established to allow the rapid analysis of cells of interest, prior to genomic / transcriptomic analysis. The increased data output, and concomitant reduction in analysis cost on the new platforms, will expand the genomics frontier, allowing researchers to fully analyse many strains from a single-celled species or many individuals from a population.Read moreRead less
Structure function analysis of the NusA-RNA polymerase interaction. Genes must be turned on at the right time, at the correct level in the appropriate cell in all organisms. This project will determine the role of an essential component of the process in bacteria called NusA. The results will apply to bacteria as well as higher organisms, and also have the potential to identify a new antibiotic target.
Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others a ....Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others are used in biotechnology for biosynthetic chemical production or bioremediation. This project expects to help the future development of new antibiotics and assist in the design of strains to be used in biotechnological applications.Read moreRead less