Seeking causes of unexplained respiratory illness in children by identifying new respiratory viruses. Many respiratory illnesses including the common cold, ear infections, asthma attacks, the flu and pneumonia have no known cause even after all specimen testing is complete. This project will use 'virus hunting' experience to find and sequence as-yet-undiscovered viruses from such specimens so that they can be studied in more detail.
Lived experiences of treatment for hepatitis C in Australia. This project aims to support uptake of new hepatitis C treatments. With the introduction of new treatments in 2016, the Australian Government adopted the WHO’s goal of eliminating the disease by 2030. While early treatment rates were high, they have since plateaued, with stigma and poor information considered key obstacles. This project will generate new knowledge on treatment decisions and experiences, using a proven qualitative metho ....Lived experiences of treatment for hepatitis C in Australia. This project aims to support uptake of new hepatitis C treatments. With the introduction of new treatments in 2016, the Australian Government adopted the WHO’s goal of eliminating the disease by 2030. While early treatment rates were high, they have since plateaued, with stigma and poor information considered key obstacles. This project will generate new knowledge on treatment decisions and experiences, using a proven qualitative methodology. In doing so, it will produce a website covering personal experiences of treatment, issues in treatment decision-making, and advice on enhancing life on treatment and after. It will tackle hepatitis C-related stigma, and inform and benefit potential treatment users, families and relevant professionals.
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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.
Discovery Early Career Researcher Award - Grant ID: DE220100165
Funder
Australian Research Council
Funding Amount
$451,900.00
Summary
Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include gener ....Engineering T cells to promote peripheral immunity. Tissue-resident memory T cells (TRM) are key for immune protection against infections and cancer. This has led to much interest in understanding how these immune cells develop, although elucidation of molecules that regulate TRM are still scarce. This project aims to (i) identify genetic drivers of TRM in peripheral organs and (ii) modulate TRM generation utilising state-of-the-art genetic engineering techniques. Expected outcomes include generating new knowledge that will contribute to the development of novel therapeutics against infectious disease and cancer, together with the benefit of promoting national and international collaboration with the ultimate goal of improving health.Read moreRead less
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less
Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
The natural function and evolution of an essential parasite transporter. This project aims to resolve the natural function and evolution of a transporter essential to the survival of malaria and other parasites. Malaria and its sibling Apicomplexan parasites cause devastating diseases in humans and livestock across the world. Much remains to be understood about these parasites, and options for controlling them are diminishing. The project will interrogate the functions of the transporter protein ....The natural function and evolution of an essential parasite transporter. This project aims to resolve the natural function and evolution of a transporter essential to the survival of malaria and other parasites. Malaria and its sibling Apicomplexan parasites cause devastating diseases in humans and livestock across the world. Much remains to be understood about these parasites, and options for controlling them are diminishing. The project will interrogate the functions of the transporter proteins. The knowledge gained might help to combat Apicomplexan parasites by targeting these transporters’ native functions.Read moreRead less
Experimental co-evolution of Yeast and E. coli. This project aims to measure the rates and genetic mechanisms of adaptation for individual species within a microbial community. Expected outcomes of this interdisciplinary project include the first genomic and phenotypic dataset of a model microbial community, and novel tools for the analysis of meta-genomic datasets. This project has the potential to transform understanding of microbial adaptation.
Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensi ....Molecular basis of synergy between PIs and defensins against fungi. The plant defensin nicotinamide adenine dinucleotide dehydrogenase subunit 1 (NaD1) has potent antifungal activity against agricultural and human pathogens and has potential in the treatment of serious diseases that affect crop production and human health. NaD1 has been found to permeabilise membranes and allows entry of other molecules into the fungal cytoplasm. While screening for molecules that enhance the activity of defensins a number of proteinase inhibitors were identified that act synergistically with NaD1. This project aims to identify the molecular basis of this synergy which is expected to lead to better control of fungal diseases of crops and in humans.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