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
Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwante ....Novel peptide mimics for the disruption of chemical communication in bacteria. It is now well established that bacteria communicate with each other via small diffusible signalling molecules and coordinate their activities such as biofilm formation, swarming and expression of virulence factors in a coordinated manner. This project will investigate the synthesis of novel organic molecules that have the capacity to disrupt chemical communication in bacteria. This could allow control of the unwanted microbial activity without the use of growth inhibitory agents such as antibiotics, preservatives and disinfectants that select for the resistant organisms. This elegant approach to eradicating the virulence behaviour of microbes represents a novel strategy to combat antimicrobial resistance.Read moreRead less
Structure-based design of inhibitors of HIV-1 integrase. This project will produce compounds that block human immunodeficiency virus (HIV) replication. These compounds will benefit the 17000 Australians and more than 34 million people worldwide who are currently suffering with this terrible disease.
Development of small molecule primary sulfonamides as new drugs for malaria. Malaria is a major global health threat, causing approximately 800,000 deaths annually. Lives can be saved if patients are treated. The use of current antimalarial drugs is limited by drug resistance, low activity and poor safety. This project investigates the effectiveness of a new class of molecule as a safe drug treatment option to kill malaria parasites.
Rational design of new drug candidates for the treatment of Trypanosoma cruzi infection. There is a serious shortage of safe and effective drugs to treat Chagas disease which is caused by a parasitic infection. This project aims to design and identify new drug candidates by defining the disposition profile within the body which is necessary to achieve a therapeutic effect.
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 of bioactive natural substances from uncultured bacteria and their production using photosynthetic reactor technology. The range and rate of natural product discovery is the limiting factor in developing new therapies for cancer and infectious disease. This research will enable the discovery of new drugs, coupled to their production in a photosynthetic expression system. This represents a truly “green” and sustainable technology for the pharmaceutical industry.
Overcoming antibiotic resistance: rapid discovery of new antibacterial drug targets using chemical proteomics. The prevalence of multidrug-resistant bacteria in the community is a critical public health issue and there is an urgent and compelling need for new antibiotics with novel modes of action to combat these deadly superbugs. While antibiotics from nature have long been a mainstay of the pharmaceutical industry, their development as drugs can be challenging as their cellular targets and mod ....Overcoming antibiotic resistance: rapid discovery of new antibacterial drug targets using chemical proteomics. The prevalence of multidrug-resistant bacteria in the community is a critical public health issue and there is an urgent and compelling need for new antibiotics with novel modes of action to combat these deadly superbugs. While antibiotics from nature have long been a mainstay of the pharmaceutical industry, their development as drugs can be challenging as their cellular targets and modes of action are frequently unknown. In this project, innovative chemical proteomics approaches will be used to rapidly identify and characterise the cellular targets and modes of action of both newly discovered and historic antibiotic natural products, thereby overcoming this bottleneck and accelerating the development of next-generation antibiotics.Read moreRead less
Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular mic ....Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular microbiology. The outcomes are expected to be an increased understanding of bacterial DNA replication and mechanisms of antibiotic action and resistance. This project expects to generate new knowledge to assist in combatting antibiotic resistance in Gram-negative bacterial pathogens.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100482
Funder
Australian Research Council
Funding Amount
$364,536.00
Summary
Indoleamides as Molecular Interventions for Tuberculosis. This project aims to develop chemical probes capable of inhibiting the transport of essential mycolic acid across the cell wall of Mycobacterium tuberculosis. The emergence of resistant strains of Mycobacterium tuberculosis necessitates the identification of new, validated biological target(s) in the current control of tuberculosis. Preliminary data in this proposal demonstrate the discovery of indoleamides as a novel chemical entity. Dev ....Indoleamides as Molecular Interventions for Tuberculosis. This project aims to develop chemical probes capable of inhibiting the transport of essential mycolic acid across the cell wall of Mycobacterium tuberculosis. The emergence of resistant strains of Mycobacterium tuberculosis necessitates the identification of new, validated biological target(s) in the current control of tuberculosis. Preliminary data in this proposal demonstrate the discovery of indoleamides as a novel chemical entity. Development of these indoleamides may provide insights into a novel mechanism of action that could be targeted in combination with existing antitubercular agents.Read moreRead less