Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100097
Funder
Australian Research Council
Funding Amount
$675,000.00
Summary
An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and c ....An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and crystallisation techniques, including second order nonlinear imaging of chiral crystals (SONICC) imaging and lipid cubic phase approaches, to enable structural studies to be undertaken on challenging proteins. This information is often used for the rational development of therapeutics. The facility would support cutting-edge biological research In Australia.Read moreRead less
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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Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on rec ....Understanding endogenous allosteric modulators of G protein-coupled receptors. Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100037
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
A cellular nano-imaging facility: Probing cellular complexity. Answering the major medical and biotechnology questions of the 21st century will be heavily reliant on the use of advanced imaging techniques. This facility will establish a new and revolutionary microscope which is capable of producing images of living cells in action at high magnification and with the greatest clarity.
Expression and substrate recognition by MARCH ubiquitin ligases. Eukaryotic cells are compartmentalised, with different organelles playing distinct functions. This project will characterise the MARCHs, proteins which control the localisation and half-life of other proteins. Understanding how the MARCHs work will provide novel insights into fundamental cellular processes that play major roles in many biological functions.
Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by an ....Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by animals (in venoms and immunity), fungi (in defence) and pathogenic bacteria (in disease). The aim of this project is to image to the highest possible resolution how the MAC form pores in the context of bacterial cells and explore the way it inserts into cells in real time. Intended project outcomes may lay the foundation for applied future research into improved antibiotic delivery and novel pesticide development.Read moreRead less
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Identification of the molecular targets on filamentous fungi that lead to specific recognition and killing by an antifungal plant defensin. Tobacco flowers naturally produce potent antifungal molecules for protection against disease. The purpose of this project is to understand why these molecules are so toxic to fungal pathogens with a view to using them for control of fungal diseases in crops and humans.
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