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Pharmacogenetic Investigations Of Glutathione Transferases
Funder
National Health and Medical Research Council
Funding Amount
$471,000.00
Summary
Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. This study will investigate (1)the genetic mechanisms that alter the production of glutathione transferases, (2) the character ....Members of the family of enzymes known as glutathione transferases are known to be responsible for the metabolism and detoxification of a wide range of compounds including therapeutic drugs and cancer causing chemicals. Genetic variation in an individual's compliment of glutathione transferases can alter their response to drug treatment or their susceptibility to cancer. This study will investigate (1)the genetic mechanisms that alter the production of glutathione transferases, (2) the characteristics of a new class of glutathione transferases and (3) the role of glutathione transferase A4 in protecting against disorders such as atherosclerosis and Parkinson's disease.Read moreRead less
Design And Use Of Human Hematopoietic Prostaglandin D2 Synthase Inhibitors In Allergic Asthma And Bone Diseases
Funder
National Health and Medical Research Council
Funding Amount
$517,960.00
Summary
Many currently used non-steroidal anti-inflammatory drugs are burdened by side effects such as gastrointestinal bleeding or increased risk of heart attack. This is because they ablate the production of a class of molecules called prostaglandins. We believe it is possible to fine tune the action of these drugs and reduce the side effect risk. There is evidence to suggest that only some prostaglandins are involved in inflammation, so the risk of side effect can be reduced by blocking the productio ....Many currently used non-steroidal anti-inflammatory drugs are burdened by side effects such as gastrointestinal bleeding or increased risk of heart attack. This is because they ablate the production of a class of molecules called prostaglandins. We believe it is possible to fine tune the action of these drugs and reduce the side effect risk. There is evidence to suggest that only some prostaglandins are involved in inflammation, so the risk of side effect can be reduced by blocking the production of only a small set. One prostaglandin, prostaglandin D2, is known to cause many characteristics of allergic asthma and may also contribute to osteoarthritis, although the evidence for this is contradictory. We will determine any therapeutic benefit to blocking the production of prostaglandin D2 in these diseases by developing compounds that only inhibit the enzyme responsible for its production.Read moreRead less
Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhi ....Pharmacological modification of retinal and visual function and relation to control of refractive error. Myopia (short-sightedness) affects many hundreds of millions of people worldwide and can lead to blindness. Drug treatments that prevent myopia are being developed, however there is no efficient way of determining who is at risk of myopia or who will benefit from these treatments. This fundamental research project will determine the retinal and visual effects of pharmacologic agents that inhibit myopia, with the aim of determining an ocular measure that is related to myopia, which is altered by drugs that are known to slow myopia progression, and that could be used as an indication of an agent's likely effectiveness.Read moreRead less
Controlling the spatial distribution of targeting ligands on dendrimer surfaces as a means of dictating cellular recognition and fate. This project seeks to develop next generation targeted drug delivery systems that 'home' to specific target cells, including cancers. Targeted delivery systems have the potential to revolutionise therapy by providing bespoke drug distribution patterns that are tailored to specific diseases and result in enhanced activity and reduced toxicity.
Enabling aerosol delivery of phages to defeat antibiotic-resistant bacteria. This project aims to explore the use of bacteriophages towards producing a safe, natural, and highly effective alternative to traditional antibiotics. Respiratory infections caused by multidrug-resistant Gram-negative bacteria are a major health problem worldwide, and cost Australia over $150 million annually. Some 5,000 Australians die each year from antibiotic resistant infections. The project aims to produce efficac ....Enabling aerosol delivery of phages to defeat antibiotic-resistant bacteria. This project aims to explore the use of bacteriophages towards producing a safe, natural, and highly effective alternative to traditional antibiotics. Respiratory infections caused by multidrug-resistant Gram-negative bacteria are a major health problem worldwide, and cost Australia over $150 million annually. Some 5,000 Australians die each year from antibiotic resistant infections. The project aims to produce efficacious and stable formulations of bacteriophages for easy delivery by inhalation as aerosols with a long shelf-life, making them a commercially viable product. The expected research outcome can lead to an economic and efficient technology to produce phage powders for novel treatment strategies of infections by inhalation.Read moreRead less
Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, ....Exploring metabotropic glutamate receptor 5 bias, allostery and heteromers. This project aims to provide novel mechanistic and structural insights into metabotropic glutamate receptor 5 (mGlu5) function. The mGlu5 is an essential regulator of neurotransmission and higher order brain functions including learning and memory. This project expects to expand knowledge of the fundamental biological processes engaged by mGlu5 through exploration of three novel paradigms of receptor activity: allostery, bias and heteromerisation. Expected outcomes also include generation of new pharmacological tools through interdisciplinary collaborative research between multiple institutions. There is significant expected economic benefit through commercialisation of new tools and facilitation of novel drug discovery.Read moreRead less
Allosteric Regulation Of G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
The normal function of all living cells depends on how they respond to the multitude of physical and chemical stimuli to which they are constantly exposed. The majority of these stimuli acting on cells do so not by directly entering the cells, but rather by acting on specific types of receiver proteins on the cell's surface that are called receptors. The most important family of cell-surface receptors transmit their message to the inside of the cell by coupling to yet another type of protein kno ....The normal function of all living cells depends on how they respond to the multitude of physical and chemical stimuli to which they are constantly exposed. The majority of these stimuli acting on cells do so not by directly entering the cells, but rather by acting on specific types of receiver proteins on the cell's surface that are called receptors. The most important family of cell-surface receptors transmit their message to the inside of the cell by coupling to yet another type of protein known as a G protein, and are therefore commonly referred to as G protein-coupled receptors (or GPCRs). Aberrations in the normal function of these GPCRs have been implicated in a wide variety of disorders, including neuropsychiatric conditions, endocrine disorders, cardiovascular disease and many cancers. To date, the majority of drugs acting at GPCRs do so by binding to specific regions on these receptors. Although many breakthroughs in disease treatment have been achieved using this approach, there remain a number of acknowledged limitations, including lack of drug selectivity, toxicity and reduced responsiveness with prolonged therapy. Our current proposal focuses on targeting drugs to alternative regions of GPCRs that may overcome many of the limitations associated with current drug therapies. An understanding of the properties of these alternative drug binding sites, which will be investigated in our current grant, can lead to more effective treatments for a variety of diseases.Read moreRead less
An attack from all angles! Multiphase particle systems that target respiratory infection. This project will result in advanced inhaled medicines for lung infection. Micron-particles will be engineered to have sustained drug release when deposited at sites of infection, yet avoid natural clearance and defence mechanisms. To study these systems, a series of characterisation, in vitro cell and in silico tools will be developed.