Unravelling The Mechanism Of MHC Class-I Associated Drug Hypersensitivities
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Some drugs cause adverse reactions that are life threatening. We think these reactions are mediated by killer T cells as they are genetically controlled by immune response genes that normally guide immunity to microbes. We will study immune reactions to the drug abacavir, used to treat HIV (AIDS); allopurinol used to prevent gout and carbamazepine, used to treat epilepsy. The study may also help devise better treatments for patients who experience severe forms of these reactions.
Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for ....Exploring the gene regulation networks governing mitochondrial biogenesis in Arabidopsis. Mitochondria, subcellular organelles that perform many functions indispensable to plant growth and productivity, are dynamic compartments whose protein complement changes dramatically during plant development and under stress. Yet, the cellular processes that regulate the production of these organelles are virtually unknown. By combining conventional approaches with an extremely powerful holistic method for simultaneously examining the expression patterns of every gene in the model plant Arabidopsis, this project will identify proteins that regulate mitochondrial biosynthesis and uncover the gene networks that these proteins control. The project outcomes will provide new opportunities for the rational manipulation of plant growth and productivity.Read moreRead less
Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide ....Genome Approaches to Investigate Metabolic Coordination in Plant Cells. Metabolism of C and N in legume nodules requires interaction between the symbiotic bacteria and plant organelles, particularly metabolism in plastids and mitochondria. Fixed N is assimilated through the de novo synthesis of purines in both plastids and mitochondria. However, each of the nine pathway enzymes is encoded by a single gene, indicating each protein is targeted to both organelles. Purine metabolism will provide a model to assess the more general occurrence of dual-targeted proteins in plants. The aim is to identify and eventually exploit the signalling mechanism(s) that mediate communication between plastids and mitochondria.Read moreRead less
Optimisation Of Antimicrobial Therapy For Severe Bacterial Infections In Neonates And Young Children In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$943,865.00
Summary
This study aims to provide important information on the way young Papua New Guinean children with serious bacterial infections handle antibiotics, including newer agents that may be required if bacterial resistance is confirmed or increases. The data will be used to optimise treatment, thus reducing mortality and potential adverse drug effects, in PNG nad other tropical countries, and may have implications for the developed world as well.
Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and ....Arabidopsis DNA binding proteins that control transcription of its mitochondrial genome. The increases in crop output and quality needed to drive the agricultural sector of Australia's future economy will arise from knowledge gained by combining traditional methods and the type of cutting-edge research that identifies plant mitochondrial DNA-binding proteins and their sites of action. Mitochondria are fundamental to many agronomically important traits, including plant growth, fruit ripening and plant stress and disease defence. Opportunities for the rational manipulation of these and hitherto undiscovered traits will come from new knowledge generated by this project, which will develop and use frontier technologies that will keep Australia at the forefront of international research into mitochondrial structure and function.Read moreRead less
Molecular Pharmacology Of Chemokine Receptor Signalling In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$371,770.00
Summary
Molecular pharmacology is the study of how hormones, neurotransmitters and pharmaceuticals interact with our cells through receptors, which transfer a signal across the cell membrane to change the function of that cell. Chemokine receptors are recognised to play a role in the development of many cancers. Understanding how these receptors work has enormous implications for improving our ability to develop better anti-cancer treatments with fewer side effects.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
A proteomic approach to identifying the signaling pathway(s) by which acute oxidative stress causes cell death by apoptosis. Oxidative stress following traumatic injury (heart attack or stroke) is known to activate signaling pathways leading to programmed cell death (apoptosis). The aim of this project is to develop methods to identify the signaling proteins involved. Identifying proteins involved in causing cell death will be useful in developing diagnostic tools as well as providing potential ....A proteomic approach to identifying the signaling pathway(s) by which acute oxidative stress causes cell death by apoptosis. Oxidative stress following traumatic injury (heart attack or stroke) is known to activate signaling pathways leading to programmed cell death (apoptosis). The aim of this project is to develop methods to identify the signaling proteins involved. Identifying proteins involved in causing cell death will be useful in developing diagnostic tools as well as providing potential therapeutic possibilities.Read moreRead less
Protein modifications in plant mitochondria: towards functional proteomics. Energy production within plants in cellular structures called mitochondria is vital for their growth and development and is central to the early success of germinating and growing seedlings. This project intends to analyse mitochondria within plants using state of the art instrumentation and technologies. The findings from this research have the potential to directly flow into the plant biotechnology industry and could a ....Protein modifications in plant mitochondria: towards functional proteomics. Energy production within plants in cellular structures called mitochondria is vital for their growth and development and is central to the early success of germinating and growing seedlings. This project intends to analyse mitochondria within plants using state of the art instrumentation and technologies. The findings from this research have the potential to directly flow into the plant biotechnology industry and could assist the future development of Australian agriculture through genetic improvements. The expertise developed by this work will ensure that Australia is well placed to exploit future advances in this field and to further generate the development of novel biotechnological applications in agriculture.Read moreRead less
A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conduct ....A hierarchical quantum mechanical and classical simulation of biological ion channels. I aim to develop a methodology incorporating molecular quantum
mechanics and classical Brownian mechanics in a way that can be
applied practically to large macromolecular systems, thus relating
fine structural details to experimentally measurable
properties. Specifically, I will apply this methodology to study ion
channels in which the challenge is to relate electronic and atomic
structure to the conductance properties of the channel. Accurately
determining these relationships provides a pathway to developing cures
for many neurological, cardiac, and muscular diseases.
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