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The role of redox balance and reactive oxygen species in beer stability using an integrated transcriptomic and metabolomic analysis. A better understanding of yeast redox balance will enable it to be used to predict fermentation outcomes and to link raw materials and processes to the quality of the final product. These data will produce economies in the brewing industry by the introduction of quality control regimes for raw materials and can be extrapolated to the wine industry. This will prov ....The role of redox balance and reactive oxygen species in beer stability using an integrated transcriptomic and metabolomic analysis. A better understanding of yeast redox balance will enable it to be used to predict fermentation outcomes and to link raw materials and processes to the quality of the final product. These data will produce economies in the brewing industry by the introduction of quality control regimes for raw materials and can be extrapolated to the wine industry. This will provide real economic advantage to Carlton and United Breweries which is an Australian company that has an international profile within a highly competitive industry.Read moreRead less
Application of functional genomics to study early fermentation parameters and flavour development in industrial fermentations. The aim of this research is to use genome-wide analyses to identify yeast genes involved in flavour compound production in order to manipulate the flavour profiles of industrial fermentations. This will identify those metabolic pathways and cellular processes that are important in the maintenance of flavour production during fermentation and give extensive insight into t ....Application of functional genomics to study early fermentation parameters and flavour development in industrial fermentations. The aim of this research is to use genome-wide analyses to identify yeast genes involved in flavour compound production in order to manipulate the flavour profiles of industrial fermentations. This will identify those metabolic pathways and cellular processes that are important in the maintenance of flavour production during fermentation and give extensive insight into the way metabolism changes during the fermentation process. Flavour is a major component of the product of fermented beverages and its development and maintenance in the finished product is of primary concern to the brewing and wine industries. This research will lead to a more competitive Australian-owned company with a major stake in the beer and wine industry.Read moreRead less
Functional Analysis Of The Molecular Switch That Regulates ADAM10-mediated Cleavage Of RTK Ligands In Tumour Cells.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
We have determined the structure and identified the region of the ADAM10 metalloprotease that controls its specific cleavage of ephrins. Ephrins and their receptors (Ephs) direct cell positioning during development by controlling cell-cell adhesion and repulsion. In adult tissues these proteins are present at low levels but are found at high levels in human cancers, including skin cancers, where they are thought to promote aggressive tumours. The switch to cell repulsion occurs by cleavage of th ....We have determined the structure and identified the region of the ADAM10 metalloprotease that controls its specific cleavage of ephrins. Ephrins and their receptors (Ephs) direct cell positioning during development by controlling cell-cell adhesion and repulsion. In adult tissues these proteins are present at low levels but are found at high levels in human cancers, including skin cancers, where they are thought to promote aggressive tumours. The switch to cell repulsion occurs by cleavage of the ephrin by ADAM10 which also functions in other cancer promoting events by cleaving growth factors. Our structure reveals how Eph-bound ephrin is specifically targeted by ADAM. We will now determine the relevance of this mechanism for other ADAM10 targets, and design drugs to bind this region and inhibit ADAM function, which we will test in assays measuring tumour cell movement and growth, with the aim of developing therapies to block cancer progression.Read moreRead less
Reduced Water Consumption in Commercial Malting Processes. The successful outcome for the project will be the production of barley varieties that can be successfully malted with a single steep, rather than the conventional two steeps currently employed. The objective will be achieved through the reduction of cell wall beta-glucan in barley grain. This will result in water savings of around 40%, or 1,500 megalitres per annum, for the Australian malting industry. The 1,500 megalitres saving in ....Reduced Water Consumption in Commercial Malting Processes. The successful outcome for the project will be the production of barley varieties that can be successfully malted with a single steep, rather than the conventional two steeps currently employed. The objective will be achieved through the reduction of cell wall beta-glucan in barley grain. This will result in water savings of around 40%, or 1,500 megalitres per annum, for the Australian malting industry. The 1,500 megalitres saving in water use would be sufficient to support the domestic water consumption of 30,000 people, based upon the use of 140 litres per person per day that was recently achieved in Brisbane.Read moreRead less
Infectious diseases are one of the leading causes of death and morbidity worldwide. In the last two decades the incidence of diseases caused by bacteria has increased dramatically with old pathogens re-emerging, often in a more virulent form, and new infectious agents appearing. Many pathogenic microbes are becoming increasingly resistant to antibiotics so that the need for new therapeutic targets is urgent. We will develop new antimicrobial chemotherapies by targeting DsbA, a specific factor in ....Infectious diseases are one of the leading causes of death and morbidity worldwide. In the last two decades the incidence of diseases caused by bacteria has increased dramatically with old pathogens re-emerging, often in a more virulent form, and new infectious agents appearing. Many pathogenic microbes are becoming increasingly resistant to antibiotics so that the need for new therapeutic targets is urgent. We will develop new antimicrobial chemotherapies by targeting DsbA, a specific factor involved in the generation of bacterial virulence. This protein is found in most bacteria and contributes to pathogenicity by promoting the formation of toxins and virulence factors. We will design specific inhibitors of DsbA by using a structure-based approach, implementing the leading edge technologies of fragment-based lead discovery by crystallography and NMR. We will then optimise the fragments to develop lead compounds and evaluate their suitability as DsbA inhibitors by in vitro and in vivo assays.Read moreRead less
Cytoprotection By Erythropoietin In Hypoxia-ischaemia Of The Kidney And Brain
Funder
National Health and Medical Research Council
Funding Amount
$477,661.00
Summary
We aim to make a significant research impact by describing the complex mechanisms responsible for protecting kidney and brain cells from stress caused by a lack of oxygen. In particular we will establish whether the compound erythropoietin (Epo), which occurs naturally in the human body but its human recombinant form can also be used as a treatment, may be useful in protecting cells from death following a shortage of oxygen. . We have already described how Epo can protect the kidney, but no one ....We aim to make a significant research impact by describing the complex mechanisms responsible for protecting kidney and brain cells from stress caused by a lack of oxygen. In particular we will establish whether the compound erythropoietin (Epo), which occurs naturally in the human body but its human recombinant form can also be used as a treatment, may be useful in protecting cells from death following a shortage of oxygen. . We have already described how Epo can protect the kidney, but no one has yet described its action on kidney cell differentiation or its effect on structural and vascular support in the injured kidney. When might Epo treatment be effective? Could it protect against chronic renal disease? Likewise, whilst more very pre-term babies survive, this is a crucial period when they are at heightened sensitivity to lack of oxygen and they are at risk of brain damage and poor development because of lack of maturation of key structural cells in the brain. The role of Epo in aiding brain cell maturation and on blood vessel formation and function in this faulty development period is not known. Both of these health problems are major issues causing huge costs to society both financial and emotional. Despite the early evidence of a useful role for Epo in human disease treatment, current experimental and clinical data demonstrate the importance of further thorough investigation of mechanisms and cellular pathways that will underpin improvements in clinical outcomes. A particular strength of our project is that by comparing similarities and differences in the kidney and brain, we will be able to elucidate the mechanisms of action of Epo and its analogues.Read moreRead less
Structural And Drug Discovery Studies Of Oxidative Stress Regulator, Thioredoxin-interacting Protein
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Toxic oxygen molecules known as Reactive Oxygen Species (ROS) are by-product of normal metabolism. The excess of ROS is damaging and is well known to contribute to ageing process and age-related diseases such as cancer, diabetic complications, immune-system decline, and cardiovascular conditions to name a few. The human body possesses several defense systems that protect us from the excess of ROS maintaining a healthy level of ROS. A down-regulator of one of this systems, a protein called TXNIP, ....Toxic oxygen molecules known as Reactive Oxygen Species (ROS) are by-product of normal metabolism. The excess of ROS is damaging and is well known to contribute to ageing process and age-related diseases such as cancer, diabetic complications, immune-system decline, and cardiovascular conditions to name a few. The human body possesses several defense systems that protect us from the excess of ROS maintaining a healthy level of ROS. A down-regulator of one of this systems, a protein called TXNIP, has been recently discovered. The amount of TXNIP is increased in such conditions as high glucose, a first sign of diabetes, and under ischemia, a shortage of blood supply occurring during heart attack. This weakens the anti-oxidant defense systems and makes the organism more vulnerable to ROS exposure. Our team of researchers embarked on structural and functional studies of TXNIP with the purpose to identify small molecules that can interfere with the undesirable action of TXNIP. These molecules might become useful therapeutic agents to counteract weakening organism's ROS defense system caused by TXNIP in many disease conditions such as, cancer, diabetes and cardiac failure.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454170
Funder
Australian Research Council
Funding Amount
$187,341.00
Summary
Biacore3000-Expansion of Proteomics Facility. The sequencing of the human genome has led to redirection of effort towards the rapid characterisation of the products of genes, proteins. This project will establish state of the art facilities for protein identification and characterisation in the Hunter Region. The investigators are representative of several major research programs and are unified by their specific expertise in the fundamental molecular mechanisms underlying the control of cellula ....Biacore3000-Expansion of Proteomics Facility. The sequencing of the human genome has led to redirection of effort towards the rapid characterisation of the products of genes, proteins. This project will establish state of the art facilities for protein identification and characterisation in the Hunter Region. The investigators are representative of several major research programs and are unified by their specific expertise in the fundamental molecular mechanisms underlying the control of cellular processes in plants, animals and humans. Understanding these mechanisms will provide the basis for improved management of the environment and pathological conditions through identifying molecular targets for diagnosis, genetic manipulation or drug design.Read moreRead less