Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational ....Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational and experimental characterisation. The outcomes should address the long-standing need in synthetic biology for a facile route to designer proteinsRead moreRead less
Computational enzymology: exploring the free energy landscape of enzymatic catalysis. Most biochemical reactions depend on enzyme catalysis and understanding how enzymes work at the molecular level remains a central question. This project will develop a suite of computational models to study the mechanisms of enzyme-catalysed reactions and such knowledge holds promise for technological benefits in the form of new drugs and novel catalysts.
The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemis ....The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemistry and spectroscopy will be used. This will be the first time that the enzymes of bacterial Mn2+-oxidation will have been characterised in such detail and will lead to a greater understanding of the process of bacterial manganese oxidation.Read moreRead less
Structure And Function Of The Alternative Splicing Factor ZNF265
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
Now that the human genome has been sequenced, we can see that a human being is defined bye approximately 30000 genes. One of the biggest surprises to come from this work was that the number of genes was significantly smaller than many predicted. Similar surprise was registered at the discovery that the genome of the fruit fly actually contained fewer genes than that of the model worm, Caenorhabditis elegans. Part of the explanation for these apparent discrepencies lies in the phenomenon known as ....Now that the human genome has been sequenced, we can see that a human being is defined bye approximately 30000 genes. One of the biggest surprises to come from this work was that the number of genes was significantly smaller than many predicted. Similar surprise was registered at the discovery that the genome of the fruit fly actually contained fewer genes than that of the model worm, Caenorhabditis elegans. Part of the explanation for these apparent discrepencies lies in the phenomenon known as gene splicing, whereby one gene can actually give rise to many different isoforms of the same protein. These different isoforms can have different structures and-or functions, and dramatically increase the complexity that it is possible for an organism to achieve with a given number of genes. The process of splicing is very intricate, requiring precise control to allow an organism to develop normally. Many human genetic diseases are known to arise from problems with splicing. However, our understanding of the mechanisms of splicing is rather incomplete. This proposal aims to improve our understanding of the splicing process through a range of biophysical and molecular biological approaches. This information should prove useful in understanding human development and disease.Read moreRead less
Understanding sub-cellular systems at the atomic level. By extending the range of biomolecular systems that can be modelled computationally at the atomic level the project will enable important biomedical processes such as how bacterial toxins penetrate cell membranes and how protein hormones transmit signals into cells to be understood in unprecedented detail.
The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform ....The design and synthesis of angiotensin converting enzyme-2 (ACE2) inhibitors. A vast number of current drugs on the market are inhibitors of enzymes whose action needs to be controlled in order to treat many conditions. This proposal will apply our new approaches to the design of enzyme inhibitors with superior therapeutic action. The benefits of this research reside in new treatments for a range of cardiovascular diseases (the 3rd largest cause of mortality in Australia) and provide a platform for new biotech companies to be formed in Australia.Read moreRead less
Ancestral enzyme engineering for designer fat products. Consumers are increasingly turning to plant-based alternatives of meat and dairy products due to concerns about health, animal welfare and sustainability. Taste, nutritional profile, protein content and limited variety are barriers that continue to challenge food manufacturers. This project aims to develop a process for the fermentation of specialty food oils and fats from agriculture production waste, that can deliver the flavour and nutri ....Ancestral enzyme engineering for designer fat products. Consumers are increasingly turning to plant-based alternatives of meat and dairy products due to concerns about health, animal welfare and sustainability. Taste, nutritional profile, protein content and limited variety are barriers that continue to challenge food manufacturers. This project aims to develop a process for the fermentation of specialty food oils and fats from agriculture production waste, that can deliver the flavour and nutritional benefits of meat and dairy products when added to plant-based alternatives. The outcomes should valorise existing agriculture and food waste, converting waste materials into valuable food ingredients.Read moreRead less
Differential Expression Proteomics: Identification and Quantitation of Peptides and Proteins by Fixed Charge Derivatization and Tandem Mass Spectrometry. The aim of this proposal is to develop novel strategies for the rapid, sensitive and selective identification and quantitation of proteins present in complex mixtures. Specifically, isotopically labeled fixed charge derivatives of peptides containing selected amino acids will be developed that direct the formation of product ions following tan ....Differential Expression Proteomics: Identification and Quantitation of Peptides and Proteins by Fixed Charge Derivatization and Tandem Mass Spectrometry. The aim of this proposal is to develop novel strategies for the rapid, sensitive and selective identification and quantitation of proteins present in complex mixtures. Specifically, isotopically labeled fixed charge derivatives of peptides containing selected amino acids will be developed that direct the formation of product ions following tandem mass spectrometry toward a single fragmentation channel. This approach will provide enhanced selectivity and sensitivity of up to 2 orders of magnitude over existing approaches, and will allow examination, at the protein level, of the complex cellular changes that occur following transformation of cells from a normal to a diseased state.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