Structural Characterisation Of The Co-inhibitory Complex Formed By The Tumour Suppressor PTEN And The Metastatic Factor PREX2
Funder
National Health and Medical Research Council
Funding Amount
$563,602.00
Summary
Metastasis is a major cause of cancer mortality. Characterisation of key proteins that regulate metastasis is therefore a priority. PTEN and PREX2 are enzymes that play key roles in metastasis in melanoma, and other cancers. We will determine the structural basis of PTEN:PREX2 co-inhibition, and determine how cancer-associated PREX2 mutations dysregulate this inhibitory complex. This study will provide the necessary knowledge for future drug development programs targeting PTEN:PREX2 in cancer.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Targeting NDM-producing ‘superbugs’: Optimising Novel Combinations With ‘old’ Polymyxins Using Pharmacological, Molecular Imaging And Systems Biology Approaches
Funder
National Health and Medical Research Council
Funding Amount
$582,732.00
Summary
Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these ver ....Rapid global spread of so-called NDM-producing bacterial ‘superbugs’ is presenting a major medical challenge. Without new antibiotics under development, polymyxin is becoming the only effective antibiotic. Unfortunately we recently revealed that treatment with polymyxin alone can rapidly lead to resistance in NDM-producing ‘superbugs’. This project will employ new tools to optimise rational polymyxin combinations, thereby providing urgently needed information to clinicians for treating these very problematic infections.Read moreRead less
A Structural Understanding Of Class B G Protein-coupled Receptor Function
Funder
National Health and Medical Research Council
Funding Amount
$1,289,570.00
Summary
G protein-coupled receptors (GPCRs) are the largest family of cell surface proteins that enable communication from external signals to the inside of cells of the body. Class B GPCRs are a therapeutically important subclass of these receptors and they play crucial roles in bone and energy homeostasis, cardiovascular control and immune response. This grant will uncover fundamental knowledge on how these receptors work, and will enhance future development of therapeutics.
Electronic-vibrational spectroscopy: A new probe for structure and function. This project aims to solve a major challenge in ultrafast spectroscopy: to identify and quantify competing reaction pathways in complex photochemical systems. Ultrafast Spectroscopy provides information on excited-state processes of photochemical reactions, however, unravelling heterogeneous systems with competing parallel processes remains difficult. Multidimensional electronic-vibrational spectroscopy, sensitive to el ....Electronic-vibrational spectroscopy: A new probe for structure and function. This project aims to solve a major challenge in ultrafast spectroscopy: to identify and quantify competing reaction pathways in complex photochemical systems. Ultrafast Spectroscopy provides information on excited-state processes of photochemical reactions, however, unravelling heterogeneous systems with competing parallel processes remains difficult. Multidimensional electronic-vibrational spectroscopy, sensitive to electronic dynamics and molecular structure, is expected to overcome this barrier. This new level of detail will profoundly enhance our understanding of energy and chemical conversion in complex systems and will reveal design targets for optimising next-generation light-energy harvesting, conducting, and emitting materials.Read moreRead less
Structural Events In Insulin And IGF Signalling - A Nanodisc Approach To A Problem In Cancer, Diabetes And Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$752,403.00
Summary
Insulin and its insulin-like growth factors play a major role in three major disease states facing ageing Australians—diabetes, cancer and Alzheimer's disease. We aim to understand how these proteins send messages into cells via their so-called receptors. We will isolate the receptor molecules from cells and then image them in an advanced electron microscope to produce three-dimensional images. Our findings will have implications for the design of therapeutics targeting the above three diseases.
Material Properties of Nanocrystals. The mechanical characteristics of nanocrystals determine the viability of many novel applications and devices emerging from the field of nanotechnology. Despite their fundamental importance, the mechanical properties of these nanocrystals is only vaguely understood, because their size has prohibited their measurement. In this project, we shall investigate the mechanical properties of these materials for the first time using a combination of theoretical modell ....Material Properties of Nanocrystals. The mechanical characteristics of nanocrystals determine the viability of many novel applications and devices emerging from the field of nanotechnology. Despite their fundamental importance, the mechanical properties of these nanocrystals is only vaguely understood, because their size has prohibited their measurement. In this project, we shall investigate the mechanical properties of these materials for the first time using a combination of theoretical modelling, atomic force microscopy, and a new form of spectroscopy that allows the actual deformation of nanocrystals to be measured. The fundamental scientific knowledge gained is expected to impact on the development of current and future nanodevices.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100137
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
Femtosecond broad wavelength range laser facility. This facility will provide a unique source of ultra-short laser pulses spanning the X-ray to the infrared regions. It will provide a powerful coherent X-ray source that will position Australia at the forefront of coherent imaging science and the ability to perform ultrafast infrared spectroscopic measurements.
Integrated Multidimensional Gas Chromatography - Spectroscopic Detection Methodology for Chemical Marker Discovery. Chemical species are pervasive in our modern society and are found in personal care products, foods, additives, petroleum products, illicit drugs, pharmaceuticals and pollutants. Each sample must be analysed to determine its accurate composition, and as a safeguard. This requires chemical methods of analysis. Classical chemical methods may fail when samples become too complex, or t ....Integrated Multidimensional Gas Chromatography - Spectroscopic Detection Methodology for Chemical Marker Discovery. Chemical species are pervasive in our modern society and are found in personal care products, foods, additives, petroleum products, illicit drugs, pharmaceuticals and pollutants. Each sample must be analysed to determine its accurate composition, and as a safeguard. This requires chemical methods of analysis. Classical chemical methods may fail when samples become too complex, or they may lead to imprecise identification. This Frontier Technologies proposal has broad national and international relevance through development of new methods for authentication of chemical identity and the subsequent superior ability to characterise numerous sample compositions.Read moreRead less