Identifying Glaucoma Risk Variants In The Norfolk Island Genetic Isolate
Funder
National Health and Medical Research Council
Funding Amount
$658,447.00
Summary
Primary open angle glaucoma is the most common form of glaucoma. In this project we will focus on the identification of functional genetic variants influencing development of this disorder, using a powerful whole exome sequencing approach in a large multigenerational pedigree from the Norfolk Island population isolate. The identification of genes influencing glaucoma development would provide invaluable clues to aid in defining the pathophysiology of this common disease.
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.
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.
Investigating Cytoskeletal Dynamics Across The Lifecycle Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$387,741.00
Summary
During its lifecycle the malaria parasite must cross tissues and invade cells in two very different hosts - humans and mosquitos. Although the molecules that drive this process are known, we know nothing about their dynamics in live parasites. Here, we will use state-of-the art microscopy and genetics to dissect parasite motility, tracking proteins in the parasite cell on their journey from human host through to the mosquito - utilising the first Australian malaria-dedicated insectary.
The glomerulus is the filtering component of the kidney. In many diseases, it can be the target of an inappropriate inflammatory response. As part of this response, white blood cells accumulate in the glomerulus where they cause damage. The aim of the project is to determine how these white blood cells accumulate in the glomerulus, specifically asking the question, what molecules present on the white blood cells and the glomerular blood vessels are required for this accumulation?
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100992
Funder
Australian Research Council
Funding Amount
$448,237.00
Summary
New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to devel ....New methods to capture protein dynamics of the TSC-mTOR signalling axis. Protein flexibility, the way proteins move, has a major role in how they function. However, we still do not have the tools to analyse this flexibility. Our cells have evolved many complex and flexible systems to sense and respond to their environment. For example, the TSC-mTOR system is found across life, from baker’s yeast to humans, however it remains poorly understood. This proposal will study TSC as an exemplar to develop novel machine-learning approaches to capture protein flexibility and shape. This proposal will advance fundamental understanding of the TSC-mTOR pathway and build transformative methodologies to study flexible proteins more broadly.Read moreRead less