Glycointeractions. This project aims to characterise two new classes of structural interactions with carbohydrates: carbohydrate-carbohydrate interactions and short alpha helical domains which can bind carbohydrates. Carbohydrate structures are found on the surface of cells in all forms of life. The intended outcome is to understand the molecular basis for these carbohydrate interactions. This information should provide an intellectual framework for understanding and manipulating these carbohydr ....Glycointeractions. This project aims to characterise two new classes of structural interactions with carbohydrates: carbohydrate-carbohydrate interactions and short alpha helical domains which can bind carbohydrates. Carbohydrate structures are found on the surface of cells in all forms of life. The intended outcome is to understand the molecular basis for these carbohydrate interactions. This information should provide an intellectual framework for understanding and manipulating these carbohydrate interactions, which underpin many processes in biological systems. The findings will inform the design of future drugs to block these interactions and will generate new tools for glycoscience.Read moreRead less
Structural basis of the neuroendocrine enzyme GAD65-mediated autoimmunity in Type 1 Diabetes. More than 80 per cent of patients with Type 1 Diabetes develop antibodies against the neuroendocrine enzyme GAD65. This project will use state-of-the art techniques to study the interaction of GAD65 with antibodies in molecular detail. This will provide key insights into the molecular mechanisms of autoimmune disease.
Investigating the molecular basis of T-cell receptor cross-reactivity. This project will explore the basis of unexpected immune reactions whereby the immune system mistakes one molecular structure for another, a phenomenon known as cross-reactivity. This project will examine how often this is due to molecular mimicry, potentially explaining why immune T cells sometimes react inappropriately to different agents.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100179
Funder
Australian Research Council
Funding Amount
$3,189,000.00
Summary
Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein ....Automated high resolution and high contrast cryo -TEM for three-dimensional structural biology. This project aims to establish a facility in automated, single-particle cryo-TEM and cryo-TEM tomography (Titan Krios) that will enable atomic and molecular structure research and three-dimensional subcellular and cellular imaging. The project will span all multiscale cryo-TEM modalities from the visualisation of cells, membranes and macromolecular complexes, through to near-atomic-resolution protein structure determination. Cryo-single particle analysis and tomography are recognised as revolutionary technologies in molecular structural biology and powerful enablers of future ground-breaking discovery. The project will deliver significant competitive advantage for Australia in leading-edge structure-based research, drug discovery, new opportunities for applied research and development, and showcasing science to the public.Read moreRead less
The discovery and characterisation of novel protein regulators of blood cell formation. All of the mature blood cells in the human body are derived from a common ancestor cell type known as a stem cell. Our proposed studies will enhance our knowledge of how functional, mature blood cells are formed from stem cells and how dysregulation of these normally tightly controlled pathways can give rise to severe blood diseases.
Structural Investigations Of The Bcl-2 Family Cell Death Apparatus
Funder
National Health and Medical Research Council
Funding Amount
$612,652.00
Summary
Programmed Cell Death is a process by which dangerous cells are removed from the body. Sometimes it goes wrong and causes disease, e.g. cancer cells stay alive when they should die. This project will study a group of proteins that regulate cell death, the Bcl-2 family of proteins, in order to understand the mechanism by which they control the balance of cell life and death. The findings will inform the development of new drugs aimed at regulating cell death in a variety of disease states.
Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enz ....Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enzymes regulated by fat molecules that will be of great interest to researchers across many branches of life sciences. Expected outcomes and benefits will be deeper understanding of fat molecules as nutrient signalling metabolites, and how they influence cell metabolism, growth and development.Read moreRead less
The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a funct ....The structure of heteromeric amyloid fibrils with signaling activity. This project aims to determine the composition, structure and properties of important protein complexes involved in a newly identified cell death pathway known as necroptosis. This cell death pathway removes unwanted or damaged cells during development or infection. These necroptosis protein complexes are unusual because they have a fibrillar amyloid structure, contain more than one protein type in the fibrils and have a functional, signalling role. The research will determine how these fibrils form and how the structures confers biological function. It could identify features in these fibrils that can be targeted as a means of ultimately preventing tissue damage after heart attack and stroke.Read moreRead less
Inhibiting protein-protein interactions involved in neural development and disease. This project will determine the molecular mechanisms by which the protein LMO4 (a regulator of brain development) binds to DEAF1 (which also regulates neural development) and CtIP (which protects against tumour formation). This will allow a set of reagents to be developed to help determine the functions of LMO4, and may ultimately be used to treat disease.
Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from c ....Crosstalk between cell survival and cell death pathways. This project aims to determine the precise molecular mechanisms underlying cell fate decisions. The dynamics between cell survival (autophagy) and cell death (apoptosis) are complex, involving significant crosstalk between these pathways. This is fundamentally important to cellular processes. Aberrant control of autophagy and apoptosis affects the function of all organisms as well as the development and treatment of diseases ranging from cancer to heart disease. This project endeavours to advance our understanding of the proteins that interconnect autophagy and apoptosis. The results are expected to explain how cells determine their fate and inform future development of strategies to treat disease.Read moreRead less