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.
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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
In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-ski ....In depth characterisation of the gamma delta T cell immune synapse. This project aims to comprehensively characterise the activation principles of gamma delta T cells. These cells have an understudied but central role in vertebrate immunity and development. A missing piece of the puzzle is how gamma delta T cells sense stress and how this signal leads to activation. Expected outcomes include the generation of fundamental knowledge in immunology and structural biology. This proposal uses high-skilled techniques, including cryo-electron microscopy and single-molecule imaging and holds ancillary benefits to postgraduate students. Anticipated outcomes include influential publications, building a critical mass of expertise in Australia and fostering international collaborations with Australia at the epicentre.Read moreRead less
Preclinical Development Of A Therapeutic Anticancer Antibody To C-Met
Funder
National Health and Medical Research Council
Funding Amount
$435,530.00
Summary
Many common cancers cannot be effectively treated. A range of these cancers (e.g. gastric and lung cancer) display the molecule c-Met on their cell surface. c-Met promotes tumour growth; therefore, blocking c-Met is a promising strategy for treating these cancers. However, no antibodies or drugs that target c-Met have been licensed. The therapeutics that are being developed to target c-Met all have considerable limitations. Thus, there is an opportunity to develop a 'best-in-class' therapeutic.
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.
Utilization Of Gene-engineered T Cells For Enhancing Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$761,656.00
Summary
Killer T lymphocytes can penetrate tumours and their transfer into cancer patients has demonstrated some encouraging results, but this form of therapy and other approaches including vaccination remain ineffective in most cancer patients. In this project, we propose to improve the tumour trafficking and anti-tumour activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells, whilst minimizing toxicity to normal tissue.
New Strategies For Enhancing Chimeric Antigen Receptor (CAR) T Cell Therapy For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$849,540.00
Summary
The role of the immune system in cancer is now recognised as highly important, highlighted by the success of immunotherapy in patients. Yet many patients fail to respond to this form of treatment due to low frequency of lymphocytes present at the tumor site. A new form of immunotherapy involving transfer of gene-modified lymphocytes is a potential way to overcome this problem. This project will explore new strategies to enhance the utility of this approach against blood and solid cancers.
Generating Stronger And Smarter T Cells For Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$310,332.00
Summary
White blood cells from cancer patients can be modified in the laboratory to react against tumours. These cells can then be given back to the patient, which can sometimes cause cancer regression. However, often the white blood cells lack strength, or they lack the ability to distinguish between tumour and normal tissues of the body. In this project we seek to make stronger and smarter white blood cells that can deliver a lethal hit against tumours without damaging essential organs of the body.