Characterising Novel Alternative Splicing Networks That Promote Tumour Cell Plasticity
Funder
National Health and Medical Research Council
Funding Amount
$609,329.00
Summary
During cancer progression, tumour cells can change their properties and become more aggressive and resistant to therapies. We have identified an important regulator of this tumour cell transition, called “Quaking”, which causes widespread changes in gene splicing. We aim to investigate how "Quaking" causes changes in gene splicing and what the effects of these splicing changes are in tumour cells.
About one in eight known genetic disorders involve DNA alteration that activates a cellular quality control mechanism that disables the affected gene. This mechanism is more efficient in some individuals than others. It can influence disease outcomes and severity. We will engineer and apply tools and models to measure and manipulate this crucial cellular mechanism. This will allow us to predict disease severity as well as to intervene where a manipulation of this mechanism will be beneficial.
The Role Of UPF3B And Nonsense Mediated MRNA Decay Surveillance In The Pathology Of Intellectual Disability.
Funder
National Health and Medical Research Council
Funding Amount
$789,954.00
Summary
Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundam ....Proper functioning of the nonsense mediated mRNA decay (NMD or 'mRNA police') is crucial for any cell to ensure normal development and function. When NMD is compromised the outcome is learning and memory problems, autism or schizophrenia. Under this project we study malfunctioning NMD using stem and neuronal cells derived from patients' skin cells. Some of the affected genes might be considered for therapeutic interventions. NMD is relevant to 1000s of human disorders and as such it is of fundamental importance.Read moreRead less
Improved methods for quantitation of acute phase proteins in biological samples. Using monoclonal antibodies and fluorescence polarisation, we aim to develop improved quantitative analytical methods that are superior to the current clinical assays. The initial targets will be C-reactive protein (CRP) and serum amyloid precursor protein (SAP), but the technology should be readily adaptable to other serum proteins. Better assays for CRP and SAP will greatly facilitate improved clinical management ....Improved methods for quantitation of acute phase proteins in biological samples. Using monoclonal antibodies and fluorescence polarisation, we aim to develop improved quantitative analytical methods that are superior to the current clinical assays. The initial targets will be C-reactive protein (CRP) and serum amyloid precursor protein (SAP), but the technology should be readily adaptable to other serum proteins. Better assays for CRP and SAP will greatly facilitate improved clinical management of those at risk of heart attack, the single biggest contributor to healthcare costs in Australia. We further aim to adapt this technology to enable "point-of-care" assays that would help medical practitioners, especially in rural areas, to make informed diagnoses immediately.Read moreRead less
Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success ....Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success and health of offspring. The outcomes will inform development of new diagnostic assays for male fertility, and underpin strategic design of novel fertility treatments and products with applications in the human health and animal breeding industries. Read moreRead less
Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and c ....Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and cutting-edge directed evolution methodologies. Intended outcomes include enhanced institutional capacity for interdisciplinary collaboration; discovery of fundamentally important bacterial sensors; and development of synthetic regulatory circuits enabling outgrowth of non-biological biocatalysis industries.Read moreRead less
Site-specific protein functionalisation at diselenides via photocatalysis . This project aims to develop a new photocatalytic reaction for the on demand functionalisation of proteins. The synthetic methodology will solve a major technological gap in the field by enabling efficient access to proteins with defined modifications at specific locations. Functionalised proteins generated in the project will underpin a detailed understanding of how specific modifications influence the structure and fun ....Site-specific protein functionalisation at diselenides via photocatalysis . This project aims to develop a new photocatalytic reaction for the on demand functionalisation of proteins. The synthetic methodology will solve a major technological gap in the field by enabling efficient access to proteins with defined modifications at specific locations. Functionalised proteins generated in the project will underpin a detailed understanding of how specific modifications influence the structure and function of several important proteins. The project will generate significant new knowledge in the fields of chemistry and biology and will foster interdisciplinary collaboration, nationally and internationally. The breakthrough technology also has the potential to benefit Australia’s biotechnology sector.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101863
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these en ....Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these enzymes. Such inhibitor probes will provide critical information for potential therapeutic applications in human conditions associated with oxidative stress such as ageing, cancer, and heart disease.Read moreRead less
A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough ....A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough and responsive hydrogel platform from this disordered protein family through greater understanding of structure and mechanical function and incorporating adequate stiffness, strength and biocompatibility. Such tough hydrogels would be applicable to a range of biotechnological applications (eg intervertebral disc repair or artificial skin tissue engineering).Read moreRead less