Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolut ....Single molecule intracellular intravital imaging of actin dynamics. The project intends to develop imaging technology to visualise fundamental processes in cells within a living animal. The focus will be on the actin cytoskeleton, a dynamic macromolecular machine involved in key cellular processes including cell structure, mobility and division. It is exquisitely sensitive to environmental perturbations, requiring it to be studied in cells in living tissue. The project aims to extend the resolution of live imaging to the single molecule to understand the dynamics of actin assembly with implications for cellular processes that are hijacked in diseases. It also aims to provide a novel assay that may enable testing of the impact of drugs on cellular processes in real time.Read moreRead less
The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
The rational design and construction of new genetic circuits for applications in synthetic biology. By designing, building and testing new gene control modules, this project will gain an understanding of the design principles required for the construction of biological circuits with predictable and controllable behaviour. The ability to build such circuits will have significant economic benefit in areas such as metabolic engineering and biomedicine.
Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be use ....Rational design of genetic circuits that respond to transient signals. Engineered genetic circuits with predictable and robust behaviour promise unprecedented environmental and economic benefits. Yet much work remains to be done before living devices can routinely be built from a standarised set of biological parts - the goal of synthetic biologists. By studying how natural genetic switch circuits respond to transient signals, this project aims to uncover a set of design rules which could be used to construct and control purpose-built genetic networks and pathways. The results of this project are expected to add to the molecular tookit available to synthetic biologists.Read moreRead less
Determination of cellular mechanisms underpinning cancer cell metastasis through integrated in vivo imaging approaches. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and in vivo model systems that mimic the disease, this project will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cel ....Structural domains of beta-tubulin and their role in microtubule dynamics and transport. This study aims to obtain a fundamental understanding of how the structural domains of the cytoskeletal protein beta-tubulin are involved in microtubule structures during cell division and vesicular transport. Using gene-editing technology and coupling this with cell biological approaches and high-resolution cell imaging will enable detailed analysis of the role of beta-tubulin domains in these important cellular processes. The outcomes will include fundamental new knowledge in cell biology and lead to the development of unique biological models that can be used to understand disease.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100620
Funder
Australian Research Council
Funding Amount
$378,000.00
Summary
Mechanisms of controlled gene expression in cells and organisms. The goal of this project is to reveal the nature of a cellular mechanism that has a major influence on gene expression in all eukaryotic cells. How gene expression is controlled is of fundamental importance to all life forms. The project plans to develop molecular tools that enable the visualisation and interrogation of this gene regulatory mechanism in live cells, tissues and whole organisms. The outcomes are anticipated to lead t ....Mechanisms of controlled gene expression in cells and organisms. The goal of this project is to reveal the nature of a cellular mechanism that has a major influence on gene expression in all eukaryotic cells. How gene expression is controlled is of fundamental importance to all life forms. The project plans to develop molecular tools that enable the visualisation and interrogation of this gene regulatory mechanism in live cells, tissues and whole organisms. The outcomes are anticipated to lead to an essential understanding of how cells respond to physiological and environmental cues by coordinating changes in gene expression, and to provide potential avenues towards manipulation for pharmaceutical, agricultural and biotechnology purposes.Read moreRead less
Unique epigenetic states in plant stem cell niches for safeguarding genome integrity. Plant stem cells are the foundation cells of all plant growth and development, including generation of the reproductive cells. Therefore, it is critical that stem cells defend against attacks that may damage the genome. A unique epigenetic state in plant stem cell niches has been discovered that may protect the genome from damage due to parasitic DNA elements. Using sophisticated genomics, genetics, and cellula ....Unique epigenetic states in plant stem cell niches for safeguarding genome integrity. Plant stem cells are the foundation cells of all plant growth and development, including generation of the reproductive cells. Therefore, it is critical that stem cells defend against attacks that may damage the genome. A unique epigenetic state in plant stem cell niches has been discovered that may protect the genome from damage due to parasitic DNA elements. Using sophisticated genomics, genetics, and cellular technologies, this project will investigate how stem cell epigenetic state is linked to genome defence, how environmental stresses can disrupt the defence system, and the role of the system in driving new genetic diversity. This knowledge is of high importance as agricultural crops enter an era of increasingly challenging conditions.Read moreRead less
Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itse ....Comprehensive characterisation of DNA demethylation pathways in vivo. This project aims to provide a better understanding of the roles that DNA methylation plays during embryonic development. DNA methylation is a major regulatory mark present in vertebrate genomes. It is well established that the genomic patterns of DNA methylation are being actively remodelled during vertebrate embryogenesis. Nevertheless, it remains unclear how these events impact gene regulation and embryonic development itself. This project expects to unravel the functional contributions of DNA methylation to vertebrate embryogenesis by using latest cutting-edge genomics techniques. The project will be carried out on the highly tractable zebrafish model system which allows for easy genetic manipulation of the desired sequences. This project aims to provide a better understanding of embryonic development of vertebrates, including humans.Read moreRead less