Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational ....Protein design. This project aims to design binding specificity in proteins in a rational way. Extending the existing repertoire of protein specificity using engineering principles should harness the catalytic power and high binding affinities of natural proteins. By building upon protein design algorithms, this project will develop biosensors for neurotransmitters and specialist enzymes to incorporate unnatural amino acids. It will iteratively improve the designs and algorithms by computational and experimental characterisation. The outcomes should address the long-standing need in synthetic biology for a facile route to designer proteinsRead moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100609
Funder
Australian Research Council
Funding Amount
$368,000.00
Summary
Mechanobiology: a new model of integrin activation by membrane tension. This project aims to address a fundamental question in mechanobiology on how integrin receptor coordinates with force to mediate cell spreading, migration, growth and survival. With an observation that membrane deformation enhances integrin binding, the project expects to establish a new model of integrin activation by membrane tension. It will develop an integrated approach combining single-molecule force probes, super reso ....Mechanobiology: a new model of integrin activation by membrane tension. This project aims to address a fundamental question in mechanobiology on how integrin receptor coordinates with force to mediate cell spreading, migration, growth and survival. With an observation that membrane deformation enhances integrin binding, the project expects to establish a new model of integrin activation by membrane tension. It will develop an integrated approach combining single-molecule force probes, super resolution microscopy, microfluidics and molecular dynamics simulations. It is expected that the role of membrane tension in promoting cell adhesion will be defined at molecular scale, and the link between integrin activation and Piezo calcium channel mediated membrane tension sensing will be delineated.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100220
Funder
Australian Research Council
Funding Amount
$180,000.00
Summary
Fluorescence and internal reflection system to develop lab-on-chip devices. Fluorescence and internal reflection system to develop lab-on-chip devices:
The aim of this project is to develop and establish a state-of-the-art fluorescence imaging facility. It aims to establish a total internal reflection fluorescence microscope combined with high speed epifluorescence imaging workstation that will be tailored to specifically investigate the fundamentals of blood cell, and vascular cell function. T ....Fluorescence and internal reflection system to develop lab-on-chip devices. Fluorescence and internal reflection system to develop lab-on-chip devices:
The aim of this project is to develop and establish a state-of-the-art fluorescence imaging facility. It aims to establish a total internal reflection fluorescence microscope combined with high speed epifluorescence imaging workstation that will be tailored to specifically investigate the fundamentals of blood cell, and vascular cell function. The project forms part of a broad bioengineering research program aimed at developing novel lab-on-chip technologies for basic cell biology and haematology. Outcomes from these projects may have significant impact in fundamental research in both bioengineering and biology disciplines.Read moreRead less
Computational enzymology: exploring the free energy landscape of enzymatic catalysis. Most biochemical reactions depend on enzyme catalysis and understanding how enzymes work at the molecular level remains a central question. This project will develop a suite of computational models to study the mechanisms of enzyme-catalysed reactions and such knowledge holds promise for technological benefits in the form of new drugs and novel catalysts.
Understanding sub-cellular systems at the atomic level. By extending the range of biomolecular systems that can be modelled computationally at the atomic level the project will enable important biomedical processes such as how bacterial toxins penetrate cell membranes and how protein hormones transmit signals into cells to be understood in unprecedented detail.
Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project ....Engineering new tools to aid structure determination of membrane proteins. This project aims to address the inherent instability of G protein-coupled receptors (GPCRs), which are cell-surface proteins that are a major drug targets. The instability of GPCRs has resulted in a lack of atomic-level structural information that has hindered structure-based drug discovery efforts. This project expects to develop tools to improve GPCR stability and streamline the structure determination process. Project outcomes are intended to lead to significant advances in membrane protein structure determination and will have a substantial impact on future research in the pharmaceutical industry.Read moreRead less
Synthetic leukocytes: bio-inspired DNA nanorobots powered by flow. Inspired by the way white blood cells roll along blood vessel walls, our goal is to build DNA nanorobots that roll along surfaces in flow. We take a synthetic biology approach to using biomolecules, such as DNA and proteins, to build functional particles and surfaces. To achieve this, we will combine our teams’ technological advances in DNA nanotechnology, plasma-activation for biomolecule immobilisation, and microfluidic devices ....Synthetic leukocytes: bio-inspired DNA nanorobots powered by flow. Inspired by the way white blood cells roll along blood vessel walls, our goal is to build DNA nanorobots that roll along surfaces in flow. We take a synthetic biology approach to using biomolecules, such as DNA and proteins, to build functional particles and surfaces. To achieve this, we will combine our teams’ technological advances in DNA nanotechnology, plasma-activation for biomolecule immobilisation, and microfluidic devices. This project will contribute new methods for synthetic particle motion in flow and provide new insights into biomolecule interactions and motion. Ultimately, this will allow us to harness rolling for the delivery of synthetic nanorobots for detection and remediation in flow systems, such as the body.Read moreRead less
Structure And Function Of The Alternative Splicing Factor ZNF265
Funder
National Health and Medical Research Council
Funding Amount
$509,017.00
Summary
Now that the human genome has been sequenced, we can see that a human being is defined bye approximately 30000 genes. One of the biggest surprises to come from this work was that the number of genes was significantly smaller than many predicted. Similar surprise was registered at the discovery that the genome of the fruit fly actually contained fewer genes than that of the model worm, Caenorhabditis elegans. Part of the explanation for these apparent discrepencies lies in the phenomenon known as ....Now that the human genome has been sequenced, we can see that a human being is defined bye approximately 30000 genes. One of the biggest surprises to come from this work was that the number of genes was significantly smaller than many predicted. Similar surprise was registered at the discovery that the genome of the fruit fly actually contained fewer genes than that of the model worm, Caenorhabditis elegans. Part of the explanation for these apparent discrepencies lies in the phenomenon known as gene splicing, whereby one gene can actually give rise to many different isoforms of the same protein. These different isoforms can have different structures and-or functions, and dramatically increase the complexity that it is possible for an organism to achieve with a given number of genes. The process of splicing is very intricate, requiring precise control to allow an organism to develop normally. Many human genetic diseases are known to arise from problems with splicing. However, our understanding of the mechanisms of splicing is rather incomplete. This proposal aims to improve our understanding of the splicing process through a range of biophysical and molecular biological approaches. This information should prove useful in understanding human development and disease.Read moreRead less
The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.Read moreRead less