Ubiquitin And SUMO DNA Damage Response Signalling At Deprotected Telomeres During The Cell Cycle
Funder
National Health and Medical Research Council
Funding Amount
$302,627.00
Summary
Following genome damage cells stop the cell division process and initiate DNA repair. We discovered that at specific times during cell division his does not happen if the damage signals originate from the chromosome ends (i.e. “telomeres”). We anticipate this is necessary to prevent genomic instability in healthy cells and may be driving genomic instability in cancer cells. Experiments described here will elucidate the molecular mechanisms and biological significance of our observation.
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.
Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably e ....Chromosomes are structures that carry genes in all our cells. Every human cell has 46 chromosomes. In the nucleus of eukaryotic cells, DNA is highly folded and compacted with specific proteins into a dynamic polymer called chromatin. Gene expression, chromosome division, DNA replication, and repair all act, not on DNA alone, but on this chromatin template. The discovery that enzymes can (re)organise chromatin into accessible and inaccessible configurations revealed mechanisms that considerably extend the information potential of the genetic code. In addition, it is now established that chromatin structural features can influence gene expression. In vitro studies support a model in which chromatin functions as a barrier for the access to DNA. Therefore this organization has to be tighly regulated and dynamic to allow the protein-DNA interactions critical for nuclear functions. Importantly genome organisation provides in addition to genetic information another layer of information, so called epigenetic, which by definition means that it is stably inherited throughout cellular divisions, yet it is not encoded genetically. Thus each cell type will display a specific epigenome. We have recently constructed small human minichromosomes, which are much easier to study than the much larger normal chromosomes. The present project proposes to define the epigenetic feature across an entire human chromosome using our minichhromosomes as working models. The outcome will be a significant gain in our knowledge on the processes underlying epigenetic regulation, the organisation of specialised chromatin domain, and behaviour of the chromosomes.Read moreRead less
Robust Data-Driven Control for Safety-Critical Systems. This project aims to develop new approaches to controlling robotic and cyber-physical systems in safety-critical applications. This project expects to generate new knowledge in how to harness the power of machine learning for robot control, while guaranteeing safety and stability at all times. The outcomes of this project will be new algorithms and a deeper understanding of the interplay of data, learning, and models, as well as experimenta ....Robust Data-Driven Control for Safety-Critical Systems. This project aims to develop new approaches to controlling robotic and cyber-physical systems in safety-critical applications. This project expects to generate new knowledge in how to harness the power of machine learning for robot control, while guaranteeing safety and stability at all times. The outcomes of this project will be new algorithms and a deeper understanding of the interplay of data, learning, and models, as well as experimental validation on a surgical robot and a bipedal walking robot. This project will provide significant benefits by dramatically increasing the range of applications in which the power of machine learning can be safely applied to advance the capabilities and uptake of robotics.Read moreRead less
Control and learning for enhancing capabilities of quantum sensors. This project aims to develop new theories and algorithms to enhance capabilities in engineering quantum sensors from the perspective of systems and control. The project is significant because it is anticipated to advance key knowledge and provide systematic methods to enable achievement of high-precision sensing for wide applications, e.g., early disease detection, medical research, discovery of ore deposits and groundwater moni ....Control and learning for enhancing capabilities of quantum sensors. This project aims to develop new theories and algorithms to enhance capabilities in engineering quantum sensors from the perspective of systems and control. The project is significant because it is anticipated to advance key knowledge and provide systematic methods to enable achievement of high-precision sensing for wide applications, e.g., early disease detection, medical research, discovery of ore deposits and groundwater monitoring. The intended outcomes are fundamental theories, effective control and learning algorithms for achieving highly-sensitive sensors. These outcomes should make important contributions to and deliver new knowledge and skills for Australia's sensing industries, which could benefit Australia's economic growth.Read moreRead less
The Role Of Arousal And Respiratory Control Factors In The Pathogenesis Of Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$567,924.00
Summary
Sleep apnoea (OSA) is a very common breathing disorder in sleep characterized by repetitive closure of the collapsible portion of the throat with serious effects on sleep quality and health. Basic causes of OSA are still largely unknown. We will investigate waking responses to breathing load and related respiratory control factors that we believe may be fundamental causes of OSA, and potentially explain many features of OSA including worsening in light sleep and with increasing age.
Distributed Estimation, Control and Optimisation for Networked Systems. This project aims to study large scale networked systems in major infrastructures including power networks, transportation networks, internet of things, and other cyber-physical systems. This project is expected to develop new methodology and algorithms for distributed estimation, control and optimisation of these systems. Distributed solutions are essential because traditional techniques which were designed for small system ....Distributed Estimation, Control and Optimisation for Networked Systems. This project aims to study large scale networked systems in major infrastructures including power networks, transportation networks, internet of things, and other cyber-physical systems. This project is expected to develop new methodology and algorithms for distributed estimation, control and optimisation of these systems. Distributed solutions are essential because traditional techniques which were designed for small systems are not suitable for efficient operations of large scale systems. Application examples include distributed state estimation for power networks, control of multi-agent systems and optimal scheduling of transportation networks. The outcomes of this project are vital to the understanding and management of these systems. Read moreRead less
Mass-production of beneficial insects for commercial pest management - physicochemical definition of oviposition sites for development of cost-efficient artificial substrates. The mass-production of beneficial insects for commercial purposes demands the development of cost-effective techniques for breeding and distributing them to growers. Many predatory beneficial insects lay their eggs in sites that prevent effective mass culturing. To circumvent this difficulty, it should be possible to defin ....Mass-production of beneficial insects for commercial pest management - physicochemical definition of oviposition sites for development of cost-efficient artificial substrates. The mass-production of beneficial insects for commercial purposes demands the development of cost-effective techniques for breeding and distributing them to growers. Many predatory beneficial insects lay their eggs in sites that prevent effective mass culturing. To circumvent this difficulty, it should be possible to define such oviposition sites in chemical and physical terms, and then use the information to develop artificial substrates that are convenient for mass rearing the insects and for disseminating them to growers. We will use the mealybug predator Cryptolaemus montrouszieri to test the feasibility of this approach and to assess its application to other beneficial species.Read moreRead less
A New Approach to Sampled-Data Control Design for Nonlinear Systems. This project aims to exploit new sampling and sampled-data modelling insights to bridge the continuous/sampled-data gap in the control of nonlinear systems. The goal is to investigate the impact of these insights on the control design problem and provide a new class of digital control laws for continuous time non-linear systems.
Renewable energy generation from flow-induced vibration. Much engineering effort has been expended to eliminate vibration of marine structures. This project seeks to provide the basis for the development of tidal energy harnessing, by deliberately amplifying and harnessing vibration. This technology offers the promise of capturing clean, zero-emissions energy, while presenting no risk to marine life.