Our current understanding of cellular signalling and disease is based on ensemble measurements over a cellular or molecular population. While these measurements have provided valuable information on the molecular circuitry required for cellular function, there is a lack of detail on the spatio-temporal dynamics of signal initiation and propagation at the single molecule and single cellular level. Single particle (molecule or cell) approaches offer the advantage of being able to detect individual ....Our current understanding of cellular signalling and disease is based on ensemble measurements over a cellular or molecular population. While these measurements have provided valuable information on the molecular circuitry required for cellular function, there is a lack of detail on the spatio-temporal dynamics of signal initiation and propagation at the single molecule and single cellular level. Single particle (molecule or cell) approaches offer the advantage of being able to detect individual processes including rare events that would be lost in an ensemble measurement. Moreover single particle approaches provide dynamic-kinetic information that does not rely on synchronising a population of molecules or cells. In this proposal we aim to build on our combined expertise in EGF-EGFR signalling, biophysics, biosensors, quantum dot nanotechnology and single molecule spectroscopy to learn more about how EGFR cellular signalling works and how it is impaired in cancer. This project will provide basic information that could lead to the design of more effective drugs directed agaisnt this therapeutic target.Read moreRead less
Novel Fluorogenic Probes For The Selective Detection Of Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$542,489.00
Summary
Current methods for the detection of multi-resistant organisms either require expensive instrumentation and expert analysts or are simple, but require 24-48 hours for bacterial identification. The ideal surveillance method would be cost effective, rapid, reliable, and simple to perform. This project aims to prepare a range of fluorescent substrates for incorporation into growth media which will then be evaluated for the specific identification of individual multi-resistant organisms, e.g. MRSA.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
Unravelling Mechanotransduction Pathways In The Heart
Funder
National Health and Medical Research Council
Funding Amount
$949,956.00
Summary
This project addresses the still unresolved question of involvement of mechanosensitive ion channels in heart hypertrophy and arrhythmias including ventricular arrhythmias. These pathological conditions are a cause of a broadening fiscal healthcare burden in Western societies. Consequently, investigating the role of this class of ion channels in heart disease presents a priority for medical science and a great opportunity to improve the health outcomes for the Australian people.
A Novel Diagnostic Method To Determine The Likelihood Of Kidney Fibrosis And Progressive CKD In Patients With Diabetes Mellitus And Other Forms Of Chronic Proteinuric Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,848.00
Summary
The project aims to develop a new non-invasive diagnostic method to detect patients with early CKD, a major health burden that is mainly driven by obesity and diabetes. It will specifically determine whether exfoliated tubular cells in the urine reflect kidney disease progression and hence provide a proof of concept on whether our newly developed hyperspectral technique can be used as a non-invasive diagnostic tool to identify patients with kidney disease.
Clinical Research Translation In Fluorescence-guided Surgery Of Brain Cancer: Developing A Surgical Endoscope With Enhanced Contrast
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
This proposal aims to improve the life expectancy of brain cancer patients by developing a new neurosurgical optical imaging device. The technology will transform the recently developed fluorescence-guided surgery procedure, where the tumour is endowed with artificial fluorescence. Our state-of-the art technology will enhance the fluorescence detection beyond visual perception to help remove hard-to-detect small cancer cell clusters, resulting in more accurate surgical removal of tumours.
The initial step of T cell activation of how the external ligand binding is translated to an increase of receptor phosphorylation at the cytoplasmic side is remain poorly understood. It is believed that the loss of immune recognition in cancer and over reactivity in auto-immune diseases are caused by abnormality of this transmembrane signalling transduction. Clarification of this molecular machinery can provide a molecular basis of those diseases and guidelines of more effective therapies.
Investigation Of Lipid-protein Interactions Of Mechanosensitive Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$409,785.00
Summary
Living organisms are imminently exposed to mechanical stimuli such as gravity, touch or sound. Sensing mechanical stimuli is therefore crucial for survival. One biological tool for sensing mechanical stress are the mechanosensitive ion channels that open in response to tension in cell membranes. We will study the interactions and coupling between membrane lipids and mechanosensitive ion channels. These interactions are essential for the function of these fascinating sensory biological molecules.
Venoms To Drugs: Characterizing The Molecular Interactions Between Venom Peptides And Ion Channels With A View To Rational Drug Design
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The conventional approach to drug development is reaching a state of crisis as it is producing fewer new drugs at increasing cost. A promising alternative is to harness the rich and diverse chemistry of venom peptides. This project aims to understand the mechanism by which venom peptides achieve their pharmacological activity. This knowledge is essential for venom-based drug design for treating diseases ranging from nervous systems disorders, stroke, chronic pain and psychiatric illnesses.