Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
ADAM Metalloprotease Inhibition For Treatment Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$770,925.00
Summary
Colorectal cancer (CRC) causes over 4000 deaths/year, typically from developing drug resistance and spreading to other organs (metastasis). These processes involve tumour cells called cancer stem cells (CSCs), which rely on specific cell surface proteins for survival and function. We are developing antibodies against one of these type of proteins, to test in mouse models of CRC. These already show promise in targeting CSCs and inhibiting drug-resistance and metastasis in mice.
Radiotherapy Treatment For Prostate Cancer - A Change In Practice Based On Direct Evidence For Targeting And Toxicity Effects Using Real Outcomes Data
Funder
National Health and Medical Research Council
Funding Amount
$555,129.00
Summary
Radiotherapy for prostate cancer treatment will be more effective when we have better knowledge of what patient anatomy needs to be targeted, and what needs to be avoided. This project will combine data collected during a large Australasian prostate cancer radiotherapy trial, ‘RADAR’, with data collected using new patient imaging methods to determine how patient anatomy impacts on the effectiveness of their treatment and the side-effects they experience.
Alpha-particles linked to recombinant antibodies targeting tumour cells have potential to effectively treat tumours while minimising normal tissue side effects. We will explore a novel alpha-particle therapy approach to solid tumours, by delivering 225Ac directly into tumour cells, or into cells that support the tumour (microenvironment). This approach will hopefully result in development of a new approach to treatment of cancers that are resistant to conventional therapies.
Biofocussed Prostate Cancer RadioTherapy (BiRT): A Personalised Approach To Delivering The Right Dose To The Right Place
Funder
National Health and Medical Research Council
Funding Amount
$753,565.00
Summary
We propose a new approach to treating prostate cancer with radiotherapy to move from the standard whole prostate treatment to a personalised treatment that varies radiation intensity throughout the prostate. We will mathematically combine features that influence radiotherapy effect from advanced imaging, clinical and biopsy information. This model will map out the radiotherapy dose required at each part of the prostate, to maximise killing of the cancer whilst minimising harm to normal tissue
Humanisation And Pre-clinical Validation Of A Therapeutic Anti-cancer Antibody
Funder
National Health and Medical Research Council
Funding Amount
$699,136.00
Summary
This grant will develop a novel antibody against a protease expressed on cancer cells. Preclinical studies, and antibody humanisation, will be performed. This project will also provide vital information on optimal therapeutic approaches with the antibody that can be ultimately taken into human trials.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collecti ....Expanding the molecular tool set for structural studies of proteins and their complexes. Many applications in medical science and drug development depend on our ability to determine the 3D structures of proteins, protein assemblies and protein-ligand complexes. This project will develop novel lanthanide-binding tags and crosslinking agents that can be coupled to unnatural amino acids introduced into proteins with advanced protein chemistry techniques. These new tools will facilitate the collection of structure restraints by nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and mass spectrometry, which are needed to generate accurate models of proteins and their complexes with other molecules. Major beneficial outcome will include an increase in the number of protein targets amenable to rational drug design and improved methods for generating new drug leads.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100122
Funder
Australian Research Council
Funding Amount
$725,000.00
Summary
Hydrogen-deuterium exchange system - a missing link in protein analysis . Proteins are highly dynamic molecules that are essential to life. This project aims to acquire a fully automated and integrated hydrogen-deuterium exchange system, a powerful tool for analysing the motion of proteins and their interactions with other molecules. Expected outcomes include a new capability for biology labs around Australia by (1) increasing success rates of difficult projects that aim to visualise 3D protein ....Hydrogen-deuterium exchange system - a missing link in protein analysis . Proteins are highly dynamic molecules that are essential to life. This project aims to acquire a fully automated and integrated hydrogen-deuterium exchange system, a powerful tool for analysing the motion of proteins and their interactions with other molecules. Expected outcomes include a new capability for biology labs around Australia by (1) increasing success rates of difficult projects that aim to visualise 3D protein structures and (2) providing rapid information about protein interaction sites. Anticipated benefits include the generation of dynamic data that will be highly complementary to static pictures of protein structures. This will enable clever design of new proteins with beneficial uses in the biotechnology industry.Read moreRead less