Cytotoxic lymphocytes are immune cells responsible for the killing infected or cancerous cells. How cytotoxic lymphocytes mature from a naive inactive to a fully activated state as they encounter infected or malignant cells is poorly understood, and will be investigated in the current proposal. Our results will aid in the development of novel therapies for cancer and other immunological diseases.
High-Throughput Discovery Of Synergistic Drug Combinations For Metastatic Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,526,568.00
Summary
Treatment outcomes for patients with metastatic bowel cancer remain poor, with most tumours developing resistance within 24 months. A key problem is that cancers are genetically diverse, with some cells inevitably resistant to any given treatment. This study aims to discover effective drug combinations targeting distinct essential tumour cell functions through robotics-based pairwise testing of known drugs on bowel cancer cell lines representing the genetic diversity of the disease.
Structural And Functional Characterisation Of The Oncogene P-Rex1
Funder
National Health and Medical Research Council
Funding Amount
$623,447.00
Summary
The spread of cancer to other parts of the body (metastasis) is a major cause of mortality. The characterisation of proteins that regulate metastasis is therefore a priority. P-Rex1 plays a crucial role in promoting metastasis in breast and other cancers. We will determine the structural basis of P-Rex1 activity, and investigate how its dysregulation promotes aberrant cell growth. This study will provide the knowledge to build future drug development programs targeting P-Rex1 in cancer.
Bile Acid And Neurosteroid Signaling To The Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$587,950.00
Summary
Defects in the secretion of bile into the intestine cause digestive diseases, and abnormal circulating levels of bile acids induce profound itch and abnormal pain sensation. This project examines whether a cell-surface receptor (TGR5) produced by intestinal and sensory neurons mediates actions of bile acids on intestinal functions, itch and pain. The project will define mechanisms of digestive and sensory disorders and identify new therapies for constipation, diarrhoea, itch and pain.
Molecular Targets Of Amino Acid/neurotransmitter Conjugates Of Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$846,390.00
Summary
This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these c ....This project investigates endogenous chemicals that affect cells important for detecting and responding to pain. We aim to discover how these compounds affect proteins important for nerve cell function, particularly proteins that have a prominent role in detecting and transmitting painful events. The compounds we examine are not themselves likely to be drugs, but future therapies may involve manipulating the levels of these chemicals in the body, or using drugs that mimic the activity of these compounds.Read moreRead less
Spinal Cord Injury Pain: Understanding Mechanisms To Develop Treatments
Funder
National Health and Medical Research Council
Funding Amount
$597,675.00
Summary
Spinal cord injury has devastating effects on health and quality of life. Many of the major consequences of injury, such as chronic pain and loss of voluntary voiding, are "invisible" – i.e., they are not as visible as limitations of mobility. Our study aims to define the neurobiological changes that cause development of persistent pain after spinal cord injury and use pharmacological tools to attenuate the development of pain.
Targeting Bone Marrow Mediated Angiogenesis And Metastasis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,006.00
Summary
Despite advances in treatment and diagnostics breast cancer (BC) remains one of the leading causes of death in women. Metastases and tumour blood vessel recruitment are linked. Work by Dr Mellick and others has shown that host bone marrow contributes endothelial progenitor cells (EPCs) to tumour vasculature. The chemokines and their receptors, which differentiate EPCs from tumour vessels, will be knocked down in the tumour cells and EPC progenitors with the aim of preventing tumour spread.
Defining Epigenetic Predictors Of Long-term Outcomes Of Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$409,408.00
Summary
On average, those born premature do worse health-wise than those born at term. However, some do worse than others. Our aim is to identify these people at birth to better help doctors and parents to closely monitor their health. For this, we will be “reading the diary of pregnancy” in the molecules added to chromosomes in blood during pregnancy in young adults with will characterised states of health. We will analyse DNA from blood that we will extract from stored heel prick spots.
A Phase III Trial Comparing Adjuvant Versus Salvage Radiotherapy For High Risk Patients Post Radical Prostatectomy
Funder
National Health and Medical Research Council
Funding Amount
$819,138.00
Summary
About half of all patients Treated with an operation to remove their prostate cancer have a high chance of the cancer coming back. Giving immediate radiotherapy to all patients will improve cure rates but does not benefit all men and can cause significant side effects. This study explores whether it is safe to wait and only give radiotherapy when there is a rising PSA after surgery indicating active cancer. A total of 470 men from Australasia will enter this study comparing the two approaches.
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.