High-throughput genetic assays are commonly used to study the molecular basis of disease and such technology requires sophisticated data analysis methods that account for significant biological and experimental complexity. Specialized methods will be developed in free public software that will greatly benefit future genetic profiling studies.
Detection Of Cardiac Allograft Rejection By Peripheral Blood Gene Expression: A Novel Concept Of Personalized Approach To Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$292,705.00
Summary
Heart biopsy is required to detect rejection after heart transplantation. The cost of each biopsy is around $7,000 and at least 10 heart biopsies needed in the first post-transplant year alone. The biopsy is difficult for the patients and significant cost for the Australian healthcare system. Thus, it would be beneficial to identify rejection using a simple blood test. Such tool would help to reduce or eliminate the need for expensive heart biopsy and would reduce the cost by about 10 times.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
Role Of Hsp40 And Hsp70 In Huntingtin Misfolding, Oligomerization And Inclusion Assembly
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
Huntington disease results from a mutation that causes the Htt protein to become abnormally sticky and form toxic clusters in neurons. Cells have natural defences to clustering with proteins called chaperones, which are exciting therapeutic targets. This project will examine how chaperones defend against toxic Htt clustering with cutting-edge imaging technologies. The knowledge gained will aid in designing therapeutic strategies that stimulate the defence processes and suppress the clusters.
Developing Novel Molecules That Target Hormone Receptors As An Alternative Cancer Therapy
Funder
National Health and Medical Research Council
Funding Amount
$459,867.00
Summary
A promising class of cancer drugs target heat shock protein 90 (Hsp90) and prevent Hsp90 from maintaining its ~100 proteins involved in cell growth. However, all current Hsp90 chemotherapeutics non-selectively target proteins maintained by Hsp90, and induce a cell rescue mechanism involving Hsp70. We describe the development of a novel molecule that will selectively control cell growth and prevent cell rescue via a unique Hsp90 regulated mechanism.
Understanding Age-related Protein Aggregation. The Mechanism Of Cataract And Its Prevention
Funder
National Health and Medical Research Council
Funding Amount
$709,333.00
Summary
Cataract arises from clouding of the eye lens due to the aggregation of crystallin proteins whose high concentration and close packing facilitate lens transparency. This proposal will investigate crystallin structure and interactions to understand the reasons for cataract formation and its prevention via the design of aggregation inhibitors. The results will facilitate the development of drugs to prevent cataract and other related protein aggregation diseases, e.g. Alzheimer’s and Parkinson’s.
Disrupting Mucin-mucin Interactions To Treat Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$480,531.00
Summary
Diseases like asthma, emphysema and cystic fibrosis all feature the overproduction of mucus in the lungs that make it very difficult for patients to breathe and increases their susceptibility to infections. Few therapies are available for thinning this mucus, which is made thick by a network of linkages between proteins. We are studying these linkages and developing methods to break them up. This research could yield new mucus-thinning drugs to treat lung diseases.
Mechanisms Regulating Mitochondrial Outer Membrane Permeabilisation During Programmed Cell Death
Funder
National Health and Medical Research Council
Funding Amount
$306,562.00
Summary
Apoptosis is a form of cell suicide that is vital in human development and health by removing damaged or unwanted cells in a regulated manner. Disturbances in this pathway are known to be the cause of cancers and other diseases. This research will investigate how the pivotal step in cell death, termed mitochondrial outer membrane permeabilisation (MOMP) is regulated.
Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.
Extending Life After Lung Transplantation – Defining The Structural And Immunological Drivers Of Chronic Lung Allograft Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$739,190.00
Summary
Lung Transplantation (LTx) saves life. However, chronic rejection limits survival after LTx compared to other solid organ transplants. Chronic rejection develops when the LTx recipient produces antibodies against the donor lung. With a team of global leaders in the field we will dissect the antibody response to LTx. By better understanding the immune drivers of antibody-mediated rejection, we aim to reduce the incidence of chronic rejection thereby improving survival after LTx.