Projects

CONTENTS


HUMAN Heart Failure (Cris dos Remedios, Sean Lal, Maurizio Stefani, Soraya Joseph, Claudio Soto, Lisa Nguyen, Rabi Fasouli, Alan Lackey)
Animal models of human heart failure provide valuable clues to understanding human heart failure, but often their mouse physiology is very different from humans. Thus, in the end we have to examine the human heart failure to determine if the information from mouse models is relevant. One the other hand, the study human heart failure is fraught with problems including multiple medications, very mixed genetic background, and major differences in lifestyle between individuals. Such causes of variability make it difficult to assess how much of it is due to the disease. Since 1989 we have moved to solve this problem by collecting a large bank of human heart tissue. We are now in a position to attempt to many key proteins suspected of being related to, indicative of, or actually causative of heart failure, and to compare them with a bank of over 100 non-failing human hearts covering a wide range of ages. We have developed new investigative platforms including antibody microarrays, Tissue MicroArrays (TMAs), as well as techniques to monitor the functional performance of muscle fibers, myofibrils and muscle filaments. Many of our failing heart samples have been and continue to be investigated by collaborators in major research laboratories in the USA (e.g. Harvard, Johns Hopkins U, U. Minnesota), Europe (London, Dublin, Amsterdam, Bochum, Nantes), and Japan (Waseda U, Tokyo Medical and Dental U).

In a related project, we collaborate with Dr Bernhard Kuhn (Children’s Hospital, Harvard Medical School) to examine how human hearts change with age, how they repair, and how they respond to disease.

HUMAN Prostate Cancer (Vicki Velonas, Henry Woo, Steve Assinder)
Prostate cancer is a major cause of mortality in men. Current methods of diagnoses that differentiate between benign and malignant prostate hypertrophy are beset with problems, particularly high false negative rates. We are working with other prostate cancer researchers (Dr Steve Assinder) and clinicians (Dr Henry Woo) to identify novel biomarkers for metastatic prostate cancer. We use antibody microarrays, mass spectrometry and electron microscopy with a particular focus on very small membrane vesicles called exosomes).

Novel Methods for Immobilizing Proteins (Marcela Bilek, David McKenzie, Neil Nosworthy, Stacey Hirsch, Elena Kosbrodova)
We won the 2011 Australian Innovation Award for technology that makes it possible to permanently immobilize biomolecules (proteins, nucleotides) on solid surfaces. We have used this to develop more efficient production of ethanol (starting with plant waste products and using “removable” enzymes that turn cellulose into sugars). Our recent paper in Proceedings of the National Academy of Science (USA) is a good example. We are actively looking for new ways to combine this technology with biomedical applications.

Bioassays for Water Pollution (Cris dos Remedios, Leo Phillips, Vangelis Kanellis)
Clean water is a shrinking global resource, particularly in developing countries. We have developed a novel bioassay using DNA to monitor total biotoxicity in water samples. The technique is quick, portable, inexpensive and quantitative. We are working with other groups on campus to develop tests for specific toxic chemicals that currently present a threat to potable water, particularly in the Murray Irrigation Area.

Molecular basis of human heart failure
In 1989 I began to collaborate with the late Dr Victor Chang, and over the last 18 years I have collaborated with the Heart/Lung Transplant Unit at St Vincent's Hospital, collecting over 14,000 samples from nearly 350 failing human hearts and more than 50 un-used donor (non-failing) hearts.

We share these samples with over 30 research groups in nine countries. We have examined these samples using “gene chips” (Harvard, USA and Nantes, France collaborations), using proteomic analyses (Johns Hopkins University, USA; Free University, Amsterdam; Dublin, Ireland), as well as a number of specialist techniques including molecular motility assays (Imperial College, London), single fibre dynamics (King's College, London), titin analysis (Muenster University, Germany), and Spontaneous Oscillatory Contractions (Tokyo, Japan) to name a few.

We coordinate these independent research projects with our own research projects. Our projects involve transcriptomics, proteomics and specialized projects involving the proteins in the intercalated disc in health and disease.

Detecting cancer metastasis from 5mL of blood
We monitor the surface antigens on white blood cells (leukocytes) looking for markers associated with cancer (particularly melanoma and breast cancer).

The search is done by isolating mononuclear cells (or granulocytes) and applying them to an extensive array of antibody dots. Each antibody is directed against known surface marker proteins that are accessible to the extracellular matrix. When a leukocyte (e.g. T lymphocytes) recognizes a non-self protein attached to a non-self cell, it sets in motion a chain of events that result in the destruction of these cells. If this reaction/identification does not occur or is impaired, there will be no inflammatory response.

Some cancer patients have the ability prevent metastases, thus stopping the metastatic spread of their cancer) while others do not. We are developing tests that can identify these two groups of patients.