ProfessorPaul Witting

Project Opportunities

Title: Assessing changes to myocardial proteins subsequent to experimental heart attack

Summary of opportunity:

Post translational changes to key cardiac proteins in the hearts of diabetic rats after experimental heart attack

Opportunity synopsis:

The major causes of morbidity and mortality in diabetes are the cardiovascular complications of the disease. Of these, the development of diabetic cardiomyopathy is of particular concern, as it increases the risk and severity of acute myocardial infarction (heart attack) compared with the general population. The proposed project will provide information on the role for oxidative stress and inflammation in promoting the severity of myocardial infarct in an animal model of diabetic cardiomyopathy. We plan to use an established rat model of diabetes and monitor post translational changes to key cardiac proteins through a proteomic approach combining 2D gel and mass spectrometry peptide mass mapping. An understanding of the role for oxidative stress and inflammation following acute myocardial infarct in diabetics may allow the development of new therapeutic approaches targeted at slowing down the progression of cardiomyopathy and thereby potentially improving heart function and quality of life in diabetes sufferers. This would be viewed as a major advance. The researcher will use the tools of proteomics to investigate markers of heart disease and the post-translational modification of proteins resulting from cardiovascular disease in the setting of diabetes. We have established an animal model of diabetic cardiomyopathy and will use this model to assess changes in key cardiac proteins resulting from experimental heart attack. Specific techniques include liquid chromatography, 1D and 2D electrophoresis, mass spectrometry coupled with peptide mass mapping.

Project Opportunities

Title: Impact of chronic inflammation on bowel and sexual function

Summary of opportunity:

Inflammatory bowel diseases (IBD) is difficult to treat and secondary pathological outcome can include decreased fertility. Also, many of the available treatments cause unwanted severe immune side effects that limit their therapeutic benefit. Therefore, the development of innovative therapies that target inflammation in the bowel is warranted and may have secondary benefial impacts on fertility in males and females.

Opportunity synopsis:

Inflammatory bowel diseases (IBD; Crohn's disease; ulcerative colitis) are a group of inflammatory disorders of gastrointestinal tract with unknown etiology. Australian IBD patients tend to retire early and A$3.1 billion productive loss has been attributed to IBD with an estimate of ~ 100,000 new cases to be reported by 2022. IBD is also a threat to patient's fertility potential and in Australia, voluntary childlessness is high in IBD patients with the fear of its heritability and possible medicinal effects on the child. IBD impacts the fertility status of either genders directly (disease itself) by oxidative stress or indirectly (immunosuppressive treatment; surgical/non-surgical). Establishing an innovative, non-immunological therapy will alleviate the inflammatory course of IBD and thus minimize our dependency on immunosuppressant drugs, that exhibit severe and noxious side-effects. In this context we propose to investigate whether nitroxides as a novel class of potent anti-inflammatory/antioxidant agents ameliorate IBD in a severe combined immune-deficient mouse (SCID) model that closely recapitulates human IBD.

----------Current Research Projects----------

We have projects avaialble that focus on micronytirents in health (selenium) and the development of innovative therapeutics that target inflammatory disorders fo the bowel and heart.