Student research project
Supervisor(s): Dr Bianca Bernardo and Associate Professor Julie McMullen
Project summary
This project is to understand and target a key anti-fibrotic pathway called the bone morphogenetic protein (BMP) pathway. Targeting the BMP axis is of particular interest in the heart for a number of reasons:
- The BMP pathway is a potent inhibitor of fibrosis in the kidney and liver.
- Previous work involving A/Prof McMullen demonstrated recombinant (rh) BMP7 has therapeutic potential in the heart, however, the cost of ongoing administration of rh-BMP7 protein to heart failure patients hinders its progression to the clinic.
- Dr Bernardo has preliminary data showing that BMP signalling is impaired in heart disease mouse models.
- A small molecule called tilorone has been identified as a drug that can restore BMP7 signalling and is cheap to manufacture.
- We have pilot data demonstrating proof of concept that tilorone can activate BMP signalling in cardiomyocytes and attenuate fibrosis in a mouse model of cardiac injury.
- It is of clinical relevance, in collaboration with Professor David Kaye, we have data to show that tilorone can attenuate transforming growth factor β (TGFβ) stimulated collagen synthesis in human patient fibroblasts.
The main goal of this study is to determine the mode of action of tilorone in cultured fibroblasts.
Related methods, skills or technologies
The project is suitable for an Honours or PhD student and will involve applying various skills and techniques, including:
- preclinical procedures (echocardiography, dissection, i.p. injections)
- qPCR
- Western blot
- cell culture / luciferase assays
- molecular cloning
- histological techniques to measure fibrosis, cell size, angiogenesis and apoptosis.