Macromolecular Structure Laboratory

Lab head: Brett Hambly
Location: Blackburn Building, Camperdown

The research programme in this laboratory has two strands:

  1. Determination of the molecular structure and function of proteins, focusing primarily on contractile proteins. Dynamic structural changes within proteins are investigated using the spectroscopic techniques of fluorescence, circular dichroic and electron paramagnetic resonance (EPR) spectroscopy. This laboratory collaborates on projects to determine the structure of proteins at atomic resolution using both X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy. Molecular biology techniques are used to genetically engineer and express muscle proteins we are interested in, to enable new spectroscopic probe sites to be incorporated into relevant proteins and to facilitate NMR and crystallographic studies.
  2. Understanding cardiovascular disease at a molecular and cellular level. Protein biochemical and structural techniques are applied to understanding the protein defects that occur in disease processes such as familial hypertrophic cardiomyopathy and cardiac ischaemia. Additionally, this laboratory has developed tissue culture and other experimental models of atherosclerosis, which are used to examine molecular and cellular changes during atherosgensis. Commercial applications of our discoveries in cardiac ischaemia and atherosclerosis are being exploited.

Lab members: B Hambly (head)

Pathogenesis of Marfan Syndrome and related thoracic aortic aneurysm disease

Primary supervisor: Brett Hambly

Marfan Syndrome is the commonest example of thoracic aortic aneurysm disease (TAAD). These diseases cause dilatation of the thoracic part of the aorta, often resulting in rupture and death during young adult life. Many patients with Marfan Syndrome have mutations in the gene coding for fibrillin, an extra-cellular structural protein that also sequesters TGF-ß. Other mutations occur in the TGF-b receptor. Thus, Marfan appears to be a disease of abnormal TGF-b signalling. Our current studies are focused on profiling the release of biomarkers of aortic damage in the blood, to help us better understand the pathogenesis of TAAD and to help us more accurately diagnose and monitor the progression of TAAD.

This project would involve the detection of biomarkers for TAAD in patient blood samples using a range of protein and genetic assays.

Discipline: Pathology
Co-supervisors: Richmond Jeremy
Keywords: Cardiovascular diseases, Biological markers, Marfan Syndrome