Cardiac Nanobiology Group

  

  

Principal Investigator


Research Interest

Confocal cardio
Confocal micrograph of healthy human cardiac myocytes labelled with Wheat Germ Agglutinin.

What is nanobiology? Put simply it is the study of biological interactions at the nanoscale. In the Cardiac Nanobiology Lab we study the macro-molecular complexes that regulate cardiac muscle cell Ca2+ release and how nanoscale remodelling of these complexes contribute to the loss of contractility in the failing human heart.

This research encompasses length scales from molecules, to organelles, to cells, to tissue and whole organ. Of particular interest is the pathological remodelling of the transverse (t)-tubules that occurs in the failing heart. T-tubules are tube like extensions of the plasma membrane (~300 nm in dia) that penetrate deep within ventricular myocytes that facilitate a rapid conduction of the action potential into the centre of the cell where they help synchronise cell-wide Ca2+ release that controls contraction.

We have recently identified that there is increased collagen within the dilated t-tubules in human heart failure. This research was featured on the cover of Cardiovascular Research (Crossman et al 2017) and the accompanying editorial stated “…their work raises the exciting hypothesis that collagen deposition within t-tubules drives their structural remodelling.” (DOI: 10.1093/cvr/cvx091)

We have recently been funded to explore the role of collagen in t-tubule remodelling in the Health Research Council of New Zealand, 2018 Project “Nanoscale fibrosis and loss of contractility in the failing human heart” https://www.hrc.govt.nz/resources/research-repository/nanoscale-fibrosis-and-loss-contractility-failing-human-heart.

 

Super resolution
Super-resolution microscopy identifies increased type VI collagen within the lumen of t-tubules in the failing human heart.

Super-Resolution Microscopy

Nanobiology has been revolutionised by the development of super-resolution microscopes that break the diffraction barrier (~250 nm) and allow visualisation of high contrast molecularly specific fluorescent probes in cells and tissue at a resolution of tens of nanometres. Within the laboratory we have a custom built dSTORM microscope and analysis software developed by Dr David Baddeley (http://python-microscopy.org/). dSTORM is a form of localisation microscopy which relies on photo-chemistry to switch fluorescence molecules on and off. By using a laser and a specialised buffer, individual molecules can be imaged one at a time.

These appear as diffraction limited spot (~250 nm in dia). Image analysis software then finds the precise centre of each individual molecule at accuracy ~20 fold better than the diffraction limited width. From tens of thousands or more of these precise localisations a high resolution image is produced.

 

    

Research Projects

There are opportunities for student research including PhD, Masters, Honours and Summer projects. If this is of interest please get in contact.

 

Grant funding

We are grateful to have received funding from the following funding agencies:

  • Health Research Council of New Zealand
  • Auckland Medical Research Foundation
  • Marsden Fund
  • Lotteries Health Research
  • Green Lane Research and Educational Fund 
  • Maurice and Phyllis Paykel Trust

 

Selected Research publications


  • Crossman DJ, Shen X, Jüllig M, Munro M, Hou Y, Middleditch M, Shrestha D, Li A, Lal S, dos Remedios CG, Baddeley D, Ruygrok PN, Soeller C (2017) Increased collagen within the transverse tubules in human heart failure. Cardiovascular Research.113: 879-891.
  • Crossman DJ, Hou Y, Jayasinghe I, Baddeley D, and Soeller C. (2015). Combining confocal and single molecule localisation microscopy: a correlative approach to multi-scale tissue imaging. Methods.80:98-108.
  • Crossman DJ, Young AA, Ruygrok PN, Nason GP, Baddelely D, Soeller C, Cannell MB. (2015) t-tubule disease: Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy. Journal of Molecular and Cellular Cardiology. 84:170–178.
  • Baddeley D, Crossman D, Rossberger S, Cheyne JE, Montgomery JM, Jayasinghe ID, Cremer C, Cannell MB, Soeller C. (2011) 4D super-resolution microscopy with conventional fluorophores and single wavelength excitation in optically thick cells and tissues. PLoS one. 6(5):e20645.
  • Crossman DJ, Ruygrok PR, Soeller C, Cannell MB. (2011) Changes in the organization of excitation-contraction coupling structures in failing human heart. PLoS one. 6(3):e1901.

 

Cardiovascular research