About Associate Professor Margaret Sunde

Margie's work aims to understand how natural function and complexity in protein self-assembly is corrupted in disease states.

Margie Sunde is an internationally recognized researcher in the field of amyloid structure and protein misfolding.

Before the 1990’s, the deposition of insoluble protein aggregates had been noted in many diseases, including Alzheimer’s, prion diseases and type II diabetes but the underlying mechanism of amyloid formation was unknown. Margie was one of the pioneers in understanding the molecular basis for amyloidosis. She carried out some of the first X-ray fibre diffraction and electron microscopy studies to examine the molecular structure of amyloid fibrils and was able to demonstrate for the first time that all amyloid fibrils, regardless of the nature of the component protein or disease involved, have the same core beta-sheet structure. Margie additionally solved the three-dimensional structures of two amyloidogenic human lysozyme variants and carried out other biophysical studies on these proteins that investigated the molecular basis for their transformation into insoluble aggregates. This work was published in Nature and had a large impact on the field because it was the first demonstration that protein misfolding underlies amyloid formation.
Margie’s work has also shown that normally non-amyloidogenic proteins can be induced to form fibrils under conditions that destabilize the native structure and that natively unstructured proteins can also form amyloid fibrils. These studies have led to the understanding that amyloid formation is a fundamental property of protein chains, not only a disease-associated phenomenon. In recent years, Margie has turned to the study of natural, functional amyloids that are found in many micro-organisms, with a view to understanding the way in which protein self-assembly happens in non-pathogenic states. For example, the group is studying hydrophobins, which are highly surface-active fungal proteins that self-assemble in an ordered manner into amphipathic films at interfaces. Hydrophobin assemblies share many structural similarities with amyloid fibrils but in addition, they display a functional surface.

Selected publications

  • Kwan, A. H., Winefield, R. D., Sunde, M., Matthews, J. M., Haverkamp, R. G., Templeton, M. D.and Mackay, J. P. (2006) Structural basis for rodlet assembly in fungal hydrophobins. Proc. Natl. Acad. Sci. U S A 103, 3621-6. PubMedId: 16537446
  • Marianayagam, N. J., Sunde, M., and Matthews, J. M. (2004) The power of two: protein dimerization in biology. Trends Biochem. Sci. 29, 618-625. PubMedId: 15501681
  • Sunde, M., McGrath, K. C., Young, L., Matthews, J. M., Chua, E. L., Mackay, J. P., and Death, A. K. (2004) TC-1 is a novel tumorigenic and natively disordered protein associated with thyroid cancer. Cancer Research 64, 2766-2773. PubMedId: 15087392
  • Serpell, L. C., Fraser, P. E., and Sunde, M. (1999) X-ray fiber diffraction of amyloid fibrils. Methods Enzymol. 309, 526-536. PubMedId: 10507046
  • Guijarro, J. I., Sunde, M., Jones, J. A., Campbell, I. D., and Dobson, C. M. (1998) Amyloid fibril formation by an SH3 domain. Proc. Natl. Acad. Sci. U S A 95, 4224-4228. PubMedId: 9539718
  • Sunde, M., and Blake, C. C. (1998) From the globular to the fibrous state: protein structure and structural conversion in amyloid formation.Q. Rev. Biophys. 31, 1-39. PubMedId: 9717197
  • #Booth, D. R., #Sunde, M., Bellotti, V., Robinson, C. V., Hutchinson, W. L., Fraser, P. E., Hawkins, P. N., Dobson, C. M., Radford, S. E., Blake, C. C., and Pepys, M. B. (1997) Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis. Nature 385, 787-793. # Joint 1st authors. PubMedId: 9039909
  • Sunde, M., and Blake, C. (1997) The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 50, 123-159. PubMedId: 9338080
  • Sunde, M., Serpell, L. C., Bartlam, M., Fraser, P. E., Pepys, M. B., and Blake, C. C. (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J. Mol. Biol. 273, 729-739. PubMedId: 9356260
  • Serpell, L. C., Sunde, M., Fraser, P. E., Luther, P. K., Morris, E. P., Sangren, O., Lundgren, E., and Blake, C. C. (1995) Examination of the structure of the transthyretin amyloid fibril by image reconstruction from electron micrographs. J. Mol. Biol. 254, 113-118. PubMedId: 7490736