Dr Heath Ecroyd

Senior Lecturer
Room: 32.232
Phone: +61 2 4221 3443
heath_ecroyd@uow.edu.au

Research Interests

Proteostasis and the role of the small heat shock family of molecular chaperones in this process.

The structure-function relationship of small heat shock proteins

Protein aggregation and its association with diseases such as Parkinson’s disease.

The mechanism by which proteins aggregate and ways in which it can be prevented.

What is proteostasis?

Maintaining protein homeostasis or proteostasis is important in the normal 'housekeeping' of the body.

The control of protein homeostasis heavily relies on molecular chaperones and protein degradation. However, in reality, there are many processes in place to ensure that proteostasis is maintained. In order to produce a properly functioning protein, the processes of transcription, RNA processing and transport, translation, protein folding, protein transport and ultimately protein degradation must be tightly regulated.

Representative Publications

M.Kulig and H.Ecroyd (2012) The small heat shock protein alphaB-crystallin uses different mechanisms of chaperone action to prevent the amorphous versus fibrillar aggregation of alpha-lactalbumin. Biochem J. 448, 343-352.

S.L. Shammas, C.A. Waudby, S. Wang, A.K. Buell, H. Ecroyd, M.E. Welland, J.A. Carver, C.M. Dobson and S. Meehan (2011) Binding of the molecular chaperone alphaB-crystallin to amyloid-beta amyloid fibrils inhibits their elongation. Biophys J. 101, 1681-1689.

D.M. Williams, H. Ecroyd, K.L. Goodwin, H. Dai, H. Fu, J.M. Woodcock, L. Zhang and J.A. Carver (2011) NMR spectroscopy of 14-3-3zeta reveals a flexible C-terminal extension. Differentiation of the chaperone and phosphoserine binding activities of 14-3-3zeta. Biochem J. 437, 493-503.

A.L. Robertson, S.J. Headey, H.M. Saunders, H. Ecroyd, M.J. Scanlon, J.A. Carver and S.P. Bottomley (2010) Small heat shock proteins inhibit polyglutamine aggregation by interactions with a flanking domain. Proc Nat Acad Sci USA. 107, 10424-10429.

H. Ecroyd, D.C. Thorn, Y. Liu and J.A. Carver (2010) The dissociated form of kappa-casein is the precursor to its amyloid fibril formation. Biochem J. 429, 251-260.

S.D. Stranks, H. Ecroyd, S. van Sluyter, E.J. Waters, J.A. Carver and L. von Smekal (2009) Model for amorphous aggregation processes. Phys Rev E. 80, 051907.

H. Ecroyd, and J. A. Carver. (2009) Crystallin proteins and amyloid fibrils. Cell Mol Life Sci. 66, 62-81.

H. Ecroyd, and J. A. Carver. (2008) Unravelling the mysteries of protein folding and misfolding. IUBMB Life. 60, 769-774.

H. Ecroyd, T. Koudelka, D.C. Thorn, G. Devlin, D. Williams, P. Hoffmann and J.A. Carver. (2008) Dissociation from the oligomeric state is the rate-determing step in amyloid fibril formation by kappa-casein. J Biol Chem 283, 9012-9022.

H. Ecroyd and J.A. Carver. (2008) The effect of small molecules on the chaperone activity of alphaB-crystallin against ordered and disordered forms of aggregation. FEBS J. 275, 935-947.

D.C. Thorn, H. Ecroyd, M. Sunde, S. Poon and J.A. Carver. (2008) Amyloid fibril formation by bovine milk alphaS2-casein occurs under physiological conditions yet is prevented by its natural counterpart, alphaS1-casein. Biochemistry 47, 3926-3936.

H. Ecroyd, S. Meehan, J. Horwitz, J.A. Aqulina, J.L. Benesch, C.V. Robinson, C.E. MacPhee and J.A. Carver. (2007) Mimicking phosphorylation of alphaB-crystallin affects its chaperone activity. Biochem J. 401, 129-141.

T. M. Treweek, H. Ecroyd, D.M. Williams, S. Meehan, J.A. Carver and M.J. Walker. (2007) Site-directed mutations in the C-Terminal extension of human alphaB-crystallin affect chaperone function and block amyloid fibril formation. PLoS ONE. 17: e1046.

Current Students

PhD Students

Dezera Cox - The role of small heat shock proteins in diseases associated with alpha-synuclein aggregation

Honours Projects

Anthea Rote – Using phosphomimics of Hsp27 to examine the effect of phosphorylation on its structure and function

Rebecca San Gil – The effect of phosphorylation on the structure and function of the small heat shock protein alphaB-crystallin

Past Students

Amelia Hall – Establishing alpha-lactalbumin as a model protein to study protein aggregation and its toxic effects.

Melissa Kulig - Delineating the chaperone binding sites of small heat shock proteins.

Erin Temby - The role of small heat shock proteins in amyloid fibril formation associated with Parkinson’s disease.

Dane Gower – small heat shock proteins and Amyotrophic Lateral Sclerosis. (Co-supervised with Dr Justin Yerbury)

Sudichhya Shrestha – Hetero-oligomeric complexes of Hsp27 and alphaB-crystallin: Structural and functional aspects. (Co-supervised with Dr Andrew Aquilina)

Blagojce Jovcevski – Using mass spectrometry to investigate the complexes formed between the small heat shock proteins Hsp20, Hsp27 and alphaB-crystallin. (Co-supervised with Dr Andrew Aquilina)

Suggested Topics for Future Students

Investigating the role of phosphorylation in regulating the chaperone activity of small heat shock proteins

Investigating the mechanism by which proteins aggregate using alpha-lactalbumin as a model protein

Small heat shock proteins in Amyotrophic Lateral Sclerosis.

Identifying novel inhibitors of amyloid fibril formation and the cytotoxicity associated with this process

Abbreviated CV

2012-Present  ARC Future Fellow, School of Biological Sciences, University of Wollongong

2011-Present Senior Lecturer, School of Biological Sciences, University of Wollongong

2009-2010       Lecturer, School of Biological Sciences, University of Wollongong

2009-2010       Adjunct Lecturer, School of Chemistry and Physics, University of Adelaide

2005-2008       NHMRC Peter Doherty Fellow, School of Chemistry and Physics, University of Adelaide

2003-2004       Post-doctoral Fellow, Institut National de la Recherche Agronomique (INRA), Tours-Nouzilly, France

2000-2003      PhD, School of Environmental and Life Sciences, University of Newcastle