Contacts

Heath Ecroyd 2011

Associate Professor Heath Ecroyd

PhD School of Environmental and Life Sciences, University of Newcastle

Email:    heath_ecroyd@uow.edu.au
Phone:  +61 2 4221 3443
Room:    B32.308

OrcID:    http://orcid.org/0000-0001-7574-0044

 

Research Interests
  • The cellular heat shock response and molecular chaperones
  • 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?
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 

J.J. Yerbury, L. Ooi, A. Dillin, D.N. Saunders, D.M. Hatters, P.M. Beart, N.R. Cashman, M.R. Wilson and H. Ecroyd (2016) Walking the tightrope: Proteostasis and neurodegenerative disease. J Neurochem. doi: 10.1111/jnc.13575.

B. Jovcevski, M.A. Kelly, A.P. Rote, T. Berg, H.Y. Gastall, J.L.P. Benesch, J.A. Aquilina and H. Ecroyd (2015) Phosphomimics destabilise Hsp27 oligomeric assemblies and enhance chaperone activity. Chem Biol. 22, 186-195.

T.M. Treweek, S. Meehan, H. Ecroyd† and J.A. Carver† (2014) Small heat-shock proteins: important players in regulating cellular proteostasis. Cell Mol Life Sci. 72, 429-451.
† - corresponding authors.

D. Cox, J.A. Carver and H. Ecroyd (2014) Preventing alpha-synuclein aggregation: The role of the small heat-shock molecular chaperone proteins. BBA – Mol Basis Dis. 1842, 1830-1843.

 G.K.A. Hochberg†, H. Ecroyd†, C. Liu, D. Cox, D. Cascio, M.R. Sawaya, M.P. Collier, J. Stroud, J.A. Carver, A.J. Baldwin, C.V. Robinson, D.S. Eisenberg, J.L.P. Benesch and A. Laganowsky (2014) The structured core domain of alphaB-crystallin can prevent amyloid fibrillation and associated toxicity. Proc Nat Acad Sci USA. 111, E1562-E1570.
† - these two authors contributed equally to this work.

K.J. Binger†, H. Ecroyd†, S. Yang, J.A. Carver, G.J. Howlett and M.D. Griffin (2013) Avoiding the oligomeric state: AlphaB-crystallin inhibits fragmentation and induces dissociation of apolipoprotein C-II amyloid fibrils. FASEB J. 27, 1214-1222.
† - these two authors contributed equally to this work.

J.A. Aquilina, S, Shrestha, A.M. Morris and H. Ecroyd (2013) Structural and functional aspects of hetero-oligomers formed by small heat shock proteins alphaB-crystallin and Hsp27. J Biol Chem. 288, 13602-13609.

J.J. Yerbury, D. Gower, L. Vanags, K. Roberts, J.A. Lee and H. Ecroyd (2013) The small heat shock proteins alphaB-crystallin and Hsp27 suppress SOD1 aggregation in vitro. Cell Stress Chaperon. 18, 251-257.

A.R. Wyatt, J.J. Yerbury, H. Ecroyd and M.R. Wilson (2013) Extracellular chaperones and proteostasis. Annu Rev Biochem. 82, 295-322.

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-determining 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.

Searchable publications

Current Students

PhD projects

  • Dezerae Cox – The role of small heat shock proteins in diseases associated with alpha-synuclein aggregation.
  • 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).
  • Manjeet Kumar – Understanding the mechanism of action of alpha-synuclein as a molecular chaperone and its role in Parkinson’s disease (based at ANU, co-supervised with Prof John Carver).
  • Anthea Rote – The structure and chaperone function of mutant forms of Hsp27 associated with disease.
  • Rebecca San Gil – Examining the heat shock response in neurons.
  • Caitlin Johnston – Using single molecule techniques to study how chaperone proteins prevent protein misfolding and aggregation (co-supervised with Professor Antione van Oijen).

Honours projects

  • Shannon McMahon – Establishing the role of proteostasis pathways in preventing protein aggregation in cells.
  • Nicholas Marzano – Developing a folding sensor to study chaperone protein function by single molecule fluorescence techniques (co-supervised with Professor Antione van Oijen).

Past Students

  • Lemay Thai – Investigating mutant forms of the small heat shock protein Hsp27 that are associated with disease.
  • Amelia Hall – Establishing alpha-lactalbumin as a model protein to study protein aggregation and its toxic effects.
  • Melissa Kulig - Delineating the chaperone mechanism 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).
  • Laura Vanags – The role of small heat shock proteins in the familial form of Amyotrophic Lateral Sclerosis associated with superoxide dismutase aggregation.
  • Rachel Webb – Small heat shock proteins: an important defence against the onset and progression of amyloid fibril formation in neurodegenerative diseases. 
Suggested Topics for Future Students
  • The cellular heat shock response and chaperone proteins.
  • Proteostasis and ageing.
  • Exploring the role of phosphorylation in regulating the chaperone activity of heat shock proteins.
  • Investigating the mechanism by which proteins aggregate using alpha-lactalbumin as a model protein.
  • Heat shock proteins in Amyotrophic Lateral Sclerosis.
  • Identifying novel inhibitors of protein aggregation the cytotoxicity associated with this process.
Abbreviated CV
  • 2012-Present ARC Future Fellow, School of Biological Sciences, University of Wollongong
  • 2013-Present Assoc Professor, School of Biological Sciences, University of Wollongong 
  • 2011-2012 Senior Lecturer, School of Biological Sciences, University of Wollongong
  • 2009-2010 Lecturer, School of Biological Sciences, University of Wollongong
  • 2005-2009 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
Last reviewed: 5 April, 2016