Hatters Laboratory: Protein Misfolding and Proteostasis in Neurodegenerative Diseases

Overview

Research in the Hatters lab is focused on understanding the molecular mechanisms underpinning neurodegenerative diseases involving protein mis-folding and aggregation.  This primarily includes Huntington’s and Motor Neuron Diseases.  Our efforts involve building new biosensors and methods to track the misfolded and aggregated states of proteins in cells and using these approaches to determine how they interact with the cellular machinery to propagate dysfunction or trigger adaptive responses to stress.  Other related areas of research include defining the latent efficiency of cells to manage folding of the proteome, and the molecular biology of stress granule formation.

Staff

Ms Angelique Ormsby, RA
Ms Yasmin Ramdzan, RA
Ms Rebecca Wood, RA
Ms Autumn Bricker, PhD Student
Mr Nagaraj Moily, PhD Student
Ms Estella Newcombe, PhD Student
Ms Mona Radwan, PhD Student
Ms Xiaojing Sui, PhD Student
Mr Mikhail Trubetskov, PhD Student
Mr Andrew Ngo, Masters Student

Collaborators

A/Prof Alicia Oshlack, Murdoch Children’s Research Institute
A/Prof Paul Gooley, Department of Biochemistry and Molecular Biology, The University of Melbourne
Dr Yuning Hong, School of Chemistry, The University of Melbourne
Prof Paul Gleeson, Department of Biochemistry and Molecular Biology, The University of Melbourne
Dr Till Böcking, University of New South Wales
A/Prof Alex Dickson, Michigan State University
Dr Justin Yerbury, University of Wollongong
Dr Simon Ebbinghaus, Ruhr University Bochum.
Prof Anthony Hannan, Florey Neurosciences Institute, The University of Melbourne
Prof Gavin Reid, Department of Biochemistry and Molecular Biology, The University of Melbourne

Funding

ARC Future Fellowship: ‘Defining the cellular impacts of protein aggregation in neurodegenerative disease with an aggreomics platform'
NHMRC Project Grant: ‘Pathogenic and adaptive molecular interactions with mutant huntingtin exon 1'
NHMRC Project Grant: ‘Spatial organization of Lck as a regulatory mechanism of TCR signalling’

Research Publications

Click here for the results of a PubMed search of Danny's publications.

Click here for the results of a Google Scholar analysis of Danny's publications.

  1. Polling S, Ormsby AR, Wood RJ, Lee K, Shoubridge C, Hughes JN, Thomas PQ, Griffin MD, Hill AF, Bowden Q, Bocking T, Hatters DM.  Polyalanine expansions drive a shift into alpha-helical clusters without amyloid-fibril formation. Nat Struc Mol Biol 2015: 22: 1008-1015.
  2. Zeineddine R, Pundavela JF, Corcoran L, Stewart EM, Do-Ha D, Bax M, Guillemin G, Vine KL, Hatters DM, Ecroyd H, Dobson CM, Turner BJ, Ooi L, Wilson MR, Cashman NR, Yerbury JJ.  SOD1 protein aggregates stimulate macropinocytosis in neurons to facilitate their propagation. Mol Neurodegener 2015; 10: 57.
  3. Hennig S, Kong G, Mannen T, Sadowska A, Kobelke S, Blythe A, Knott GJ, Iyer KS, Ho D, Newcombe EA, Hosoki K, Goshima N, Kawaguchi T, Hatters D, Trinkle-Mulcahy L, Hirose T, Bond CS, Fox AH.  Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. J Cell Biol 2015; 210: 529-539.
  4. Farrawell NE, Lambert-Smith IA, Warraich ST, Blair IP, Saunders DN, Hatters DM, Yerbury JJ.  Distinct partitioning of ALS associated TDP-43, FUS and SOD1 mutants into cellular inclusions. Sci Rep 2015; 5: 13416.
  5. Polling S, Mok YF, Ramdzan YM, Turner BJ, Yerbury JJ, Hill AF, Hatters DM. Misfolded polyglutamine, polyalanine, and superoxide dismutase 1 aggregate via distinct pathways in the cell. J Biol Chem 2014; 289: 6669-6680.
  6. Irtegun S, Wood R, Lackovic K, Schweiggert J, Ramdzan YM, Huang DC, Mulhern TD, Hatters DM.  A biosensor of SRC family kinase conformation by exposable tetracysteine useful for cell-based screening. ACS Chem Biol 2014; 9: 1426-1431.
  7. Chia PZ, Ramdzan YM, Houghton FJ, Hatters DM, Gleeson PA.  High-throughput quantitation of intracellular trafficking and organelle disruption by flow cytometry. Traffic 2014;15: 572-582.
  8. Ormsby AR, Ramdzan YM, Mok YF, Jovanoski KD, Hatters DM.  A platform to view huntingtin exon 1 aggregation flux in the cell reveals divergent influences from chaperones hsp40 and hsp70. J Biol Chem 2013;288: 37192-37203.
  9. Ramdzan YM, Polling S, Chia CP, Ng IH, Ormsby AR, Croft NP, Purcell AW, Bogoyevitch MA, Ng DC, Gleeson PA, Hatters DM.  Tracking protein aggregation and mislocalization in cells with flow cytometry. Nat Methods 2012; 9: 467-470.
  10. Hatters DM. Putting huntingtin "aggregation" in view with windows into the cellular milieu. Curr Top Med Chem 2012;12: 2611-2622.