Dr Anthony Fitzpatrick

Interests

Amyloid is an important class of proteinaceous material because of its close association with protein misfolding disorders such as Alzheimer’s disease and type II diabetes. My research focuses on determining the structure, stability and material properties of amyloid and, more generally, understanding the relationship between protein structure, dynamics and function. The methods I use are largely experimental and include cryo-electron microscopy (cryo-EM), magic angle spinning NMR (MAS NMR), X-ray diffraction (XRD), atomic force microscopy (AFM) and, more recently, time-resolved electron microscopy (4D EM). The articles below provide a detailed description of the current areas of my research.

Atomic Structure of a Family of Amyloid Fibrils
Atomic Structure of a Family of Amyloid Fibrils
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Research Focus

Keywords

Amyloid

Protein aggregation

Protein structure

Protein dynamics

Clinical conditions

Alzheimer's disease

Alzheimer's disease

Huntington's disease

Parkinson's disease

Tauopathies

Equipment

Atomic force microscopy

Computational modelling

Cryo-electron microscopy

Nuclear Magnetic Resonance

Time-resolved electron microscopy (4D EM)

X-ray diffraction

Collaborators

Cambridge

Christopher Dobson

Michel Goedert

Michele Vendruscolo

International

Robert Griffin Web: http://web.mit.edu/chemist...

Associated News Items


    Key publications

    Fitzpatrick, AW, Falcon, B, He, S, Murzin, AG, Murshudov, G, Garringer, HJ, Crowther, RA, Ghetti, B, Goedert, M, Scheres, SHW (in press), “Cryo-EM structures of tau filaments in Alzheimer’s disease ” Nature

    Fitzpatrick AW, Debelouchina GT, Bayro MJ, Clare DK, Caporini MA, Bajaj VS, Jaroniec CP, Wang L, Ladizhansky V, Müller SA, MacPhee CE, Waudby CA, Mott HR, De Simone A, Knowles TP, Saibil HR, Vendruscolo M, Orlova EV, Griffin RG, Dobson CM (2013), “Atomic structure and hierarchical assembly of a cross-β amyloid fibril.” Proc Natl Acad Sci U S A 110(14):5468-73 Details

    Knowles TP, Fitzpatrick AW, Meehan S, Mott HR, Vendruscolo M, Dobson CM, Welland ME (2007), “Role of intermolecular forces in defining material properties of protein nanofibrils.” Science 318(5858):1900-3 Details

    Publications

    2017

    Fitzpatrick, AW, Llabrés, S, Neuberger, A, Blaza, JN, Bai, XC, Okada, U, Murakami, S, van Veen, HW, Zachariae, U, Scheres, SHW, Luisi, BF, Du, D (2017), “Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump” Nature Microbiology 2:17070

    2016

    Vanacore GM, Fitzpatrick AW, Zewail AH (2016), “Four-dimensional electron microscopy: Ultrafast imaging, diffraction and spectroscopy in materials science and biology” Nano Today 11 (2), 228-249

    2015

    Anthony W. P. Fitzpatrick, Giovanni M. Vanacore, and Ahmed H. Zewail (2015), “Nanomechanics and intermolecular forces of amyloid revealed by four-dimensional electron microscopy” Proceedings of the National Academy of Sciences

    2013

    Debelouchina GT, Bayro MJ, Fitzpatrick AW, Ladizhansky V, Colvin MT, Caporini MA, Jaroniec CP, Bajaj VS, Rosay MM, Macphee CE, Vendruscolo M, Maas WE, Dobson CM, Griffin RG (2013), “Higher Order Amyloid Fibril Structure by MAS NMR and DNP Spectroscopy.” J Am Chem Soc Details

    Fitzpatrick AW, Lorenz UJ, Vanacore GM, Zewail AH (2013), “4D cryo-electron microscopy of proteins.” J Am Chem Soc 135(51):19123-6 Details

    Fitzpatrick AW, Park ST, Zewail AH (2013), “Exceptional rigidity and biomechanics of amyloid revealed by 4D electron microscopy.” Proc Natl Acad Sci U S A 110(27):10976-81 Details

    Waudby CA, Camilloni C, Fitzpatrick AW, Cabrita LD, Dobson CM, Vendruscolo M, Christodoulou J (2013), “In-cell NMR characterization of the secondary structure populations of a disordered conformation of α-synuclein within E. coli cells.” PLoS One 8(8):e72286 Details

    2012

    Knowles TP, De Simone A, Fitzpatrick AW, Baldwin A, Meehan S, Rajah L, Vendruscolo M, Welland ME, Dobson CM, Terentjev EM (2012), “Twisting transition between crystalline and fibrillar phases of aggregated peptides.” Phys Rev Lett 109(15):158101 Details

    2011

    Baldwin AJ, Knowles TP, Tartaglia GG, Fitzpatrick AW, Devlin GL, Shammas SL, Waudby CA, Mossuto MF, Meehan S, Gras SL, Christodoulou J, Anthony-Cahill SJ, Barker PD, Vendruscolo M, Dobson CM (2011), “Metastability of native proteins and the phenomenon of amyloid formation.” J Am Chem Soc 133(36):14160-3 Details

    Fitzpatrick AW, Knowles TP, Waudby CA, Vendruscolo M, Dobson CM (2011), “Inversion of the balance between hydrophobic and hydrogen bonding interactions in protein folding and aggregation.” PLoS Comput Biol 7(10):e1002169 Details

    2010

    Caporini MA, Bajaj VS, Veshtort M, Fitzpatrick A, MacPhee CE, Vendruscolo M, Dobson CM, Griffin RG (2010), “Accurate determination of interstrand distances and alignment in amyloid fibrils by magic angle spinning NMR.” J Phys Chem B 114(42):13555-61 Details

    2008

    Strodel B, Fitzpatrick AW, Vendruscolo M, Dobson CM, Wales DJ (2008), “Characterizing the first steps of amyloid formation for the ccbeta peptide.” J Phys Chem B 112(32):9998-10004 Details