skip to content
 

Professor Christopher Dobson FRS FMedSci

Our research interests are primarily focused on the investigation of the structures and properties of biological molecules, especially proteins, and their relationship to biological evolution and disease. We have particular interest in the fundamental science underlying disorders such as Alzheimer's and Parkinson's disease. In addition, however, we have recently become involved in the novel utilisation of biological molecules in materials science and nanotechnology.

The methods we use are largely experimental, but do include theoretical and computational approaches. Much of the work is highly interdisciplinary, and people joining the group come from a wide variety of scientific backgrounds ranging from experimental biochemistry to theoretical physics. The research group is based in the Chemistry Department in a newly constructed laboratory located in the Unilever Building. The range of experimental techniques used by the group is very large, including NMR, EM, AFM and X-ray diffraction, as well as a variety of methods based on optical spectroscopy, including fluorescence and circular dichroism. Many, but not all, members of the group also use the techniques of protein chemistry and molecular biology.

The group has close links with scientists in other laboratories in Cambridge, including the Clinical School, the Genetics Department and the Nanoscience Centre and, indeed, some members of the group have been largely based in these departments. New members of the group usually develop a project by discussion with me, along with other members of the research team. Group members are often involved in joint projects with other laboratories and may spend periods of time working with our collaborators in other parts of the world.

More information: Chris Dobson full CV (Microsoft Word)(PDF);Chris Dobson Publications list(Microsoft Word)(PDF).

The following articles provide a general appreciation of our current areas of research:

Reviews

F. Chiti and C.M. Dobson, "Protein misfolding, amyloid formation, and human disease: a summary of progress over the last decade" Annu Rev Biochem, 86, 27-68 (2017).

N. Cremades, S.W. Chen and C.M. Dobson, "Structural characteristics of α-synuclein oligomers" Int Rev Cell Mol Biol, 329, 79-143 (2017).

T.P.J. Knowles, M. Vendruscolo and C.M. Dobson, "The physical basis of protein misfolding disorders" Physics Today, 68, 36-41 (2015).

T.P.J. Knowles, M. Vendruscolo and C.M. Dobson. “The Amyloid State and its Association with Protein Misfolding Diseases”, Nature Rev Mol Cell Biol, 15, 384-396 (2014).  

E.P. O’Brien, P. Ciryam, M. Vendruscolo and C.M. Dobson, “Understanding the influence of codon translation rates on cotranslational protein folding” Acc Chem Res, 47, 1536-44 (2014).

S.I. Cohen, M. Vendruscolo, C.M. Dobson and T.P. Knowles, "From macroscopic measurements to microscopic mechanisms of protein aggregation" J Mol Biol, 41, 160-171 (2012).

L.D. Cabrita, C.M. Dobson, and J. Christodoulou, "Protein folding on the ribosome" Curr Opin Struct Biol,  20, 33-45 (2010).

F. Chiti and C.M. Dobson, Amyloid Formation by Globular Proteins under Native Conditions, Nature Chem Biol, 5, 15-22 (2009)

L.M. Luheshi, D.C. Crowther and C.M. Dobson, Protein Misfolding and Disease: From the Test Tube to the Organism, Curr Opin Chem Biol, 12, 25-31 (2008)

M. Vendruscolo and C.M. Dobson, Dynamic Visions of Enzymatic Reactions, Science, 313, 1586- 1587 (2006)

F. Chiti and C.M. Dobson, Protein Misfolding, Functional Amyloid and Human Disease, Annu Rev Biochem, 75, 333-366 (2006)

C.M. Dobson, Chemical Space and Biology, Nature, 432, 824-882 (2004)

C.M. Dobson, Protein Folding and Misfolding, Nature, 426, 884-890 (2003)

C.M. Dobson, Protein Misfolding, Evolution and Disease, Trends Biochem Sci, 24, 329-332 (1999)

C.M. Dobson, A. Sali and M. Karplus, Protein Folding: A Perspective from Theory and Experiment, Angew Chem Int Ed Eng, 37, 868-893 (1998)

Selected Publications

G. Fusco, S.W. Chen, P.T.F. Williamson, R. Cascella, M. Perni, J.A. Jarvis, C. Cecchi, M. Vendruscolo, F. Chiti, N. Cremades, L. Ying, C.M. Dobson and A. De Simone, "Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers" Science, 358, 1440-1443 (2017).

R. Kundra, P. Ciryam, R.I. Morimoto, C.M. Dobson CM and Vendruscolo M, "Protein homeostasis of a metastable subproteome associated with Alzheimer's disease" Proc Natl Acad Sci USA, 114, E5703-E5711 (2017).

J. Habchi, P. Arosio, M. Perni, A.R. Costa, M. Yagi-Utsumi, P. Joshi, S. Chia, S.I. Cohen, M.B. Müller, S. Linse, E.A. Nollen, C.M. Dobson, T.P.J. Knowles and M. Vendruscolo, "An anticancer drug suppresses the primary nucleation reaction that initiates the production of the toxic Aβ42 aggregates linked with Alzheimer's disease" Sci Adv, 2, e1501244 (2016).

L.D. Cabrita, A.M. Cassaignau, H.M. Launay, C.A. Waudby, T. Wlodarski, C. Camilloni, M.E. Karyadi, A.L. Robertson, X. Wang, A.S. Wentink, L.S. Goodsell, C.A. Woolhead, M. Vendruscolo, C.M. Dobson and J. Christodoulou, "A structural ensemble of a ribosome-nascent chain complex during cotranslational protein folding" Nat Struct Mol Biol, 23, 278-85 (2016).

S.I. Cohen, P. Arosio, J. Presto, F.R. Kurudenkandy, H. Biverstål, L. Dolfe, C. Dunning, X. Yang, B. Frohm, M. Vendruscolo, J. Johansson, C.M. Dobson, A. Fisahn, T.P.J. Knowles and S. Linse, "A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers" Nat Struct Mol Biol, 22, 207-213 (2015).

C. Galvagnion, A.K. Buell, G. Meisl,T.C. Michales, M. Vendruscolo, T.P.J. Knowles and C.M. Dobson, "Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation" Nat Chem Biol, 11, 229-234 (2015).

A.W. Fitzpatrick, G.T. Debelouchina, M.J. Bayro, D.K. Clare, M.A. Caparoni, V.S. Bajaj, C.P. Jaroniec, L. Wang, V. Ladizhansky, S.A. Muller, C.E. MacPhee, C.A. Waudby, H. Mott, A. de Simone, T.P.J. Knowles, H.R. Saibil, M. Vendruscolo, E. Orlova, R.G.Griffin and C.M. Dobson, “Atomic-resolution Structure of a Cross-b  Amyloid Fibril”, Proc Natl Acad Sci USA, 110, 5468-5473 (2013).

S.I. Cohen, S. Linse, L.M. Luheshi, E. Hellstrand, D.A. White, L. Rajah, D.E. Otzen, M. Vendruscolo, C.M. Dobson and T.P. Knowles, "Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism", Proc Natl Acad Sci USA 110, 9758-9763 (2013).

N. Cremades, S.I. Cohen, E. Deas, A.Y. Abramov, A.Y. Chen, A. Orte, M. Sandal, R.W. Clarke, P. Dunne, F.A. Aprile, C.W. Bertoncini, N.W. Wood, T.P. Knowles, C.M. Dobson and D. Klenerman. "Direct Observation of the Interconversion of Normal and Toxic Forms of α- Synuclein", Cell 149, 1048-1059 (2012).

A. De Simone, A. Dhulesia, G. Soldi, M. Vendruscolo, S.T. Hsu, F. Chiti, and C.M. Dobson, "Experimental Free Energy Surfaces Reveal the Mechanisms of Maintenance of Protein Solubility", Proc Natl Acad Sci USA 108, 21057-21062 (2011).

T.P.J. Knowles, C.A. Waudby, G.L. Devlin, S.A. Cohen, A. Aguzzi, M. Vendruscolo, E.M. Terentjev, M.E. Welland and C.M. Dobson, An Analytical Solution to the Kinetics of Breakable Filament Assembly, Science 326, 1533-1537 (2009)

S.T. Hsu, L.D. Cabrita, P. Fucini, J. Christodoulou and C.M. Dobson, Probing Side-chain Dynamics of a Ribosome-bound Nascent Chain using Methyl NMR Spectroscopy, J. Am. Chem. Soc., 131 (24), 8366-8367, (2009)

T.P. Knowles, A.W. Fitzpatrick, S. Meehan, H.R. Mott, M. Vendruscolo, C.M. Dobson and M.E. Welland, Role of Intermolecular Forces in Defining Material Properties of Protein Nanofibrils, Science 318, 1900-1903 (2007)

L.M. Luheshi, G.G. Tartaglia, A.C. Brorsson, A.P. Pawar, I.E. Watson, F. Chiti, M. Vendruscolo, D.A. Lomas, C.M. Dobson and D.C. Crowther, Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid Beta Pathogenicity, PloS Biol. 5(11):e290 (2007)

K. Lindorff-Larsen, R.B. Best, M.A. De Pristo, C.M. Dobson and M. Vendruscolo, Simultaneous Determination of Protein Structure and Dynamics, Nature 433, 129-133 (2005)

D.M. Korzhnev, X. Salvatella, M. Vendruscolo, A.A. Di Nardo, A.R. Davison, C.M. Dobson and L.E. Kay, Low Populated Folding Intermediates of the Fyn SH3 Domain Characterized by Relaxation Dispersion NMR, Nature 430, 586-590 (2004)

M. Dumoulin, A.M. Last, A. Desmyter, K. Decanniere, D. Canet, A. Spencer, D.B. Archer, S. Muyldermans, L. Wyns, A. Matagne, C. Redfield, C.V. Robinson and C.M. Dobson, A Camelid Antibody Fragment Inhibits Amyloid Fibril Formation by Human Lysozyme, Nature 424, 783-788 (2003)

F. Chiti, M. Stefani, N. Taddei, G. Ramponi and C.M. Dobson, Rationalisation of Mutational Effects on Protein Aggregation Rates, Nature 424, 805-808 (2003)

M. Fändrich, M.A. Fletcher and C.M. Dobson, Amyloid Fibrils from Muscle Myoglobin, Nature 410, 165-166 (2001)

M. Vendruscolo, E. Paci, C.M. Dobson and M. Karplus, Three Key Residues Form a Critical Contact Network in a Transition State for Protein Folding, Nature 409, 641-646 (2001)

Publications

Cooperative Assembly of Hsp70 Subdomain Clusters.
MA Wright, FA Aprile, MMJ Bellaiche, TCT Michaels, T Müller, P Arosio, M Vendruscolo, CM Dobson, TPJ Knowles
– Biochemistry
(2018)
Cholesterol catalyses A beta 42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes
J Habchi, S Chia, C Galvagnion, TCT Michaels, MMJ Bellaiche, FS Ruggeri, M Sanguanini, I Idini, JR Kumita, E Sparr, S Linse, CM Dobson, TPJ Knowles, M Vendruscolo
– Nature Chemistry
(2018)
10,
673
On-chip measurements of protein unfolding from direct observations of micron-scale diffusion.
Y Zhang, EV Yates, L Hong, KL Saar, G Meisl, CM Dobson, TPJ Knowles
– Chemical Science
(2018)
9,
3503
Molecular determinants of the interaction of EGCG with ordered and disordered proteins
G Fusco, M Sanz-Hernandez, FS Ruggeri, M Vendruscolo, CM Dobson, A De Simone
– Biopolymers
(2018)
e23117
Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding
F El Turk, E De Genst, T Guilliams, B Fauvet, M Hejjaoui, J Di Trani, A Chiki, A Mittermaier, M Vendruscolo, HA Lashuel, CM Dobson
– Protein Science
(2018)
Distinct thermodynamic signatures of oligomer generation in the aggregation of the amyloid-β peptide
SIA Cohen, R Cukalevski, TCT Michaels, A Šarić, M Törnquist, M Vendruscolo, CM Dobson, AK Buell, TPJ Knowles, S Linse
– Nature Chemistry
(2018)
10,
523
The small heat shock protein Hsp27 binds α-synuclein fibrils, preventing elongation and cytotoxicity.
D Cox, DR Whiten, JWP Brown, MH Horrocks, R San Gil, CM Dobson, D Klenerman, AM van Oijen, H Ecroyd
– J Biol Chem
(2018)
293,
4486
Correction to 'Bifunctional fluorescent probes for detection of amyloid aggregates and reactive oxygen species'.
L-M Needham, J Weber, JWB Fyfe, OM Kabia, DT Do, E Klimont, Y Zhang, M Rodrigues, CM Dobson, S Gandhi, SE Bohndiek, TN Snaddon, SF Lee
– Royal Society open science
(2018)
5,
180308
Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation
TCT Michaels, A Šarić, J Habchi, S Chia, G Meisl, M Vendruscolo, CM Dobson, TPJ Knowles
– Annu Rev Phys Chem
(2018)
69,
273
Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery
M Perni, PK Challa, JB Kirkegaard, R Limbocker, M Koopman, MC Hardenberg, P Sormanni, T Müller, KL Saar, LWY Roode, J Habchi, G Vecchi, N Fernando, S Casford, EAA Nollen, M Vendruscolo, CM Dobson, TPJ Knowles
– J Neurosci Methods
(2018)
  •  
  • 1 of 100
  • >

Research Interest Group

Telephone number

01223 763070 (shared)

Email address

cmd44@cam.ac.uk