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Professor Christopher Dobson FRS FMedSci

Portrait of cmd44

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);Chris Dobson Publications list (Microsoft Word).

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

Reviews

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

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

Interaction of the Molecular Chaperone DNAJB6 with Growing Amyloid-beta 42 (Aβ42) Aggregates Leads to Sub-stoichiometric Inhibition of Amyloid Formation.
C Månsson, P Arosio, R Hussein, HH Kampinga, RM Hashem, WC Boelens, CM Dobson, TP Knowles, S Linse, C Emanuelsson – J Biol Chem (2014) 289, 31066
Antibodies and protein misfolding: From structural research tools to therapeutic strategies
E De Genst, A Messer, CM Dobson – Biochimica et Biophysica Acta - Proteins and Proteomics (2014) 1844, 1907
The physical chemistry of the amyloid phenomenon: thermodynamics and kinetics of filamentous protein aggregation.
AK Buell, CM Dobson, TP Knowles – Essays Biochem (2014) 56, 11
Toxicity of protein oligomers is rationalized by a function combining size and surface hydrophobicity
B Mannini, E Mulvihill, C Sgromo, R Cascella, R Khodarahmi, M Ramazzotti, CM Dobson, C Cecchi, F Chiti – ACS Chem Biol (2014) 9, 2309
Differences in nucleation behavior underlie the contrasting aggregation kinetics of the A beta 40 and A beta 42 peptides
G Meisl, X Yang, E Hellstrand, B Frohm, JB Kirkegaard, SI Cohen, CM Dobson, S Linse, TP Knowles – Proceedings of the National Academy of Sciences of the United States of America (2014) 111, 9384
The amyloid state and its association with protein misfolding diseases.
TP Knowles, M Vendruscolo, CM Dobson – Nature Reviews Molecular Cell Biology (2014) 15, 384
Direct observations of amyloid β Self-assembly in live cells provide insights into differences in the kinetics of Aβ(1-40) and Aβ(1-42) aggregation
EK Esbjörner, F Chan, E Rees, M Erdelyi, LM Luheshi, CW Bertoncini, CF Kaminski, CM Dobson, GS Kaminski Schierle – Chemistry & Biology (2014) 21, 732
Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation
AK Buell, C Galvagnion, R Gaspar, E Sparr, M Vendruscolo, TP Knowles, S Linse, CM Dobson – Proceedings of the National Academy of Sciences of the United States of America (2014) 111, 7671
Hypochlorite-induced structural modifications enhance the chaperone activity of human alpha(2)-macroglobulin
AR Wyatt, JR Kumita, RW Mifsud, CA Gooden, MR Wilson, CM Dobson – Proceedings of the National Academy of Sciences of the United States of America (2014) 111, E2081
Understanding the influence of codon translation rates on cotranslational protein folding
EP O'Brien, P Ciryam, M Vendruscolo, CM Dobson – Accounts of Chemical Research (2014) 47, 1536
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Research Interest Groups

Telephone number

01223 763070 (shared)

Email address

cmd44@cam.ac.uk