Dr Alexander Buell

Alexander Buell

University position

Senior Research Associate

Departments

Department of Chemistry

Home page

http://www.ch.cam.ac.uk/person/...

Research Theme

Cellular and Molecular Neuroscience

Interests

My research focuses on the kinetics and thermodynamics of biomolecular interactions, both in a functional and in a disease context. In particular, I aim to quantify the energy differences and energy barriers that are responsible for the transiion of soluble polypeptides into insoluble aggrgates. Such transitions are closely linked to a range of so called protein misfolding diseases, such as Alzheimer's and Parkinson's disease. A detailed understanding of the forces that lead to protein aggregation may enable us to control this process. Such understanding and control can also be useful in order to exploit peptide and protein self-assembly for novel materials.

Amyloid fibrils of the protein alpha-synuclein before and after contact with monomeric protein.
Amyloid fibrils of the protein alpha-synuclein before and after contact with monomeric protein.
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Research Focus

Keywords

amyloid

kinetics

biophysics

biosensing

self-assembly

Clinical conditions

Alzheimer's disease

Parkinson's disease

Equipment

No equipment indicated

Collaborators

Cambridge

Christopher Dobson

Clemens Kaminski

Tuomas Knowles

Michele Vendruscolo

International

Dieter Braun Web: http://www.biosystems.physik.uni-muenchen.de/

Ehud Gazit Web: http://www.tau.ac.il/lifesci...

Daniel Otzen Web: http://www.proteins.dk/

Associated News Items


Publications

2014

Cohen SI, Rajah L, Yoon CH, Buell AK, White DA, Sperling RA, Vendruscolo M, Terentjev EM, Dobson CM, Weitz DA, Knowles TP (2014), “Spatial propagation of protein polymerization.” Phys Rev Lett 112(9):098101 Details

Lorenzen N, Nielsen SB, Buell AK, Kaspersen JD, Arosio P, Vad BS, Paslawski W, Christiansen G, Valnickova-Hansen Z, Andreasen M, Enghild JJ, Pedersen JS, Dobson CM, Knowles TP, Otzen DE (2014), “The Role of Stable α-Synuclein Oligomers in the Molecular Events Underlying Amyloid Formation.” J Am Chem Soc 136(10):3859-68 Details

Mason TO, Chirgadze DY, Levin A, Adler-Abramovich L, Gazit E, Knowles TP, Buell AK (2014), “Expanding the solvent chemical space for self-assembly of dipeptide nanostructures.” ACS Nano 8(2):1243-53 Details

Pinotsi D, Buell AK, Galvagnion C, Dobson CM, Kaminski Schierle GS, Kaminski CF (2014), “Direct observation of heterogeneous amyloid fibril growth kinetics via two-color super-resolution microscopy.” Nano Lett 14(1):339-45 Details

Tóth G, Gardai SJ, Zago W, Bertoncini CW, Cremades N, Roy SL, Tambe MA, Rochet JC, Galvagnion C, Skibinski G, Finkbeiner S, Bova M, Regnstrom K, Chiou SS, Johnston J, Callaway K, Anderson JP, Jobling MF, Buell AK, Yednock TA, Knowles TP, Vendruscolo M, Christodoulou J, Dobson CM, Schenk D, McConlogue L (2014), “Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein by Small Molecules as a Potential Therapeutic Strategy for Parkinson's Disease.” PLoS One 9(2):e87133 Details

2013

Buell AK, Hung P, Salvatella X, Welland ME, Dobson CM, Knowles TP (2013), “Electrostatic effects in filamentous protein aggregation.” Biophys J 104(5):1116-26 Details

Guilliams T, El-Turk F, Buell AK, O'Day EM, Aprile FA, Esbjörner EK, Vendruscolo M, Cremades N, Pardon E, Wyns L, Welland ME, Steyaert J, Christodoulou J, Dobson CM, De Genst E (2013), “Nanobodies raised against monomeric α-synuclein distinguish between fibrils at different maturation stages.” J Mol Biol 425(14):2397-411 Details

Pica A, Merlino A, Buell AK, Knowles TP, Pizzo E, D'Alessio G, Sica F, Mazzarella L (2013), “Three-dimensional domain swapping and supramolecular protein assembly: insights from the X-ray structure of a dimeric swapped variant of human pancreatic RNase.” Acta Crystallogr D Biol Crystallogr 69(Pt 10):2116-23 Details

Pinotsi D, Buell AK, Dobson CM, Kaminski Schierle GS, Kaminski CF (2013), “A label-free, quantitative assay of amyloid fibril growth based on intrinsic fluorescence.” Chembiochem 14(7):846-50 Details

Xu LQ, Wu S, Buell AK, Cohen SI, Chen LJ, Hu WH, Cusack SA, Itzhaki LS, Zhang H, Knowles TP, Dobson CM, Welland ME, Jones GW, Perrett S (2013), “Influence of specific HSP70 domains on fibril formation of the yeast prion protein Ure2.” Philos Trans R Soc Lond B Biol Sci 368(1617):20110410 Details

2012

Buell AK, Dhulesia A, White DA, Knowles TP, Dobson CM, Welland ME (2012), “Detailed analysis of the energy barriers for amyloid fibril growth.” Angew Chem Int Ed Engl 51(21):5247-51 Details

Buell AK, Dobson CM, Welland ME (2012), “Measuring the kinetics of amyloid fibril elongation using quartz crystal microbalances.” Methods Mol Biol 849:101-19 Details

Roodveldt C, Andersson A, De Genst EJ, Labrador-Garrido A, Buell AK, Dobson CM, Tartaglia GG, Vendruscolo M (2012), “A rationally designed six-residue swap generates comparability in the aggregation behavior of α-synuclein and β-synuclein.” Biochemistry 51(44):8771-8 Details

2011

Buell AK, Dhulesia A, Mossuto MF, Cremades N, Kumita JR, Dumoulin M, Welland ME, Knowles TP, Salvatella X, Dobson CM (2011), “Population of nonnative states of lysozyme variants drives amyloid fibril formation.” J Am Chem Soc 133(20):7737-43 Details

Buell AK, Esbjörner EK, Riss PJ, White DA, Aigbirhio FI, Toth G, Welland ME, Dobson CM, Knowles TP (2011), “Probing small molecule binding to amyloid fibrils.” Phys Chem Chem Phys 13(45):20044-52 Details

Shammas SL, Waudby CA, Wang S, Buell AK, Knowles TP, Ecroyd H, Welland ME, Carver JA, Dobson CM, Meehan S (2011), “Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation.” Biophys J 101(7):1681-9 Details

Wang YQ, Buell AK, Wang XY, Welland ME, Dobson CM, Knowles TP, Perrett S (2011), “Relationship between prion propensity and the rates of individual molecular steps of fibril assembly.” J Biol Chem 286(14):12101-7 Details

2010

Buell AK, Blundell JR, Dobson CM, Welland ME, Terentjev EM, Knowles TP (2010), “Frequency factors in a landscape model of filamentous protein aggregation.” Phys Rev Lett 104(22):228101 Details

Buell AK, Dobson CM, Knowles TP, Welland ME (2010), “Interactions between amyloidophilic dyes and their relevance to studies of amyloid inhibitors.” Biophys J 99(10):3492-7 Details

Buell AK, White DA, Meier C, Welland ME, Knowles TP, Dobson CM (2010), “Surface attachment of protein fibrils via covalent modification strategies.” J Phys Chem B 114(34):10925-38 Details

Knowles TP, Oppenheim TW, Buell AK, Chirgadze DY, Welland ME (2010), “Nanostructured films from hierarchical self-assembly of amyloidogenic proteins.” Nat Nanotechnol 5(3):204-7 Details

White DA, Buell AK, Knowles TP, Welland ME, Dobson CM (2010), “Protein aggregation in crowded environments.” J Am Chem Soc 132(14):5170-5 Details

2009

Buell AK, Tartaglia GG, Birkett NR, Waudby CA, Vendruscolo M, Salvatella X, Welland ME, Dobson CM, Knowles TP (2009), “Position-dependent electrostatic protection against protein aggregation.” Chembiochem 10(8):1309-12 Details

White DA, Buell AK, Dobson CM, Welland ME, Knowles TP (2009), “Biosensor-based label-free assays of amyloid growth.” FEBS Lett 583(16):2587-92 Details