Arbeitsgruppe Buell

Welcome to the web page of the Buell group. Below you can find an overview over our research interests. Please get in touch if you are interested in joining our efforts in understanding the molecular mechanisms of protein aggregation. For an up-to-date overview of the topics we are interested in, you can refer to the publication list on google scholar.

Research Topics

1) The physical chemistry of peptide and protein self-assembly.

Normally, proteins are required to be soluble, in order to be functional. However, in some cases, proteins and peptides are observed to aggregate into insoluble structures, that can be ordered or amorphous. Amyloid fibrils are highly ordered, homopolymeric protein aggregates, and are found in the context of a range of diseases, such as Alzheimer's and Parkinson's diseases. It has been proposed that the aggregated state represents the thermodynamically most favourable state of any protein. However, it is not known why that is the case, and how proteins achieve to remain soluble in most cases. We apply a range of biophysical tools, such as calorimetry, biosensing and fluorescence spectroscopy for the study of the kinetics and thermodynamics of amyloid formation in order to answer these questions.

Literature examples:

- Buell et al., Detailed analysis of the energy barriers for amyloid fibril growth, Angew. Chem. Int. Ed. 2012, 51, 5247-5251

- Buell et al., Electrostatic effects in filamentous protein aggregation, Biophysical Journal 2013, 104, 1116-1126

- Buell et al., The physical chemistry of the amyloid phenomenon: thermodynamics and kinetics of filamentous protein aggregation, Essays Biochem. 2014, 56, 11-39

- Buell, A, The nucleation of protein aggregates, from crystals to amyloid fibrils, International Review of Cell and Molecular Biology 2017, 329, 187-226

2) The mechanism of α-synuclein amyloid formation.

Amyloid fibrils of the intrinsically disordered protein α-synuclein are the main component of Lewy bodies, intra-neuronal inclusions that characterise the pathology of Parkinson's disease. We aim to understand the mechanism of transformation of α-synuclein from its disordered monomeric state in solution into the highly ordered, β-sheet rich amyloid state.

Literature examples:

- Buell et al., Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation, PNAS 2014, 111(21), 7671-7676

- Galvagnion et al., Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation, Nat. Chem. Biol. 2015, 11, 229-234

- Flagmeier et al., Mutations associated with familial Parkinson's disease alter the initiation and amplification steps of α-synuclein aggregation, PNAS 2016, 113, 10328-10333

- Brown et al., β-Synuclein suppresses both the initiation and amplification steps of α-synuclein aggregation via competitive binding to surfaces, Scientific Reports 2016, 6, 36010

3) Exploiting peptide self-assembly for materials science.

Peptide and protein aggregates are not only associated with disease, they also have remarkable mechanical and structural properties. Nature exploits these properties in the case of functional amyloid fibrils, for example for bacterial or fungal adhesion and melanin biosynthesis. We are aiming to understand and control the self-assembly of simple peptides, which are not linked to disease, into interesting and useful materials.

Literature example:

- Mason et al., Expanding the solvent chemical space for self-assembly of peptide nanostructures, ACS Nano 2014, 8, 1243-1253

- Mason et al., Synthesis of Nonequilibrium Supramolecular Peptide Polymers on a Microfluidic Platform, JACS 2016, 138(30), 9589-9596

- Mason et al., Thermodynamics of polypeptide self-assembly in the short chain limit, JACS 2017, 139 (45), 16134–16142

Physikalische Biologie
Gebäude 26.12, Ebene U1
Universitätsstraße 1
40225 Düsseldorf

Prof. Dr. D. Willbold
Gebäude 26.12
Ebene U1, Raum 84
Telefon: +49-(0)211 / 81-11390
Mail senden


Jun. Prof. Dr. Alexander K. Buell

Universitätsstrasse 1
Gebäude: 26.11
Etage/Raum: U1.24
40225 Düsseldorf
Tel.: +49 211 81-15575
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