Lecture: Physico-chemical studies of polypeptide self-assembly and protein aggregation

06.03.2017, 10:00

Prof. Alexander Büll, Institute of Physical Biology, Heinrich-Heine-Universität Düsseldorf

Time, place:
Monday, 6th March 2017, 10:00h
Seminar Room A1.500, MPL, Staudtstr. 2, 91058 Erlangen


In this seminar I will aim to give a comprehensive but compact overview over my past and present research activities in the field of peptide self-assembly and protein aggregation into amyloid fibrils. In the light of a planned extended stay in Erlangen in the near future, I think it is most useful if I give an as wide as possible overview over my interests in order to facilitate potential collaborations.

I am interested in elucidating the fundamental driving forces and mechanisms of biomolecular self-assembly into supramolecular structures, such as amyloid fibrils and peptide crystals. Amyloid fibrils are highly ordered homopolymeric protein filaments that are a hallmark of several severe neurodegenerative diseases, such as Alzheimer's and Parkinson's. However, in some cases amyloid fibrils can provide biological functions as well, or they can even be used for the production of novel materials.

I will discuss biosensing approaches that allow the kinetics of amyloid fibril growth to be measured accurately and in real time. This approach was used to study the dependence of this process on temperature, ionic strength and changes in protein sequence and solution conditions.

Furthermore, I will discuss mechanistic studies of the self-assembly processes of short model peptides into crystalline structures, using microfluidic flow reactors amongst other techniques. I will also discuss the thermophoretic behavior of protein aggregates.

The last part of the seminar will be dedicated to mechanistic studies of the intrinsically disordered protein alpha-synuclein, the amyloid formation of which is a hallmark of Parkinson's disease. In particular I will present data that demonstrates the existence of an autocatalytic process that leads to the exponential proliferation of the aggregates.



Selected references:

-        Buell AK et al.,Frequency factors in a landscape model of filamentous protein aggregation, Phys Rev Lett 2010

-        Buell AK et al., Population of nonnative States of lysozyme variants drives amyloid fibril formation, JACS 2011

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

-        Buell AK, et al., Electrostatic effects in filamentous protein aggregation, Biophys J. 2013

-        Buell AK et al., Solution conditions determine the relative importance of nucleation and growth processes in alpha-synuclein aggregation, PNAS 2014

-        Mason et al., Expanding the solvent chemical space for self-assembly of dipeptide nanostructures, ACS Nano 2014

-        Mason et al., Synthesis of Nonequilibrium Supramolecular Peptide Polymers on a Microfluidic Platform, JACS 2016

-        Wolff et al., Quantitative thermophoretic study of disease-related protein aggregates, Scientific Reports 2016

-        Buell AK, The nucleation of protein aggregates – from crystals to amyloid fibrils, Int rev. Cell. Mol. Biol. 2017