C:\Users\Dreamcatcher\Desktop\New folder\photo.JPGIn 2002, Niels started his study applied physics at the University of Twente. After his Bachelor's assignment at the Optical Sciences group, he decided to focus on the optics and biophysics track. He completed an internship at the Ultrafast and Microspectroscopy Laboratories at the University of Melbourne on the topic of Structured Illumination Microscopy, followed by a Master's assignment at the Complex Photonic Systems (COPS) group in close collaboration with the Nanobiophysics (NBP) group. During his Master's thesis, he investigated the influence of the local density of optical states on Förster resonance energy transfer (FRET). After finishing his Master's assignment in 2009, he decided to join the NBP group where he is currently doing research on the characterization of the structures and compositions of the alpha-synuclein oligomeric species using high-resolution, ultrasensitive optical microscopy.

-Contact Information –

Niels Zijlstra

Nanobiophysics (NBP) group

MESA+ Institute for Nanotechnology

University of Twente

Room: Zuidhorst ZH151

PO Box 217

7500 AE Enschede

The Netherlands

T: +31 (0)53 489 3359

F: +31 (0)53 489 2150


Research topic: Using single-molecule approaches to characterize alpha-synuclein oligomers

The neuronal protein alpha-synuclein is considered to play a critical role in the onset and progression of Parkinson’s disease. Fibrillar aggregates of alpha-synuclein are the main constituents of the Lewy bodies that are found in the brains of Parkinson patients. However, there is growing evidence suggesting that oligomeric aggregates are significantly more toxic to cells than fibrillar aggregates. Molecular insights into the structure and composition of these oligomeric aggregates are therefore essential for understanding the aggregation process and, ultimately, the cause of the disease. Despite the fact that the oligomeric form is a very important intermediate species, information on the structural and compositional properties is very limited, due to the extremely low concentrations and transient nature of these oligomers.

In this project we will use single-molecule approaches to gain insight into the composition and structure of these oligomeric species. We will determine the composition of the oligomeric species using single-molecule photobleaching approaches, while the structure can be elucidated using single-pair FRET measurements.

C:\Users\Dreamcatcher\Desktop\aggregation process.jpg

Figure 1: Schematic representation of the aggregation process of α-synuclein. The possible toxic species are the intermediate aggregates, called oligomers. In real life, the aggregation process is much more complex and many more species exist.


Structural and Compositional Information about Pre-Amyloid Oligomers

N. Zijlstra, V. Subramaniam

in Amyloid Fibrils and Prefibrillar Aggregates: Molecular and Biological Properties (ed. D. E. Otzen),

Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany.

doi: 10.1002/9783527654185.ch6

C:\Users\Dreamcatcher\Desktop\PRL.jpgNanophotonic Control of the Förster Resonance Energy Transfer Efficiency

C. Blum, N. Zijlstra, A. Lagendijk, M. Wubs, A.P. Mosk, V. Subramaniam, W.L. Vos
Physical Review Letters
, 109, 203601 (2012)

doi: 10.1103/PhysRevLett.109.203601

Featured e.g. in:


Science – Editors Choice: Don’t FRET – All Under Control


Nature Materials – Research Highlights: Molecular energy transfer


Interview on Dutch radio show Hoe?Zo! Radio

α-Synuclein Oligomers: an Amyloid Pore? Insights into Mechanisms of α-Synuclein Oligomer–Lipid Interactions

M.T. Stöckl, N. Zijlstra, V. Subramaniam

Molecular Neurobiology

doi: 10.1007/s12035-012-8331-4

C:\Users\Dreamcatcher\Desktop\Angewandte.jpgMolecular Composition of Sub-stoichiometrically Labeled α-Synuclein Oligomers

Determined by Single-Molecule Photobleaching

N. Zijlstra, C. Blum, I.M.J. Segers-Nolten, M.M.A.E. Claessens, V. Subramaniam
Angewandte Chemie International Edition
, Volume 51, Issue 35, pages 8821–8824 (2012)

doi: 10.1002/anie.201200813

Featured e.g. in Dutch press:


Kennislink: Eiwitten tellen met licht


Chemisch Weekblad: Substoichiometrische eiwittenteller

Locally resolved membrane binding affinity of the α-Synuclein N-terminus

M. Robotta, C. Hintze, S. Schildknecht, N. Zijlstra, C. Jüngst, C. Karreman, M. Huber, M. Leist, V. Subramaniam, M. Drescher

Biochemistry, 2012, 51 (19), pp 3960–3962

doi: 10.1021/bi300357a

Nanobiophotonics: using the nanophotonics toolbox to manipulate biological fluorophores

C. Blum, N. Zijlstra, Y. Cesa, V. Subramaniam, J.M. van den Broek, A.P. Mosk, W.L. Vos

International Workshop on BioPhotonics 2011