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  Advanced multi-colour super-resolution imaging


   Department of Physics

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  Dr S Van de Linde  Applications accepted all year round

About the Project

This interdisciplinary PhD project aims to develop novel fluorescent probes and imaging schemes for multicolour super-resolution microscopy, which can lead to biological understanding and underpin future improvements in healthcare.

Fluorescence microscopy is the method of choice to study cells in a comparatively non-invasive way. With the development of super-resolution methods (awarded the 2014 Nobel Prize in Chemistry) the classical ~200 nm diffraction limit can be overcome. Achieving resolutions <20 nm, super-resolution microscopy has found wide-spread applications in different fields of biology.
Within the family of super-resolution techniques single-molecule localization microscopy (SMLM) stands out as it provides, besides highest spatial resolution, also quantitative information.
The group is developing a very common technique termed direct stochastic optical reconstruction microscopy (dSTORM), which is based on organic dyes that are made photoswitchable by using chemical buffers. These dyes are small, chemically modifiable, and can be used for stoichiometric labelling of almost any protein even in living cells.

dSTORM enables fascinating insights into the structural organization of a cell, but requires extremely reliable molecular photoswitches and is often limited to a single colour. The goal of the PhD project is to develop advanced multicolour photoswitches in the far-red / near-infrared spectral region with an emphasis on imaging proteins in the inner mitochondrial membrane.

The successful candidate will be placed in a very interdisciplinary research environment with full access to the fluorescence spectroscopic infrastructure of the group. He/She will gain strong expertise in single-molecule based super-resolution microscopy, microscopic hardware, developing software for image processing and data analysis, designing fluorophore labelled probes, preparing and labelling biological samples, as well as collaborating with biological research partners.

Key words: super-resolution, dSTORM, multi-colour imaging, cellular imaging, three-dimensional imaging


Funding Notes

Project will be funded by a Strathclyde University studentship - eligibility for a full scholarship is limited to EU citizens

References

Direct stochastic optical reconstruction microscopy with standard fluorescent probes.
van de Linde S, Löschberger A, Klein T, Heidbreder M, Wolter S, Heilemann M, Sauer M.
Nat Protoc. 2011, 6, 991-1009. doi: 10.1038/nprot.2011.336.

How to switch a fluorophore: from undesired blinking to controlled photoswitching.
van de Linde S, Sauer M. Chem Soc Rev. 2014, 43, 1076-87. doi: 10.1039/c3cs60195a.

Photometry unlocks 3D information from 2D localization microscopy data. Franke C, Sauer M, van de Linde S. Nat Methods, 2017, 14, 41-44. doi: 10.1038/nmeth.4073.

Where will I study?