Quantitative information about the molecules that participate in the basic processes of life, ideally in a physiological context, are key to understanding the physical principles that underly cellular organization and function. Self-association, oligomerization and/or aberrant aggregation is crucial for the (dys-)function of many proteins. However, access to molecular copy numbers and live cell studies of structure-function relationships at enhanced resolution in 3D are not yet generally available. Super-resolution optical fluctuation microscopy (SOFI) provides a promising alternative for extracting sub-diffraction information about molecular densities and properties of fluorescent probes. SOFI is readily usable at high label densities and moderate laser powers, which are favorable conditions for live cell imaging.
In this project, you will turn SOFI into a robust tool for measuring molecule numbers and reading of fluorescence blinking-based probes/sensors in 3D with the help of simulations and experiments with DNA & protein-based standards in vitro and in (live) cells. You will evaluate organic dyes and fluorescent proteins and also explore new classes of fluorophores. This includes different flavors of so-called self-blinking dyes. You will also use these spontaneously fluctuating dyes (no need for chemicals or high-power lasers) to push multicolor live-cell SOFI to higher resolution and to 3D time-lapse imaging.
You will be an integral part of our team and have the opportunity to build a state of-the-art 3D multicolor super-resolution microscope. Your work will also include collaborating on quantitative super-resolution microscopy (PALM/STORM/SOFI) within the Department of Bionanoscience and beyond! Depending on your scientific profile and interests, the specific focus of the project can be adjusted.
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