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Intramolecular optical microscopy with sub-nm spatial resolution in single biomolecules and single-protein sequencing

Objective

Fluorescence microscopy has witnessed a true resolution revolution in the past decades. The invention of methods circumventing the classical diffraction limit of ≈200 nm has allowed researchers – for the first time – to reach sub-diffraction resolution with optical fluorescence microscopy. With these so-called super-resolution techniques, processes within cells can be observed at thus far unprecedented spatial resolutions.
However, while incumbent super-resolution approaches enable researchers to resolve intermolecular distances between e.g. protein molecules in small protein clusters, the final frontier in optical bioimaging to resolve intramolecular distances in the sub-nm regime for single molecules is still elusive. With this research proposal, I want to develop and apply a paradigm-shifting imaging technology that allows intramolecular optical microscopy with sub-nm spatial resolution in single biomolecules.
To achieve this goal, I will combine DNA-Point Accumulation Imaging Nanoscale Topography (DNA-PAINT) with DNA Exchange to overcome the current limit of optical nanoscopy in terms of spatial resolution. To do so, I will build a microscope with ultra-high stability and sensitivity. The project is conceived as an integral approach including the design of optics, instrumentation, labelling probes and data analysis.
Such a capability provided by the project IntraMol would be a game changer in fluorescence microscopy, as it could – for the first time – allow scientists to resolve intramolecular distances e.g. within single proteins, thus enabling structural biology studies and provide insights into conformations of proteins even enable single-molecule protein sequencing using optical microscopy in situ.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) HORIZON-MSCA-2021-PF-01

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 173 847,36
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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