Summary
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.
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.
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| Web resources: | https://cordis.europa.eu/project/id/101065980 |
| Start date: | 01-01-2023 |
| End date: | 31-12-2024 |
| Total budget - Public funding: | - 173 847,00 Euro |
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Original description
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.
Status
SIGNEDCall topic
HORIZON-MSCA-2021-PF-01-01Update Date
09-02-2023
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