The conventional detection of proteins by imaging employs fluorophores or antibodies directed at individual proteins. However, this methodology cannot be upscaled and employed in a high-throughput omics approach. The EU-funded IMAGEOMICS project aims to address this limitation through affinity probes that bind to specific peptide sequences located in more than one protein. Scientists will develop nanobodies that bind to such peptides and use them to label biological samples. The IMAGEOMICS strategy will provide information on the whole proteome of cells and tissues, paving the way for improved diagnostics for various diseases.
Our project combines several scientific disciplines. First, bioinformatics at UMG already provided our set of target peptide sequences, and will enable us to interpret the combinatorial images. Second, biochemistry and probe development (life sciences) will provide the nanobodies. Third, microfluidics (engineering) will be necessary to validate the optimal nanobodies and their application. Fourth, complex sample preparation and expansion, driven by biological engineering, will enable us to obtain suitable samples. Fifth, advances in optical physics and in optical microscopy design, driven by physicists, will implement the imaging technology.
We propose here to develop a technology that will provide nanoscale proteomic images for biomedical research. If successful, this technology will replace conventional assays implemented with antibodies, as Western Blot, immunostaining or immunohistochemistry, with a more efficient and wide-ranging method. This should have large economic implications, as we expect that a significant fraction of the commercial biomedical assays currently undertaken with antibodies will be replaced by our technology. Importantly, our technology could also be applied to the identification of novel pathogens in human samples, as long as their genomic sequences are known, without the need of novel (specific) imaging tools.
This project receives funding from the European’s Union Horizon 2020 Horizon research and innovation programme under grant agreement No 964016 (FET-OPEN Call 2020, IMAGEOMICS project).
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Hello world, ONE is here… I am happy to share with you a new technology —termed #ONE_Microscopy, that allows a resolution approaching ~8 Å using conventional light microscopy.@LabSauer @eboyden3 @RaduAricescu— Ali H. Shaib (@AliHShaib) August 6, 2022
Full story:https://t.co/uxUZTUZeYl pic.twitter.com/75SUQpCrbJ
As promised, we now present to you the full power of #ONE_Microscopy by describing molecular organisation of proteins. Truly, bridging the gap between fluorescence microscopy and Cryo-EM.— Ali H. Shaib (@AliHShaib) March 10, 2023
Plus 25 more datasets…https://t.co/JYOZkNOIgc@eboyden3 @RaduAricescu @LabSauer & Rizzoli pic.twitter.com/aLmidgl9Ct
The shape of single proteins seen with light microscopy. #ONE_Microscopy combines the power of expansion microscopy with SRRF analysis. 🔬https://t.co/6LTTUjUsdH@MforMicroscaya covers a great #preprint describing #ExM at 1 nm resolution. Includes authors’ comments @AliHShaib! pic.twitter.com/Mm2t2WG5TO— preLights (@preLights) November 25, 2022
The revolution will not be vitrified! Move over #cryoEM & #cryoET, welcome #ONE_Microscopy 😍https://t.co/dxkkqBk1bI Amazing work from @AliHShaib and the Rizzoli lab, building on concepts from @eboyden3 and @HenriquesLab. With a #GABAA receptor teaser from @danielmihaylov7 😉— Radu Aricescu (@RaduAricescu) August 6, 2022
😍 Holy Moly! @AliHShaib just established ONE, a method combining #ExM and #SRRF to achieve one nanometre resolution imaging on most microscopes! Figures are beyond super!! Congratulations everyone, can't wait to try it https://t.co/973cJEmc0b pic.twitter.com/NIgV6zeGTj— Ricardo Henriques (@HenriquesLab) August 6, 2022
Preprint on an expansion microscopy method that reports achieving 1 nm resolution using 10x expansion, covalent fluorophore addition to proteins after breaking and expanding, and intensity fluctuation analysis https://t.co/fwcpjfAU2p pic.twitter.com/5dh62YRc5T— Tim Stearns (@StearnsLab) August 6, 2022
What a wonderful Triangulate Smart Ruler (TSR) tool from @_NanoTag_ !— Ali H. Shaib (@AliHShaib) August 6, 2022
How small is small?
It took us a while to think about a target that we could use to validate our practical resolution. @FelipeOpaz_o came to the rescue with the TSR design.
Very cool work!!! Silvio showed me the data when I was there. Quite excited about it's application. Especially, happy to see one of my favorite proteins in the world - Otoferlin !— Rituparna Chakrabarti 🔬🧠☕ (@RituChakra) August 6, 2022