Method development
Description
Methods and technologies for cell analysis are a cornerstone in research and healthcare, facilitating researchers in answering questions about the origins and progression of disease, and helping clinicians to set a correct diagnosis. Over the last two decades we have mainly focused on the development of methods; such as in situ PLA, ProxHCR and MolBoolean; to provide the ability to monitor protein-protein interactions and post-translational modifications in fixed cells and tissues, which is essential for the studies and understanding of cellular signaling. These methods use DNA as a reporter molecule and are based on natural occurring enzymes. Our current research explores the possibility to go beyond the boundaries of what nature can provide, to design enzymes that cannot be made through evolution. We have recently engineered a DNA-polymerase that isn´t compatible with life, that provides unique opportunities for development of novel methods for medical research.
Selected publications
Publications and Bibliometrics
Google scholar
https://scholar.google.se/citationsuser=XigDIwUAAAAJ&hl=en&oi=ao
Scopus:
https://www.scopus.com/authid/detail.uri?authorId=57204274888
Bivehed E, Hellman B, Wenson L, Stenerlöw B, Söderberg O & Heldin J
”Visualizing DNA single- and double-strand breaks in the Flash comet assay by DNA polymerase assisted end-labelling”
Nucleic Acid Res, 2024, in press
Raykova D, Kermpatsou D, Malmqvist T, Harrison PJ, Rubin Sander M, Stiller C, Heldin J, Leino M, Ricardo S, Klemm A, David L, Spjuth O, Vemuri K, Dimberg A, Sundqvist A, Norlin M, Klaesson A, Kampf C & Söderberg O
“A method for Boolean Analysis of Protein Interactions at a Molecular Level”
Nature Communications, 2022, 13(1):4755
Koos B, Cane G, Grannas K, Löf L, Arngården L, Heldin J, Clausson CM, Klaesson A, Hirvonen MK, Souza de Oliviera FM, Talibov V, Pham N, Auer M, Danielson H, Haybaeck J, Kamali-Moghaddam M & Söderberg O
“Proximity dependent initiation of hybridization chain reaction”
Nature Communications, 2015, 6, 7294
Leuchowius KJ, Clausson CM, Grannas K, Erbilgin Y, Botling J, Zieba A, Landegren U & Söderberg O.
”Parallel visualization of multiple protein complexes in individual cells in tumor tissue”
Mol Cell Proteomics, 2013, 12(6):1563-71.
Weibrecht I, Lundin E, Kiflemariam S, Mignardi M, Grundberg I, Larsson C, Koos B, Nilsson M & Söderberg O.
”In situ detection of individual mRNA molecules and protein complexes or post-translational modifications using padlock probes combined with the in situ proximity ligation assay”
Nature Protocols, 2013, 8(2): 355-72.
Weibrecht I, Gavrilovic M, Lindbom L, Landegren U, Wählby C & Söderberg O.
”Visualising individual sequence-specific protein-DNA interactions in situ”
N Biotechnol, 2012, 29(5): 589-598.
Clausson CM, Allalou A, Weibrecht I, Mahmoudi S, Farnebo M, Landegren U, Wählby C & Söderberg O.
”Increasing the dynamic range of in situ PLA”
Nature Methods, 2011, 8(11): 892-893.
Larsson C, Grundberg I, Söderberg O & Nilsson M.
”In situ detection and genotyping of individual mRNA molecules”
Nature Methods, 2010, 7(5): 395-397.
Jarvius M, Paulsson J, Weibrecht I, Leuchowius KJ, Andersson AC, Wählby C, Gullberg M, Botling J, Sjöblom T, Markova B, Östman A, Landegren U & Söderberg O.
”Detection of PDGF-receptor-β phosphorylation using a generalized proximity ligation method”
Mol Cell Proteomics, 2007, 6(9): 1500-1509.
Söderberg O, Gullberg M, Jarvius M, Ridderstråle K, Leuchowius KJ, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson LG & Landegren U.
”Direct observation in situ of individual endogenous protein complexes by proximity ligation”
Nature Methods, 2006, 3(12): 995-1000.
Doctoral dissertations from the group
2010
Karl-Johan Leuchowius ” High Content Analysis of Proteins and Protein Interactions by Proximity Ligation”
http://uu.diva-portal.org/smash/get/diva2:301950/FULLTEXT01.pdf
2011
Irene Weibrecht “Visualizing Interacting Biomolecules In Situ”
http://uu.diva-portal.org/smash/get/diva2:410507/FULLTEXT01.pdf
2012
Agata Zieba “Application of Proximity Ligation Assay for Multidirectional Studies on Transforming Growth Factor Receptor-β Pathway”
http://uu.diva-portal.org/smash/get/diva2:513327/FULLTEXT01.pdf
2014
Carl-Magnus Clausson “Making Visible the Proximity Between Proteins”
http://uu.diva-portal.org/smash/get/diva2:695615/FULLTEXT01.pdf
2015
Karin Grannas “Improvements and Applications of in situ Proximity Ligation Assays”
http://uu.diva-portal.org/smash/get/diva2:801280/FULLTEXT01.pdf
2016
Linda Arngården “Analysis of signaling pathway activity in single cells using the in situ Proximity Ligation Assay”
http://uu.diva-portal.org/smash/get/diva2:915351/FULLTEXT01.pdf
2018
Axel Klaesson “Development of DNA-based methods for analysis of protein interactions”
http://uu.diva-portal.org/smash/get/diva2:1177746/FULLTEXT01.pdf
2023
Despoina Kermpatsou ”Method development for analysis of protein interactions”
http://uu.diva-portal.org/smash/get/diva2:1712557/FULLTEXT01.pdf
Mattias Leino “Advancing DNA-based proximity methods”
http://uu.diva-portal.org/smash/get/diva2:1740390/FULLTEXT01.pdf
Marie Rubin Sander “Analysis of PDGF receptor internalization and signaling using proximity ligation assays”
http://uu.diva-portal.org/smash/get/diva2:1742559/FULLTEXT01.pdf