„”
Our lab is looking for new ways to visualize and interrogate biological function, such as cell signalling or protein dynamics.
Putting the spotlight on the invisible to see more in research. Our expertise lies in the development of synthetic, custom-tailored fluorescent substrates to be used in microscopy. We think in and pursue unconventional ways in the design and synthesis of fluorophores for high-definition imaging in living cells.
Probes for compartmentalized labelling
In a dynamic cellular environment, proteins move and reside in different compartments. Accordingly, ways have to be found to label the same proteins differently when they are not at locations. Tuning the SNAP-tag substrate BG to its sulfonated version SBG, fluorophores are endowed with an impermeable leaving group. Besides better solubility, no evaluation of the cargo is needed as it stays untouched; and as such, any desired fluorophore can be employed to only label the surface exposed pool of a protein. Showcasing this for a member of every G protein-coupled receptor (GPCR) class, we performed super resolution microscopy, protein tracking of turnover and stoichiometry measurements of different receptor pools.
Endogenous protein labelling
Attaching fluorophores to peptidic antagonists of GLP1R, a protein involved in glucose homeostasis and appetite regulation, we endowed this receptor in its native environment with a dye. As such, we are able to closely look where it resides in the cell, with ramifications for the understanding of protein dynamics and generation of specific markers for differentiated stem cells.
Photocontrolling GPCRs
G protein-coupled receptors are cell surface proteins that sense stimuli outside of the cell and translate this into an intracellular response. Albeit being the largest drug target, the activation mechanism and fine interplay remain partly understood. Using a combination of photoswitchable molecules with protein engineering, we are able to use light with its unique spatiotemporal resolution to remote- and precise-control metabotropic glutamate receptors, key players in health and disease in the nervous system. Recently, quantitative efficacy was achieved for the first time by increasing the valency of our photoswitches – a chemical trick that might be amenable to other targets.
The LUXendins describe antagonistic, fluorophore-fused peptides against the glucagon-like peptide-1 receptor (GLP1R), a class B GPCR involved in glucose homeostasis and a blockbuster drug target. With our different availbale colours (LUXendin555, LUXendin645 and LUXendin651) we are able to visualize, track and assay this receptor in live cells and tissue. Indeed, this leads to insights in localization by super-resolution microscopy and movement i ...
LABELLING ENDOGENOUS PROTEINS
Several techniques are available to label proteins, some of which need genetic engineering. We aim to visualize endogenous proteins by means of microscopy to learn about their localization and behaviour. This is achieved by carefully designing specific probes consisting of tight binders chemically fused to an appropriate marker. As such, we are able to look at distribution and dynamics of cell surface proteins on th ...
Photopharmacology is a powerful method to manipulate biological function with the spatiotemporal resolution light offers. This is achieved by endowing pharmacophores with a light responsive chemical group. While this approach has come up with a variety of targetable biomolecules, we aim to find ways to improve this to the quantitative level using nanobodies in combination with fine-tuned, fluorescent and multivalent photoswitches. Farrants et al. ...
CHEMICAL SYNTHESIS "A round bottom flask was charged with ...." We use the power of organic chemistry to molecules to fine-tune pharmacological properties, introducing subtype selectivity for protein families or signal bias for cellular communication. Jones et al., ChemistryOpen 2017;Häfner et al., ChemMedChem 2018
DEUTERATED RHODAMINES We develop and use "d12" deuterium congeners of rhodamines that exhibit higher brightness and longer lifetimes with reduced bleaching versus their parent fluorophores TMR and SiR. Have a look at improved Förster resonance energy transfer (FRET), fluorescence activated cell sorting (FACS), fluorescence lifetime microscopy (FLIM) and stimulated emission depletion (STED) nanoscopy in our latest preprint. Roßmann et al., bioRxiv ...
Photopharmacology is a powerful method to manipulate biological function with the spatiotemporal resolution light offers. This is achieved by endowing pharmacophores with a light responsive chemical group. While this approach has come up with a variety of targetable biomolecules, we aim to find ways to improve this to the quantitative level using nanobodies in combination with fine-tuned, fluorescent and multivalent photoswitches.
Sommer 2023
January 2023
June 2022
June 2021
November 2020
People
After studying Chemistry in Erlangen with a one-year stint in the Weck group at NYU, JB graduated from the lab of Ivana Ivanovic-Burmazovic in 2010. Interested in biology, he joined the lab of Dirk Trauner at LMU Munich, obtaining his PhD in 2014 and pursuing his endeavours with Kai Johnsson, first at EPFL, then at the Max Planck for Medical Research in Heidelberg. He joined the FMP in 2020 as a Junior Group Leader in Chemical Biology.
Souvik completed his Integrated M.Sc in Chemistry from S.V. National Institute of Technology, India. Then, he move to Bremen, Germany to pursue his PhD in 2018. He designed and synthesized a series of photoswitchable azobenzene macrocycles and investigated their photophysical properties during his PhD. Afterwards, he joined JB's lab, focusing on the development of deuterated compounds for sensitive microscopy.
Blaise studied chemistry at the University of Paris-Saclay and at the ENS Paris-Saclay. He obtained his PhD in 2020 in Chemical Biology under the supervision of Dominique Urban (ICMMO) and Boris Vauzeilles (ICSN). Then, he worked with Pierre-Yves Renard and Ludovic Jean at COBRA in Rouen. In 2023, he moved to Berlin to join Sigrid Milles' group and JB's lab to work on innovative labeling strategies for high resolution spectroscopic techniques.
Kilian studied chemistry at the Julius-Maximilian-University Würzburg (JMU) with focus on Organic, Physical and Medicinal Chemistry. For his Master Thesis he joined the group of Dirk Trauner at New York University (NYU), where he worked on photoswitchable PROTACs. After graduating in 2019, Kilian decided to join JB’s lab in 2020 to work on novel imaging techniques.
Ramona studied Biology with a focus on genetics and molecular biology at the Humboldt University Berlin, graduating 2010 in Molecular Ecology. After a stint at WITA GmbH, she joined the FMP as technical assistant in 2011, working in the field Molecular Cellular Physiology and Mass Spectrometry. Enjoying nature and being a passionate hiker in her free time, she teamed up with JB in 2020 to support and pursue our quests in Chemical Biology.
The Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) is part of the Forschungsverbund Berlin e.V. (FVB), which legally represents seven non-university research institutes - members of the Leibniz Association - in Berlin.
Leibniz-Forschungsinstitut für Molekulare Pharmakologie im Forschungsverbund Berlin e.V. (FMP)
Campus Berlin-Buch
Robert-Roessle-Str. 10,
13125 Berlin, Germany
