A novel fluorescent S1P-receptor ligand (top) marks specific leukocytes in the thymus, lymph node and Peyer's patches in the gut of mice (bottom). The bottom panels show 2-photon images of explanted organs (Kiefer and Haufe groups).
© CiM

A.5: Surface-Targeted Tracking of Individual Cells In Vivo

Participants: Günter Haufe, Johannes Eble, Ryan Gilmour, Rupert Hallmann, Uwe Karst, Friedemann Kiefer, Klaus Langer, Henning Mootz, Andrea Rentmeister, Cristian A. Strassert, Mark Waller, Bernhard Wünsch

Most currently used approaches to monitor the mobility of live cells rely on genetics for the introduction of a fluorescent tag or marker molecule into defined proteins or cell populations and subsequent imaging. Alternative strategies utilize the non-invasive introduction of reporter molecules but require the development of probes that are highly specific for a particular cell population or cellular state. CiM researchers have succeeded in generating several of such reporters, for example low molecular weight non-peptide MMP probes, RGD-based integrin specific probes, isatin-based caspase ligands and chemokine receptor ligands that have been successfully employed for FRI and PET imaging in vivo. In A.5 this probe development will be extended to new molecular targets identified in other research projects as being specific for a population of cells or a cellular process (e.g. stem and germ cell migration/differentiation, leukocyte extravasation). The novel ligands will be chemically engineered and labelled with fluorescent or radioactive moieties, and their biological, pharmacokinetic and metabolic properties will be determined. As a primary example for the development of necessary core technologies and future targeting strategies we will develop tracers for the specific in vivo labelling of highly motile macrophages that are the focus of many other research projects. Central to A.5 is the development of selective and reliable techniques for the chemical synthesis of biologically active tracers and the efficient and specific labelling of cellular processes and cells in vivo. This will contribute to the in vivo analysis of pathological and regenerative processes and will be essential for the establishment of novel imaging-based regimes for diagnosis and treatment in patients.

Funded Projects

FF-2017-07 – Tunneling nanotubes and mitochondria: Intracellular interactions and intercellular trafficking investigated with new intein-based techniques
Principal investigators: Karin Busch, Henning Mootz
Project time: 11/2017 - 12/2018

FF-2016-09 – A chemo-enzymatic approach for posttranscriptional RNA-labeling in living zebrafish
Principal investigators: Sebastian Leidel, Andrea Rentmeister
Project time: 07/2016 - 10/2018

FF-2016-13 – Novel tools for mRNA labeling in Drosophila
Principal investigators: Sebastian Rumpf, Andrea Rentmeister
Project time: 07/2016 - 10/2018

FF-2013-17 – Studying Cells in Motion by Complementary Magnetic Resonance and Mass Spectrometric Imaging
Principal investigators: Uwe Karst, Cornelius Faber
Project time: 07/2013 - 06/2015
 
FF-2013-28 – Development of novel, dual purpose, MOBSAM-based, specific inhibitors for MMP-2/9 to image and investigate their activity in inflammatory pathologies in vivo
Principal investigators: Lydia Sorokin, Günter Haufe
Project time: 07/2013 - 06/2015