Project Details
Projekt
PZ – Nanobodies for multilevel examination of SLC26 transporters
Applicant
Professor Dr. Eric Geertsma
Subject Area
Anatomy and Physiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426950122
Antibodies are indispensable reagents for the detection and manipulation of proteins. Ideal antibodies with the necessary specificity and affinity for SLC26 transporters are hardly available so far. The lack of high-quality antibodies is typical for many membrane proteins, mainly due to their lack of stability, inaccessible membrane environment and small size, and thus limited availability of epitopes for conventional antibodies. For membrane proteins such as the SLC26 transporters, the so-called 'nanobodies' represent a promising and already successfully tested alternative to conventional antibodies. Nanobodies consist of the variable domain of individual, monomeric antibodies from camelids, which can be produced heterologously in E. coli. Despite their small size, they have complete antigen-binding functionality. Due to their particularly long hypervariable loop, nanobodies can also bind in protein cavities that are inaccessible to conventional antibodies, such as the substrate binding cleft of SLC26 transporters. This enables nanobodies to conformationally arrest and inhibit transport proteins. They are therefore ideally suited for the functional and structural analysis of these proteins and have a high potential for therapeutic applications. In addition, their small size leads to better tissue accessibility compared to conventional antibodies. We will generate nanobodies against all membrane transport proteins investigated in this research group and subject them to stringent quality control to test their specificity and applicability. The special ability to bind transport proteins and the diversity of their applications make nanobodies ideal tools for the entire work programme of this research group - from structure elucidation to the isolation of protein complexes and the visualization of subcellular localization in tissue. In perspective, they are suitable for the future development of SLC26-targeted therapeutics.
DFG Programme
Research Units
