Project (Dirk Görlich - Johannes Söding)
Bioinformatics-supported deep Nanobody discovery
Nanobodies are very powerful tools for immunofluorescence, super-resolution microscopy, as crystallization chaperones, or for therapeutic neutralization of pathogens. They correspond to the antigen-binding domains of camelid heavy chain-only antibodies. They can be selected by phage display, e.g. from alpaca immune libraries, and are easily produced in microorganisms such as E. coli or yeast.
The project aims to develop a deep discovery workflow for nanobodies that integrates powerful selection strategies with deep sequencing and AI-based sequence analysis. It will be a highly interdisciplinary project combining wet lab work and bioinformatics. Once established, the workflow will be applied to target highly complex antigens, for example, to develop new therapies for cancer and infectious diseases.
Homepage Research Group
https://www.mpinat.mpg.de/goerlichPublications:
Chug H, Trakhanov S, Hülsmann BB, Pleiner T, Görlich D (2015) Crystal structure of the metazoan Nup62•Nup58•Nup54 nucleoporin complex. Science, 350: 106–110. doi: 10.1126/science.aac7420
Pleiner T, Bates M, Trakhanov S, Lee CT, Schliep JE, Chug H, Böhning M, Stark H, Urlaub H, Görlich D (2015) Nanobodies: site-specific labeling for super-resolution imaging, rapid epitope-mapping and native protein complex isolation. Elife, 4: e11349. doi: 10.7554/eLife.11349
Pleiner T, Bates M, Görlich D (2018) A toolbox of anti-mouse and anti-rabbit IgG secondary nanobodies. J Cell Biol, 217: 1143–1154. doi: 10.1083/jcb.201709115
Güttler T, Aksu M, Dickmanns A, Stegmann KM, Gregor K, Rees R, Taxer W, Rymarenko O, Schünemann J, Dienemann C, Gunkel P, Mussil B, Krull J, Teichmann U, Groß U, Cordes VC, Dobbelstein M, Görlich D (2021) Neutralization of SARS-CoV-2 by highly potent, hyperthermostable, and mutation-tolerant nanobodies. EMBO J, e107985. doi: 10.15252/embj.2021107985
Loreau V, Rees R, Chan EH, Taxer W, Gregor K, Mußil B, Pitaval C, Luis NM, Mangeol P, Schnorrer F, Görlich D (2023) A nanobody toolbox to investigate localisation and dynamics of Drosophila titins and other key sarcomeric proteins. Elife, 12: e79343. doi: 10.7554/eLife.79343
Solà Colom M, Fu Z, Güttler T, Trakhanov S, Srinivasan V, Gregor K, Pleiner T, Görlich D (2023) Nucleoporin-binding nanobodies that either track or inhibit nuclear pore complex assembly. bioRxiv, doi: 10.1101/2023.09.12.557426