Florian I Schmidt Laboratory


Tools for research - therapies for humans

Project details

Nanobodies are single domain antibodies derived from heavy chain-only antibodies found in camelid species. These small 15 kDa proteins bind to target molecules with affinity and specificity. Bacterially expressed nanobodies can be fluorescently labeled to visualize the target in advanced microscopy techniques, or modified with biochemical handles for protein purification. Unlike antibodies, nanobodies can also be expressed in the cytosol of living cells to visualize and perturb function of endogenous targets in living cells.

To generate nanobodies, we immunize alpacas and llamas and subsequently construct a plasmid library encoding the diversity of nanobodies generated in the animal. We then apply phage display as well as functional screens to identify suitable nanobodies. We are in the process of assembling a comprehensive collection of nanobodies targeting the major innatei mmune signaling pathways. These allow us to specifically interfere with (or activate) the distinct steps of innate immune signaling to learn mechanistic lessons.

Project-related publications

Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape

Koenig PA, Das H, Liu H, Kümmerer BM, Gohr FN, Jenster LM, Schiffelers LDJ, Tesfamariam YM, Uchima M, Wuerth JD, Gatterdam K, Ruetalo N, Christensen MH, Fandrey CI, Normann S, Tödtmann JMP, Pritzl S, Hanke L, Boos J, Yuan M, Zhu X, Schmid-Burgk JL, Kato H, Schindler M, Wilson IA, Geyer M, Ludwig KU, Hällberg BM, Wu NC, Schmidt FI.

Science. 2021 Feb 12;371(6530):eabe6230. doi: 10.1126/science.abe6230. Epub 2021 Jan 12.

Nanobody-directed targeting of optogenetic tools to study signaling in the primary cilium

Hansen JN, Kaiser F, Klausen C, Stüven B, Chong R, Bönigk W, Mick DU, Möglich A, Jurisch-Yaksi N, Schmidt FI, Wachten D.

Elife. 2020 Jun 24;9:e57907. doi: 10.7554/eLife.57907.

Vesicular stomatitis virus N protein-specific single-domain antibody fragments inhibit replication

Hanke L, Schmidt FI, Knockenhauer KE, Morin B, Whelan SP, Schwartz TU, Ploegh HL.

EMBO Rep. 2017 Jun;18(6):1027-1037. doi: 10.15252/embr.201643764. Epub 2017 Apr 10.

The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment

Hanke L, Knockenhauer KE, Brewer RC, van Diest E, Schmidt FI, Schwartz TU, Ploegh HL.

mBio. 2016 Dec 13;7(6):e01569-16. doi: 10.1128/mBio.01569-16.

Phenotypic Lentivirus Screens to Identify Antiviral Single Domain Antibodies

Schmidt FI.

Methods Mol Biol. 2018;1836:139-158. doi: 10.1007/978-1-4939-8678-1_7.

Phenotypic lentivirus screens to identify functional single domain antibodies

Schmidt FI, Hanke L, Morin B, Brewer R, Brusic V, Whelan SP, Ploegh HL.

Nat Microbiol. 2016 Jun 20;1(8):16080. doi: 10.1038/nmicrobiol.2016.80.

A single domain antibody fragment that recognizes the adaptor ASC defines the role of ASC domains in inflammasome assembly

Schmidt FI, Lu A, Chen JW, Ruan J, Tang C, Wu H, Ploegh HL.

J Exp Med. 2016 May 2;213(5):771-90. doi: 10.1084/jem.20151790. Epub 2016 Apr 11.

Exploiting Nanobodies' Singular Traits

Ingram JR, Schmidt FI, Ploegh HL.

Annu Rev Immunol. 2018 Apr 26;36:695-715. doi: 10.1146/annurev-immunol-042617-053327. Epub 2018 Feb 28.

Project-related funding

SFB 1403

Deutsche Forschungsgemeinschaft (DFG)


Deutsche Forschungsgemeinschaft (DFG)

SPP 1923

Deutsche Forschungsgemeinschaft (DFG)

Emmy Noether Programme

Deutsche Forschungsgemeinschaft (DFG)

Project-related scientists

Florian Schmidt Lab
Florian Schmidt Lab
Florian Schmidt Lab
Florian Schmidt Lab
Florian Schmidt Lab
Florian Schmidt Lab
Florian Schmidt Lab

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