Jan Steyaert

Jan Steyaert is a Belgian bioengineer and molecular biologist. He started his career as an enzymologist but the Steyaertlab is best known for pioneering work on (engineered) nanobodies for applications in structural biology, omics and drug design. He is full professor and teaches biochemistry at the Vrije Universiteit Brussel and Director of the VIB-VUB Center for Structural Biology, one of the Research Centers of the Vlaams Instituut voor Biotechnologie (VIB). He was involved in the foundation of three spin-off companies: Ablynx, Biotalys, and Confo Therapeutics.

Jan Steyaert
NationalityBelgian
Alma materVrije Universiteit Brussels
TitleProf.

Early life and education

Steyaert was born in Ukkel, Belgium. He grew up in the Flemish village of Alsemberg. He obtained a Master in Bioengineering at the Vrije Universiteit Brussel. For his PhD, he moved to Plant Genetic Systems, one the very first biotech companies in Belgium. After obtaining his Ph.D., he relocated to Kenya to perform postdoctoral research at ILRAD (now ILRI), the International Livestock Research Institute.

Academic career

In 1995, he returned to Belgium to become assistant professor in the Structural Biology Laboratory of Lode Wyns.  

From 2015 to 2017, he was a Francqui Research Professor.

In 2020, he was elected as a member of the European Molecular Biology Organization.[1]

Research

Jan Steyaert pioneered the use of nanobodies as tools in structural biology. Nanobodies are the variable domains of heavy-chain only antibodies that naturally occur in camelids. Because of their small size and their beneficial biochemical and economic properties (size, affinity, specificity, stability, production cost), Steyaert applies nanobodies to freeze dynamic proteins into single functional conformations. X-ray crystallography or cryogenic electron microscopy can then be used to determine the structures of different stills of the same moving biomolecule.[2][3][4]

In collaboration with Brian Kobilka the research team of Steyaert generated nanobodies[5][6] elucidate the crystal structure of several G-protein-coupled receptors (GPCR), including the ß2 adrenergic receptor,[7][8][9] the muscarinic acetylcholine receptor,[10][11] the μ-opioid receptor,[12][13] the metabotropic glutamate receptors[14][15] and, as a first, the crystal structure of a GPCR-G protein complex.[16][17]

Steyaert also applies nanobodies as versatile tools for investigating GPCR dynamics in vitro and inside cells,[18][19] and for improved drug discovery.[20][21][22][23] More recently, he started engineering Nanobodies for applications in cryo-EM.

Awards

In 2016 he received The Prous Institute-Overton and Meyer Award for New Technologies in Drug Discovery[24] for his pioneering work in the field of nanobody-enabled structural biology.

From 2019 onwards, Jan Steyaert is a Web of Science Highly Cited Researcher in the field of Biology and Biochemistry.

In 2022 he won the Brandeis’ 24th Jacob and Louise Gabbay Award in Biotechnology and Medicine in recognition of his contributions to structural biology through the development of Camelid single-domain antibodies or nanobodies.

References
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  2. Uchański, Tomasz; Masiulis, Simonas; Fischer, Baptiste; Kalichuk, Valentina; López-Sánchez, Uriel; Zarkadas, Eleftherios; Weckener, Miriam; Sente, Andrija; Ward, Philip; Wohlkönig, Alexandre; Zögg, Thomas (January 2021). "Megabodies expand the nanobody toolkit for protein structure determination by single-particle cryo-EM". Nature Methods. 18 (1): 60–68. doi:10.1038/s41592-020-01001-6. ISSN 1548-7091. PMC 7611088. PMID 33408403.
  3. Uchański, Tomasz; Pardon, Els; Steyaert, Jan (February 2020). "Nanobodies to study protein conformational states". Current Opinion in Structural Biology. 60: 117–123. doi:10.1016/j.sbi.2020.01.003. PMID 32036243. S2CID 211070876.
  4. Setyawati, Inda; Stanek, Weronika K; Majsnerowska, Maria; Swier, Lotteke J Y M; Pardon, Els; Steyaert, Jan; Guskov, Albert; Slotboom, Dirk J (2020-12-22). "In vitro reconstitution of dynamically interacting integral membrane subunits of energy-coupling factor transporters". eLife. 9: e64389. doi:10.7554/eLife.64389. ISSN 2050-084X. PMC 7755397. PMID 33350937.
  5. Steyaert, Jan; Kobilka, Brian K (August 2011). "Nanobody stabilization of G protein-coupled receptor conformational states". Current Opinion in Structural Biology. 21 (4): 567–572. doi:10.1016/j.sbi.2011.06.011. PMC 3166880. PMID 21782416.
  6. Manglik, Aashish; Kobilka, Brian K.; Steyaert, Jan (2017-01-06). "Nanobodies to Study G Protein–Coupled Receptor Structure and Function". Annual Review of Pharmacology and Toxicology. 57 (1): 19–37. doi:10.1146/annurev-pharmtox-010716-104710. ISSN 0362-1642. PMC 5500200. PMID 27959623.
  7. Rasmussen, Søren G. F.; Choi, Hee-Jung; Fung, Juan Jose; Pardon, Els; Casarosa, Paola; Chae, Pil Seok; DeVree, Brian T.; Rosenbaum, Daniel M.; Thian, Foon Sun; Kobilka, Tong Sun; Schnapp, Andreas (January 2011). "Structure of a nanobody-stabilized active state of the β2 adrenoceptor". Nature. 469 (7329): 175–180. Bibcode:2011Natur.469..175R. doi:10.1038/nature09648. ISSN 0028-0836. PMC 3058308. PMID 21228869.
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  10. Kruse, Andrew C.; Ring, Aaron M.; Manglik, Aashish; Hu, Jianxin; Hu, Kelly; Eitel, Katrin; Hübner, Harald; Pardon, Els; Valant, Celine; Sexton, Patrick M.; Christopoulos, Arthur (2013-12-05). "Activation and allosteric modulation of a muscarinic acetylcholine receptor". Nature. 504 (7478): 101–106. Bibcode:2013Natur.504..101K. doi:10.1038/nature12735. ISSN 0028-0836. PMC 4020789. PMID 24256733.
  11. Gregory, Karen J. (February 2019). "How an activation signal is transmitted through an excitatory receptor". Nature. 566 (7742): 42–43. Bibcode:2019Natur.566...42G. doi:10.1038/d41586-018-07885-x. ISSN 0028-0836. PMID 30710123. S2CID 59528212.
  12. Sounier, Rémy; Mas, Camille; Steyaert, Jan; Laeremans, Toon; Manglik, Aashish; Huang, Weijiao; Kobilka, Brian K.; Déméné, Héléne; Granier, Sébastien (August 2015). "Propagation of conformational changes during μ-opioid receptor activation". Nature. 524 (7565): 375–378. Bibcode:2015Natur.524..375S. doi:10.1038/nature14680. ISSN 0028-0836. PMC 4820006. PMID 26245377.
  13. Huang, Weijiao; Manglik, Aashish; Venkatakrishnan, A. J.; Laeremans, Toon; Feinberg, Evan N.; Sanborn, Adrian L.; Kato, Hideaki E.; Livingston, Kathryn E.; Thorsen, Thor S.; Kling, Ralf C.; Granier, Sébastien (August 2015). "Structural insights into µ-opioid receptor activation". Nature. 524 (7565): 315–321. Bibcode:2015Natur.524..315H. doi:10.1038/nature14886. ISSN 0028-0836. PMC 4639397. PMID 26245379.
  14. Koehl, Antoine; Hu, Hongli; Feng, Dan; Sun, Bingfa; Zhang, Yan; Robertson, Michael J.; Chu, Matthew; Kobilka, Tong Sun; Laeremans, Toon; Steyaert, Jan; Tarrasch, Jeffrey (February 2019). "Structural insights into the activation of metabotropic glutamate receptors". Nature. 566 (7742): 79–84. Bibcode:2019Natur.566...79K. doi:10.1038/s41586-019-0881-4. ISSN 0028-0836. PMC 6709600. PMID 30675062.
  15. Gregory, Karen J. (February 2019). "How an activation signal is transmitted through an excitatory receptor". Nature. 566 (7742): 42–43. Bibcode:2019Natur.566...42G. doi:10.1038/d41586-018-07885-x. ISSN 0028-0836. PMID 30710123. S2CID 59528212.
  16. Rasmussen, Søren G. F.; DeVree, Brian T.; Zou, Yaozhong; Kruse, Andrew C.; Chung, Ka Young; Kobilka, Tong Sun; Thian, Foon Sun; Chae, Pil Seok; Pardon, Els; Calinski, Diane; Mathiesen, Jesper M. (2011-09-29). "Crystal structure of the β2 adrenergic receptor–Gs protein complex". Nature. 477 (7366): 549–555. Bibcode:2011Natur.477..549R. doi:10.1038/nature10361. ISSN 0028-0836. PMC 3184188. PMID 21772288.
  17. Schwartz, Thue W.; Sakmar, Thomas P. (September 2011). "Snapshot of a signalling complex". Nature. 477 (7366): 540–541. doi:10.1038/477540a. ISSN 0028-0836. PMID 21956322. S2CID 1059348.
  18. Irannejad, Roshanak; Tomshine, Jin C.; Tomshine, Jon R.; Chevalier, Michael; Mahoney, Jacob P.; Steyaert, Jan; Rasmussen, Søren G. F.; Sunahara, Roger K.; El-Samad, Hana; Huang, Bo; von Zastrow, Mark (March 2013). "Conformational biosensors reveal GPCR signalling from endosomes". Nature. 495 (7442): 534–538. Bibcode:2013Natur.495..534I. doi:10.1038/nature12000. ISSN 0028-0836. PMC 3835555. PMID 23515162.
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  22. Masiulis, Simonas; Desai, Rooma; Uchański, Tomasz; Serna Martin, Itziar; Laverty, Duncan; Karia, Dimple; Malinauskas, Tomas; Zivanov, Jasenko; Pardon, Els; Kotecha, Abhay; Steyaert, Jan (January 2019). "GABAA receptor signalling mechanisms revealed by structural pharmacology". Nature. 565 (7740): 454–459. Bibcode:2019Natur.565..454M. doi:10.1038/s41586-018-0832-5. ISSN 0028-0836. PMC 6370056. PMID 30602790.
  23. Pardon, Els; Betti, Cecilia; Laeremans, Toon; Chevillard, Florent; Guillemyn, Karel; Kolb, Peter; Ballet, Steven; Steyaert, Jan (2018-05-04). "Nanobody-Enabled Reverse Pharmacology on G-Protein-Coupled Receptors". Angewandte Chemie International Edition. 57 (19): 5292–5295. doi:10.1002/anie.201712581. PMID 29469969.
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