Jan Steyaert

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Jan Steyaert
Jan Steyaert.jpg
NationalityBelgian
Alma materVrije Universiteit Brussels
TitleProf.

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.

Contents

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 of 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.

In 2024 he was rewarded an ERC advanced grant form the ERC council.

In 2025 he received the 2025 Christian B. Anfinsen Award, sponsored by The Protein Society, in recognition of technological achievements and significant methodological advances in the field of protein science.

References

  1. ↑ "Find people in the EMBO Communities". people.embo.org. Retrieved 2022-04-05.
  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.
  8. ↑ "Adrenaline receptor 'frozen in action' by researchers". ScienceDaily. Retrieved 2022-04-05.
  9. ↑ Sprang, Stephen R. (January 2011). "Binding the receptor at both ends". Nature. 469 (7329): 172–173. doi:10.1038/469172a. ISSN   0028-0836. PMC   3804163 . PMID   21228868.
  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.
  19. ↑ Lohse, Martin J.; Calebiro, Davide (March 2013). "Receptor signals come in waves". Nature. 495 (7442): 457–458. doi: 10.1038/nature12086 . ISSN   0028-0836. PMID   23515157. S2CID   205233676.
  20. ↑ "Xanax zonder bijwerkingen? Nieuwe uitvinding van de VUB kan het mogelijk maken". Het Laatste Nieuws (in Dutch). 2019-01-10. Retrieved 2023-11-06.
  21. ↑ Jansen, Michaela (January 2019). "An in-depth structural view of a GABAA brain receptor". Nature. 565 (7740): 436–438. Bibcode:2019Natur.565..436J. doi: 10.1038/d41586-018-07843-7 . ISSN   0028-0836. PMID   30666053. S2CID   58572372.
  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.
  24. ↑ "Prous Institute - Overton and Meyer Award for New Technologies in Drug Discovery". www.efmc.info. Retrieved 2022-04-05.
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