From Wikipedia, the free encyclopedia
Jan Steyaert
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.

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

  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.
From Wikipedia, the free encyclopedia
Jan Steyaert
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.

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

  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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