Published research by the Steyaert lab established that the small and rigid recombinant antigen binding fragments (15kDa) of Camelid heavy-chain-only antibodies - known as Nanobodies - constitute unique research tools in structural biology.
New technologies, tools, and approaches, often spanning several disciplines, are revolutionising biology and providing unprecedented opportunities to advance the frontiers of bioscience knowledge. Fascinated by the power of new technologies on the progress of science, Jan Steyaert focusses on the development of a generic molecular toolbox to study the conformational changes in proteins. We knew that many proteins are flexible and that their function is tightly connected to conformational changes but for many years, these different conformations were intractable for structure determination by any general method.
‘Freezing’ proteins to study their structure
The Steyaert lab pioneered the use of Nanobodies as exquisite tools to freeze dynamic proteins into single functional conformations. Nanobodies are the variable domains of heavy-chain only antibodies that naturally occur in camelids. X-ray crystallography or single particle cryo-EM can then be used to determine the structures of different stills of the same moving biomolecule. The power of this approach compares to the series of photographs that Eadweard Muybridge made in 1878 to uncover if a horse that trots or gallops does ever become fully airborne.
Expanding the Nanobodies’ utility
Jan Steyaert discovered nanobodies to study the dynamics of the highest hanging fruits in structural biology including amyloidogenic proteins, membrane proteins and transient multiprotein complexes. And he is expanding the utility of such conformational Nanobodies for integrative structural biology. Conformational Nanobodies can be introduced inside living cells (Intrabodies) as conformational biosensors. His lab uses protein engineering to make such Nanobodies amenable to single particle cryo-EM (Megabodies). The Steyaert lab also extensively explored the benefit of locking targets in drugable conformations for better-focused drug discovery (Confobodies).
Most of this work is performed in collaboration with top scientists worldwide, aiming to validate his toolbox on their most challenging projects. Jan Steyaert also (co)founded 3 companies (Ablynx, Agrosavfe and Confo Therapeutics), providing a living example of how basic research can be translated into value for the society.
To showcase the world-class scientific research of the Jan Steyaert Lab, you can discover their scientific papers in more detail.
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The Jan Steyaert Lab can only thrive thanks to the dedication and commitment of its people, no matter what their function or seniority.
To stay up to date in rapidly developing fields, scientists regularly interact with (international) colleagues. Conferences and other (scientific) events are an excellent way to facilitate such a continent-spanning knowledge exchange.