People in and around VIB are well aware of our adage: basic research as a starting point for tangible solutions that benefit society. But translating a paper or a technology into a groundbreaking new drug or agricultural application doesn’t happen overnight. The importance of the tech transfer process was recently illustrated by a study led by Nico Callewaert (VIB-UGent) and Jan Steyaert (VIB-VUB). The paper presents a technology platform for synthetic biology, and is a great example of how innovation and entrepreneurship go hand in hand.
The study Modular Integrated Secretory System Engineering In Pichia pastoris To Enhance G-Protein Coupled Receptor Expression, conducted in the VIB labs of Nico Callewaert and Jan Steyaert was published in the May issue of ACS Synthetic Biology (see box). It is the second VIB paper that concerns the complex field of membrane protein expression technology.
Nico, can you describe the research in a nutshell?
Nico: “We provide a technology package that integrates four engineering modules in the yeast Pichia pastoris. Our goal was to increase the expression of membrane proteins to quantities that allow studies and screenings, and, ultimately, drug development. We used the human G-protein-coupled receptors – also known as GPCRs – as examples of these proteins. Located on the surfaces of cells, these molecules receive chemical signals and pass them on. Because these GPCRs play an essential part in a wide variety of processes and diseases, they are attractive drug targets.”
Impact through expertise
The research is a prime example of one of our cornerstones: cross-departmental collaboration. The joint effort of Nico’s Medical Biotechnology Center and Jan’s Structural Biology Research Center has established VIB even more firmly in the global biotechnology firmament. The second typical VIB feature is, as mentioned, the clear tech transfer component, which funnels the findings into the next phase: the development of new medical solutions.
Jan: “This publication describes yet another application of our expanding Nanobody®-enabled platform for the stabilization of difficult to handle proteins including membrane proteins, amyloidogenic proteins and protein complexes. Together with Brian Kobilka (Stanford University), we applied similar methods to stabilize and elucidate the first active signaling structures of GPCRs. These results were conductive in awarding the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilka. Last year, VIB and VUB created Confo Therapeutics, a spin-off that builds on the same technology to allow easier investigation of GPCRs, which can be a tremendous advantage for drug discovery.”
One study, two sequels
Bridging the gap between research and the market is an important aspect of the job of Carla Snoeck, Manager New Ventures at VIB. She points out that basic research is more than a crucial threshold for follow-up studies, as generally assumed – it can also immediately serve as the basis for innovative products and technologies with huge impact.
Carla: “As Jan and Nico are both basic researchers, they conduct the kind of science that doesn’t always immediately lead to concrete applications. But they develop so-called ‘enabling’ technologies that are instrumental to elucidate novel targets and underlying biological mechanisms – which is, after all, our core business. In addition, these platform technologies can be applied in numerous domains. That gives them huge societal and economic relevance.”
Can you describe some possible applications of Jan and Nico’s study?
Carla: “They are developing generic technologies that enable the structural and functional characterization of proteins that are notoriously difficult to purify and to study with any available method today, hereby focusing on the highest hanging fruits. The combination of solid scientific data and external validation by academia and industry emphasizes the uniqueness of these technologies and its broad application potential in different fields. The current study can for example be used to tackle bottlenecks in drug discovery and product development trajectories. The best proof are the ongoing collaborative partnerships and spin-offs in the pipeline.”
Claes et al., ACS Synthetic Biology 2016