NCCR "Structural Biology - Molecular Life Sciences: Three Dimensional Structure, Folding and Interactions" (2001-2013)
NCCR Director: Prof. Markus Grütter (2001-2013)
Home Institution: University of Zurich
Research in the NCCR and major results
The NCCR “Structural Biology - Molecular Life Sciences: Three Dimensional Structure, Folding and Interactions” focused its research activities on the three key areas membrane proteins, supramolecular assemblies and development of new technologies. Much has been achieved in each area.
In the area of “membrane proteins”, the NCCR’s research focused on a specific type of so-called transporters, which are central to the function of cells since they allow or actively regulate the diffusion or movement of substances into the cell. The major highlights in this area were the elucidation of the crystal structures of many of these systems and the understanding of the mechanism of these clinically relevant channels and transporters. In the area of supramolecular assemblies, specific aspects in the systems DNA, ribosomes and protein filaments were studied. The atomic structure of the nucleosome and the chromatin fibre in the DNA was elucidated. In addition, the researchers determined the first complete structures of ribosomal subunits in more highly developed cells. Finally, research in the NCCR generated some basic insights into so-called filaments of bacteria that are critical for bacterial virulence as they allow a better interlinkage to certain surfaces.
The technology developed by the NCCR was based on an extensive set of methods from protein engineering, structure determination technologies (such as x-ray, nuclear magnetic resonance imaging (NMR) and electron microscopy) as well as single molecule spectroscopy and computational approaches.
The SNSF awarded this NCCR roughly CHF 37 million for a duration of 12 years of research. The table below shows that SNFS funding represented 30% of the overall expenditure of the NCCR. The remaining funds consisted of contributions from the home institutions and from third parties as well as funds contributed by the research groups themselves.
Finanzierung 2001 - 2013
Period Funding sources(CHF) 2001 - 2004 2005 - 2008 2009 - 2012 2001 - 2013 % SNSF funding 13'211'311 13'837'122 9'600'037 36'648'470 29.8 Self-funding by University of Zurich 4'983'971 6'292'339 5'596'468 16'872'778 13.7 Self-funding by ETH Zurich 3'975'896 3'925'116 2'689'985 10'590'997 8.6 Self-funding by project participants 16'290'549 18'980'013 22'508'928 57'779'490 47.0 Third-party funding 50'000 723'630 264'508 1'038'138 0.8 Total 38'511'727 43'758'220 40'659'926 122'929'873 100.0
International standing of Swiss research
The Review Panel mandated by the SNSF to evaluate this NCCR was enthusiastic in its final assessment: "the group must be regarded as the leading consortium of structural biologists in the international realm." The outstanding scientific output of the NCCR resulted in the publication of more than 600 articles, including 25 articles in the most prestigious scientific journals (such as Nature, Science).
The NCCR participants are leading experts in their research fields. This is borne out by the numerous prizes and honorary memberships awarded to the NCCR participants have been awarded. Foremost among these is the Nobel Prize in chemistry awarded to Kurt Wüthrich in 2002. Five NCCR members are grantees of the European Research Council. Indeed, the exceptional international standing of structural biology research in Zurich attracted a number of brilliant young scientists, who were all recruited to higher academic posts and subsequently obtained permanent professorships.
Type Number Peer-reviewed articles 674 Articles without peer review 39 Articles in anthologies 13 Books 25 Reports 0 Total 751
Structural development – Perspectives for the research domain
The NCCR together with the ETHZ and the University of Zurich secured favourable organisational conditions for structural biology in Zurich to ensure Switzerland's position at the forefront of this field in the coming years. The newly established "Zurich Centre for Molecular Structure and Mechanism" (ZCMSM) has come to play a key role in maintaining this leading position. The SwissFEL (Switzerland's X-ray free-electron laser at PSI) opens up new possibilities for crystallography research. The discoveries that lie ahead are likely to change our understanding of the molecular life sciences, and society will benefit in the best tradition of scientific endeavour.
Structural measures Number of created professorships
- 3 new full professors
- 3 new assistant professors
- 3 replacements (i.e. retired professors replaced by professors participating in NCCR)
Junior group leaders
- The NCCR did not appoint any junior group leaders.
Infrastructure / platforms
- High throughput crystallisation platform, University of Zurich (UZH) and ETH Zurich (ETHZ)
- High throughput protein expression and ribosome display platform, UZH
- Isotope labelling platform, ETHZ
- Center for Cell Imaging and NanoAnalytics C-CINA, Biozentrum, D-BSSE, Basel (with financial contributions from the NCCR)
- Specific Beamline at Swiss Light Source SLS, PSI, Villingen (with financial contributions from the NCCR)
- University of Zurich, ETH Zurich, M.E. Müller Institute University of Basel; Paul Scherrer Institute, EPF Lausanne
- University of Applied Science Basel, F. Hoffmann Roche AG, Novartis AG, Actelion Pharmaceuticals, Boehringer-Ingelheim, Molecular Partners, Novo Nordisk, Polyphor
- Protein Production Platform P-CUBE a EU research infrastructure project, European Membrane Biology Network EMBN
Knowledge and technology transfer to society and industry
The NCCR participants applied for 34 patents, of which several were licensed out for non-exclusive use or production. Research carried out by NCCR groups resulted in the founding of two spin-off companies, both of which are still operating and continuing to grow. Molecular Partners AG is a spin-off of the University of Zurich that exploits the patented ankyrin technology. In operation since 2005, the company headcount has grown to 70 full-time employees (2013). Following successful clinical trials, a multimillion USD exclusive license agreement was signed in 2011 with the healthcare company Allergan for a specific inhibitor for ophthalmic indications. Redbiotec, a spin-off of ETH Zurich, was founded in 2006. The company commercially exploits the patented "Multibac" system for the expression of multiprotein assemblies. One application of this technology is the development of next generation antiviral vaccines.
Knowledge and technology transfer
Type Number Filed patents 34 Licences 17 Start-up companies 2 Prototypes, demonstrators - Processes, products 2 CTI projects 2
After completing their studies, 22% of the doctoral students and postdocs found jobs in the private or public sector. These young researchers play a key role in direct knowledge transfer between the public and the private sector.
Promotion of young scientists and the academic careers of women
NCCR Structural Biology provided practical and theoretical training of high quality to its own students and to young scientists from other institutions. The annual symposia on structural biology attracted high-profile international speakers and promising young scientists and regularly provided a platform for personal interaction with leaders in the field.
A particular advantage of the PhD programme "Biomolecular Structure and Mechanism" was the possibility of contributing to one of the long-term NCCR projects, along with the opportunity of being exposed to most of the modern technologies in structural biology. Interdisciplinary collaboration between NCCR groups was an additional asset from which PhD students and post-docs strongly benefited. Of the 33 alumni who had established independent research groups by the end of the NCCR, five were women and two were grantees of the European Research Council.
Gender equality is still a distant goal in the natural sciences in Switzerland. Nonetheless, some progress has been made in the field of structural biology: the share of female postdoctoral fellows and PhD students was steady at about 25-35% of the entire group of junior scientists.