Technology platforms are becoming increasingly important as an integral part of research institutions. This is not only because of efficiency and cost optimization. As centralized shared resources with specific scientific competence and customized services, technology platforms provide researchers with easy access to instrumentation, technology and expert know-how.
Staff personnel are highly trained individuals – some with decades of professional experience – who are keeping up with the exponential growth of technological advances in order to meet the evolving requirements of the scientific community.
The NCCR RNA & Disease offers its research members the unique opportunity to make use of state-of-the-art technology platforms for crystallization, next-generation sequencing, nuclear magnetic resonance, proteomics, and RNA synthesis, and this mostly free of charge. Some platforms ask for a service fee, which however, is the same as for in-house researchers. Most platforms offer specific trainings to NCCR members on a case-by-case basis and hold regular seminars.
The above mentioned technology platforms provide NCCR researchers with facilities and support at no or very little costs including full confidentiality of project and analysis results. This way, they are central in creating a competitive research environment and contribute significantly to the scientific advancement of the projects within the NCCR RNA & Disease. It is therefore important that their contribution is adequately recognized.
Whether this will be an acknowledgement or a co-authorship depends on the individual project and on the contribution made by the platform personnel. As a rule of thumb: staff personnel who make substantial intellectual and/or experimental contributions should be credited as co-authors. Platform operators are scientists and, as for any researcher, a proper acknowledgment in publications is an important metric of the value of their platform.
Find the five NCCR platforms briefly presented on the following page.
The Crystallization Platform of Nenad Ban’s research group at the Institute of Molecular Biology & Biophysics, ETH Zürich, Hönggerberg, has been established with the aim to enhance success rate and speed of the structure determination process by X-ray crystallography. The platform performs automated high throughput biomolecule crystallization screens by means of low-volume crystallization and liquid handling robotics. The infrastructure portfolio includes commercial and customized screens, libraries of stock solutions, and a manually operated crystallization setup. Additionally, NCCR members benefit from the service and expert knowledge on sample preparation, and may enjoy individual training on how to set up crystallization screens and visually inspect crystals. Around 1’000 different initial crystallization conditions can be covered in a first screen. The platform is also equipped to handle biomolecules that need special requirements such as membrane proteins, RNA and RNA-protein complexes. The service is free of charge and there is no collaborative claim upon crystallization success. However, the Ban lab is open to discuss a possible collaboration in structure determination in the case a NCCR researcher is able to reproducibly grow suitable crystals.
Next Generation Sequencing
The Next Generation Sequencing (NGS) Platform of the University of Bern provides researchers of the NCCR access to a variety of nucleic acid sequencing methodologies, and assistance with design and data analysis of genome-wide experiments. The platform is equipped with different powerful ultra-high-throughput sequencers for largescale genomics and for more focused applications. With the new illumina HiSeq3000, the NGS service currently has the fastest sequencing instrument in Switzerland. The platform strives to accommodate flexible experimental designs requiring between a few Mb up to several Tb of raw data. In addition, it provides a wide range of accessory instruments for sample and library preparations. The core facility personnel is willing to offer user training for groups who would like to perform their own NGS experiments. Services are offered to NCCR researchers on the basis of internal user fees. First-time users are strongly encouraged to check and discuss the experiment(s) with Tosso Leeb, the director of the NGS platform, before submitting samples. Although commercial sequencing suppliers can provide very good services, most experiments can be done at lower prices and with much more reciprocal understanding of scientific and technological details at the NGS platform.
Mass Spectrometry and Proteomics
The Mass Spectrometry and Proteomics Core Facility (PMSCF) at the Department of Clinical Research, University of Bern, offers Liquid Chromatography Mass Spectrometry (LC-MS) instrumentation, technical support and methodological assistance for the identification and characterization of single proteins, as well as for proteome quantification for applications within proteomics, biopharma and metabolomics. The service covers techniques used in sample preparation for LC-MS, protein identification and fractionation of complex protein mixtures, analyses of phosphopetides and other post-translational modifications, peptide sequencing, and provides methods for the (semi-)quantitative estimation of protein abundances. Equipped with the latest Orbitrap technology, it is also possible to measure the mass of intact proteins as large as 150 kDa. The PMSCF group headed by Manfred Heller comprises four researchers and is located in the Kinderklinik at the Inselspital, Bern.
NCCR researchers pay the same service fees as researchers at the University of Bern. The PMSCF stands out due to high flexibility and welcomes to discuss and plan new projects carefully beforehand with the service users.
Biomolecular NMR Spectroscopy
The Biomolecular NMR Spectroscopy Platform (BNSP) of the Department of Biology at the ETH Zürich, Hönggerberg, offers state-of-the- art know-how and infrastructure for the study of biomolecules in solution. The platform operates six NMR spectrometers with magnetic field strengths ranging from 500 to 900 MHz, and provides expertise and support on the production of isotopically labeled samples, NMR experiment set-ups, data analysis, and structure calculations. In addition to the NMR instruments, a new machine that uses the SwitchSense technology is available, which allows to measure the motion of biomolecules on a chip and to capture ultra-fast and ultra-slow kinetics. Kd-values can be measured from the fM to mM range by using low concentrations of unlabeled molecules. This approach can be used to measure differences in affinity between WT and mutated versions of protein-RNA complexes and can be extended to the study of protein-DNA, protein-protein and protein-small molecule interactions. The platform provides researchers who are adequately trained in NMR spectroscopy with operation time and offers to scientists who do not have or wish training a basis for potential collaboration. NCCR researchers have direct access through Antoine Cléry, who is the BNSP scientific adviser for the members of the NCCR RNA and Disease. There is no fee, and the costs of the NMR isotopes used for protein labeling are borne by the NCCR. The platform prefers collaborative short-termed projects such as experiments on biomolecular interactions, but is also interested in long- term experiments such as macromolecular structure elucidation.
The RNA Synthesis Platform of the Institute of Pharmaceutical Sciences, ETH Zürich, Hönggerberg, run by senior scientist Ugo Pradère in the lab of Jonathan Hall provides NCCR members access to a broad expertise in the synthesis of various types of oligonucleotides (DNAs, RNAs, 2’-modified) including a wide range of chemical modifications. The platform is equipped with two automated MerMade DNA/RNA synthesizers, which perform oligonucleotide synthesis according to the state-of-the-art solid-phase phosphoramidite method. RNAs and DNAs with lengths up to 80 and 140 nucleotides can be synthesized with modifications incorporated sequence-specifically. One aim of the platform is to provide non-commercially available oligonucleotides as key tools for biological research. Preparative high-performance liquid chromatography (HPLC) meets the needs for yield and purity of the synthesized oligonucleotides. Modified oligonucleotides are delivered in a scale ranging from 1 nmol to 0.5 µmol, quantities that are suited for biochemical, biological and structural studies. Delivery of milligram quantities is also feasible. NCCR researchers have access to free technical services and expert knowledge funded by the NCCR. Currently, the platform has a dozen of ongoing projects with NCCR members and other research groups. Any researcher with a need for specific oligonucleotide structures is encouraged to contact the head of the platform.
By Thomas Schnyder