Biophysics, Structural Biology and Screening (BiSS)

Characterization and enzymology

• Zetasizer Nano ZS (Malvern Panalytical), DLS
• J-810 Spectropolarimeter (Jasco), CD
• MiniDAWN^® TREOS^® (Wyatt Technology) - RefractoMax520 - Prominence-i LC-2030C 3D (Shimadzu), SEC-MALS 
• MicroCal iTC200 (GE Healthcare), ITC 

Ligand screening

• Mosquito^® HV (ttplabtech), Mosquito HV 
• TECAN Spark^® 20M (Bergman), TECAN 
• CreoptixWave, GCI 

Crystallography 

• Mosquito^® LCP (ttplabtech) 
• ROCK IMAGER 182 (Formulatrix^®) 

Structural biology

• MFP-3D-BIO^TM (Asylum Research), AFM 
• Vitrobot MkIV (Thermo Scientific), Cryo EM preparation

To understand biomolecular function, as well as to be able to carry out structure-based experiments and drug design, it is mandatory to obtain high-resolution 3D structural information on the molecular system. BiSS carries significant expertise in protein X-ray crystallography and other structural biology techniques.

Macromolecular crystallization

The BiSS laboratory is well equipped with state-of-the-art equipment for high-throughput screening of crystallization conditions. The Mosquito LCP robot allows to set up nanoliter-scale crystallization experiments rapidly for both soluble and membrane proteins.

An automated imaging system for crystallization plates is available, which can be used for imaging with both visible and UV light. Images are centrally stored and can be accessed from an external computer. 

A number of microscopes, including a UV light source, and programmable incubators are also available for more manual screening and optimization. All necessary tools exist for preparing and transporting crystals to synchrotrons for high-resolution data collection. 

The crystallization laboratory is part of the NORCRYST national infrastructure network. 

Crystal testing and data collection

An X-ray diffractometer, also funded through NORCRYST, for crystal testing and data collection has been installed and will be in operation soon.

Crystallographic data collection is routinely carried out at various large European synchrotron infrastructures. The structural biology community at UiB has common block allocation group (BAG) beamtime at the DESY (Germany) and Diamond (UK) synchrotron light sources. In addition, a Norwegian national BAG operates at ESRF (France). Beamtime is frequently available for both X-ray crystallography and small-angle X-ray scattering (SAXS). 

Synchrotron data collection and structure determination are available on a case-by-case collaborative basis, depending on resources. 

Users interested in macromolecular crystallization at BiSS, structure determination, and/or use of the BAG beamtime should contact Petri Kursula. 

As part of Nor-Openscreen and EU-Openscreen, we offer high throughput and fragment screening.

High throughput screening (HTS)

The HTS assay we use is a thermal shift assay called differential scanning fluorimetry (DSF) or Thermofluor. The protein of interest is heated up in the presence of a fluorescent probe (Sypro Orange or similar) which reports exposed hydrophobic areas. Thus, you get increased fluorescence when the protein unfolds, which can be used to determine the melting point. If a compound binds to the native state of a protein, there will be a shift in the melting point.

The samples are prepared in 384-well RT-PCR plates, and standard RT-PCR instrument from Roche is used to record the unfolding curves of 384 samples simultaneously.

Fragment screening

For fragment screening, we have a divers 700 compound library, and a library containing 300 small acids. The libraries can either be screened using an Octet red 96 or a Biacore T 200 instrument.

In addition to our own libraries, we also host the 100k European Chemical Biology Library (ECBL) and the 1000-member fragment library.

To discuss your screening needs, contact Aurora Martinez for HTS and Ruth Brenk for fragment screening.

As part of Nor-Openscreen and EU-Openscreen, we offer the following computational chemistry services:

HTS analysis - get more value from your screen

• Based on the hit list and the compound structures in the screening set, we can analyze your screen to give you information about structure-activity relationships (SAR). This can help you to assess the value of the hit compounds and to guide their further evaluation.

Hit expansion - explore SAR

• We can screen for analogues of your hit compounds in databases with commercially available compounds. This will help you to quickly explore SAR and to improve the affinities of your hits.

Virtual screening - find new ligands

• In virtual screening, computer stored compound databases or screened for compounds that are either similar to a query compound or that fit into the binding site of a given target. The goal is the generate a list of compounds which are enriched in ligands.

Bespoke services

• We also offer other bespoke services, e.g. druggability assessment, homology modeling, and compound design for hit optimization.

For all of the services, we have access to an in-house curated library of about 7 million commercially available compounds, to other publicly accessible compound database, in house developed software as well as commercial software packages.

For further information and to discuss your needs, contact Ruth Brenk.

General rules: 
The person booking has to be present during operation of the instrument.
Notify biss@uib.no if you exceed the time booked. Booking is mandatory.

If you need training (first-time users), please contact the responsible person for the instrument. 
Juha: Juha.Vahokoski@uib.no
Anne: Anne.Baumann@uib.no
Ju: Ju.Xu@uib.no

Current instrumnet price list

The instruments and services of BiSS are available to both internal and external academic and industrial users.

If you have used BiSS services and/or instrumentation for a publication, you must acknowledge the use of BiSS in your publication as follows:

"We acknowledge the use of the Core Facility for Biophysics, Structural Biology, and Screening (BiSS) at the University of Bergen, which has received infrastructure funding from the Research Council of Norway (RCN) through NORCRYST (grant number 245828) and NOR–OPENSCREEN (grant number 245922)."

In addition, for synchrotron data collected under the various BAGs, the corresponding infrastructure must be acknowledged.

You should inform us of any resulting publications, as we need to report publication data to the funding agency.

Furthermore, users in Norway must link their publications in Cristin to the respective infrastructure grants mentioned above.

The form below is for service projects requiring BiSS staff involvement. Proposals will be evaluated and prioritized by BiSS leadership and staff based on quality, urgency, impact, and available resources. Regular instrument booking and user training should be done via BookitLab.

Proposal form for BiSS service projects

We will assist you in setting up the SEC-MALS.
Simply bring your buffer, samples, and provide the necessary sample information.

Price: 1-2 hours supervised fee (depending on the sample amount, buffer, and whether data analysis is required) + instrument time

If you have further questions, please contact biss@uib.no