Research facilities for GUIDE researchers

In addition to the ample availability of standard techniques and equipment, including C-laboratories (radioactive materials), Biohazard facilities (C1, VMT, D1 and D2 facilities to work with genetically modified organisms and animals), Laser Dissection Microscopy, Confocal Scanning Microscopy, the employees of GUIDE have access to a series of special and advanced facilities provided by the institute itself, the UMCG, the Graduate Schools GUIDE and BCN, as listed below.

Facility / Contact Description
PET Centre

Prof. R. Dierckx, MD/PhD
e-mail Prof. Dierckx

Dr. A.M.J. Paans, PhD
e-mail Dr. Paans

Pet Center

The PET Centre is a joint venture of the AZG and the university. It is an autonomous institute, under direct supervision of the University Hospital's executive board. Research efforts involve a number of disciplines such as cardiology, neurology and oncology. Attention is paid to basic research, patient-related research and clinical care. The PET-centre has a cyclotron for the production of the four most relevant PET radionuclids: 11C, 13N, 15O en 18F, with half life times of respectively 20, 10, 2 and 110 minutes. A radiochemical/ radio-pharmaceutical laboratory is also available. Two positron cameras are available for the measurements and distribution of the radio-pharmaca in vivo (functional imaging). Research focus: analyses of multi drug resistance, visualisation of proteins (receptors and enzymes), visualisation of protein-ligand interactions, and the monitoring of gene therapy using TK transfected tumour models.
Proteomics

Prof. R.J. Vonk, PhD
e-mail Prof. Vonk

Prof. R. Bischoff, PhD
e-mail Prof. Bischoff

Prof. W.J. Quax, PhD
e-mail Prof. Quax

proteomics

 

A Mibiton funded proteomics facility is available employing protein-chip arrays (SELDI-TOF-MS), protein-protein binding (Biacore 3000), and protein detection (multidimensional HPLC-MS).
Genotyping

Dr. G. van der Steege, PhD
e-mail Dr. van der Steege

more information

genotyping megabase

 

genotyping pipeting robot

The FMS/AZG employs a central Genotyping Unit, located at the Medical Biology Division of the Department of Pathology and Laboratory Medicine. This unit serves as a DNA isolation and genotyping facility for all Groningen research groups, both clinical and non-clinical. In addition, being partly funded by Mibiton, the facility also collaborates with commercial partners.

In the unit two 96-channel MegaBACE capillary sequence analyzers, two 4x384-wells and two 2x384-wells PCR machines, and robotics for automated sampling are in operation. A high throughput 384-wells ABI Prism 7900HT apparatus is used for SNP genotyping and quantitative real-time PCR. A general research theme is to locate and identify genetic factors involved in complex diseases with unknown heritable status and components. In most studies the relatively stable and homogeneous population of the Northern part of the Netherlands serves as an excellent source of patient and control DNA. Mapping of disease traits is done by employing micro-satellite markers from regions of interest, or flanking candidate genes, for genotyping of patients and controls, preferably using so-called ‘trios’ (patient with parents, or patient with partner and child) so that also phase information can be included. Various statistical methods are used to study disease association, including haplotype-based methods. Additionally, SNP markers are used to further studying the association of genes with complex disease. High-density SNP databases are available from both the public domain as well as Celera, but sequence searches for new SNP’s are performed as well. Last but not least SNP’s, that are known already to be associated with disease, can be analysed via various protocols.

With the current setting the facility has a capacity of producing about 400,000 genotypes yearly, including microsatellite marker and assay development. The facility also offers support for various statistical analyses and bioinformatical questions.

Central Flow Cytometry Unit

Dr. B.J. Kroesen, PhD
e-mail Dr. Kroesen

Flow cytometry unit UMCG

Flow cytometry unit UMCG

Flowcytometry provides an unequalled technique for the analysis of rare cell types in the context of larger populations of cells. Combined use of defined flowcytometric reagents not only allows to identify minute numbers of specific cells in a total population but also enables to elucidate key aspects of their biological function. Moreover, flowcytometric cell sorting techniques, up to the level of single cell sorting, permit further investigation and modulation of specific cell populations for scientific or clinical purposes under experimentally defined conditions.
Since flowcytometry is a technique employed by many researchers, the Central Flowcytometry Unit (CFU) provides an important facilitating role in many of the research lines of the Faculty of Medical Sciences. The CFU accommodates three flowcytometers: a FACS-Calibur (Becton Dickinson), which is full time dedicated for clinical routine-based diagnosis purposes, a Coulter-Elite (Beckman Coulter), on which all research-based multicolor analyses is performed, and a Moflo (Cytomation), which is full time dedicated for (research) cell sorting purposes. Two flowcytometry operators (Ing. G. Mesander and Ing. H. Moes) are present, who supervise and handle the equipment on a daily basis. Daily coordination is done by Dr. B.J. Kroesen, and the overall supervision is by a “Flowcytometry Administration Committee” comprising the group-leaders of the most regular flowcytometer user-groups.
Bioinformatics
Prof. R.C. Jansen, PhD
e-mail Prof. Jansen

Dr. G.J. te Meerman, PhD
e-mail Dr. ter Steege

Dr. P. Terpstra, PhD
e-mail Dr. Terpstra
The Groningen Bioinformatics Centre (GBIC, head: Prof. Dr. R.C. Jansen) is an initiative of GBB, IWI and GUIDE. It has a bi- location. One part is located at the Biomolecular Sciences and Biotechnology Institute (GBB, Faculty of Mathematics and Natural Sciences) and the other part at the department of Medical Genetics (GUIDE/FMS). The latter forms the GUIDE Bioinformatics satellite. GBIC is a player within the Groningen Genomics Centre (GGC). Access to bioinformatics databases and various educational activities have been implemented during the past years. GBIC seeks the opportunity to participate in the school’s multidisciplinary teams to provide bioinformatics software, hardware, and, importantly, bioinformatics know-how for research.
Clinical Trials Epidemiological Research
TCC:
Dr. H. Hillege, PhD
e-mail Dr. Hillege

CRU:
Prof. G.H. Koëter, PhD
e-mail Prof. Koeter
The Trial Coordination Centre (TCC) is an academic contract research organisation, located within the FMS/AZG, that provides investigators with facilities and resources to enhance biomedical and health research, including project management, data management, methodology, statistics, and report writing. TCC offers services to the pharmaceutical and medical device industry, as well as investigators. The TCC is a professional organisation with a clearly defined structure which focuses on meeting quality standards, budget and time constraints and conforms to the standards of Good Clinical Practice. TCC has extensive experience with large-scale complex data collection activities and management of epidemiological and multi-centre/ national/ international clinical studies. TCC data management activities are built on the software packages ‘Clintrial’ and ‘Oracle Clinical’ which are clinical data management systems used by the pharmaceutical industry and based on the underlying relational Oracle database. The system has been fully validated in accordance with international standards and guidelines. The use of a quality management system ensures that TCC has procedures in place for all working practices. These procedures are subject to regular external audits.
A GCP compliant Clinical Research Unit (CRU) is available for Phase I and II trials. It operates as a joint venture between FMS / AZG and the CRO ‘Pharma Bio-Research’.
Epidemiological Research
Department of Epidemiology:
Dr. H.M. Boezen, PhD
e-mail Dr. Boezen
At the Department of Epidemiology (Dr. H.M. Boezen) extensive knowledge is available for the scientific embedding of large multi-country/multi-centre population based and clinical studies, performed at GUIDE/FMS, a.o. within NNOC and GRIAC. This expresses itself in the advisory function in design, implementation, data management and analyses of these studies with especial expertise in implementation of novel, advanced, and complex longitudinal statistical techniques.
Expression and CGH Arrays
Expression arrays:
Ing. Marcel Bruinenberg, PhD
e-mail Ing Bruinenberg

CGH arrays:
Dr. K. Kok, PhD
e-mail Dr. Kok
Expression and genomic arrays are constructed and applied at the microarray facility of the Department of Medical Genetics (GUIDE/FMS). A BioRobotics MicroGrid II Total Array System allows the production of large arrays of up to 25000 features per slide. For expression profiling micro-arrays are produced containing the Operon Human Oligo Set (V.2, Qiagen), representing 21300 transcripts. For array-based CGH applications, the total collection comprises 8000 large-insert clones evenly spaced throughout the human genome, allowing the identification of genomic losses and gains in tumours and the delineation of microdeletions that underlie congenital anomalies. The facility is furthermore equipped with all the necessary tools for hybridisation and analysis of the micro-arrays. Several specific software packages, including GeneSight and GeneSpring, are available for subsequent data processing.
GMP Facility

Dr. J. van Zanten, PhD
e-mail Dr. van Zanten

 

According to new European legislation the production of (biotechnical) therapeutics used in clinical studies phase I should be performed under Good Manufacturing Practices (GMP). This has a major impact on research groups involved in developing new drugs. In order to enable these groups to test proof of principle of the drugs developed in clinical trials, a GMP facility will be realized as a co-operation between GUMC and the University, with involvement of external partners like Sanquin and industry. This facility will be equipped for flexible and small scale production of recombinant proteins (derived from prokaryotic and from eukaryotic expression systems), production of plasmid DNA, and equipped for cell handlings (for instance with stemcells and transfection of various types of cells with non-viral and viral vectors). This facility is expected to be operative in 2006.
Centres for Mass Spectrometry
Dr. A.P. Bruins, PhD
e-mail Dr. Bruins

Prof. R. Vonk, PhD
e-mail Prof. Vonk
The Centre for Mass Spectrometry has two locations.
The FMNS/Pharmacy located Mass Spectrometry Core Facility contains mass spectrometers for Electro Spray Ionization (ESI), Atmospheric Pressure Chemical Ionization (APCI) Atmospheric Pressure Photo-Ionization (APPI) and Matrix Assisted Laser Desorption Ionization (MALDI). Hyphenated methods available are LC/MS, CE/MS and electrochemistry/MS.
The FMS/AZG located Centre for Mass Spectrometry contains a GC-MS, three Isotope Ratio Mass Spectrometers (IRMS) including a Finnigan Delta X-plus. The latter equipment is used for multi-label tracing, suitable for measuring of in vivo enzyme activities for metabolomics (e.g. metabolic diseases), organ function assessment and development of functional foods.
Transgenic Animals Facility
Dr. M. C. Harmsen, PhD
e-mail Dr. Harmsen
The Transgenic Animals facility is embedded in the Medical Biology Section of the Department of Pathology & Laboratory Medicine. The unit is coordinated by Dr. M.C. Harmsen and further employs H. van der Molen for the performance of all animal experiments. Two additional technicians are involved in the maintenance and genetic modification of murine embryonic stem cells. The facility plays an important role in generating adequate animal models that are suitable for studying the basis of disease as well as for the development of novel therapeutic modalities for diseases that vary from cardiovascular disease, autoimmune diseases, to cancer. The main fields of work are: i) generation of transgenic rodents (mice and rats), ii) generation of knockout mouse models, iii) rederivation of (transgenic) animal strains by embryo transfer, iv) cryopreservation of (transgenic) animal strains and 5) breeding of transgenic animal strains. The unit is equipped with the necessary instruments to generate genetically modified rodents such as a dampened microinjection microscope, equipment to produce microinjection needles and an operating microscope required for implanting microinjected oocytes or blastocysts. In the past, expertise was built up on the generation of transgenic mice using small expression constructs as well as using fragments of bacterial artificial chromosomes (BACs), similarly transgenic rat models have been generated using cosmid inserts. The facility has its own embryonic stem (ES) cell culture facility.
Neuroimaging Center
Prof. G.J. ter Horst, PhD
e-mail Prof. ter Horst

Dr. C. Keysersr, PhD
e-mail Dr. Keysers
The BCN Neuroimaging Center is equipped with a 3T MR scanner, TMS equipment and 72 and 128 channel EEG systems. There are computer facilities especially equipped for the analysis of the generated signals and processing into useful images. The center is financially supported by the university (RuG), four faculties (FMW, FWN, PPSW, FdL) and the Academic Hospital (AZG). The primary but not exclusive task of the BCN Neuroimaging Center is functional brain research, but the facilities can also be used for other types of research, like cardiovascular and animal MRI.
Centre for Electron Microscopy
Dr. J.J.L. van der Want, PhD
e-mail Dr. van der Want
The laboratory for Electron Microscopy is located at the department of Cell Biology and serves as a central facility for the FMS and the AZG. The unique feature of Electron Microscopy in bio-medical research is its potential to describe structural details down to molecular dimensions in the context of complex biological systems. The laboratory is equipped with a field emission scanning microscope (JEOL 6301F) with a cryo attachment (Oxford Instruments) that enables inspection of unfixed specimens. A microscope with a CCD camera is available for transmission electron microscopy. It also has a eucentric goniometer which permits inspection at tilting angles of 600. Digital archiving and documentation is achieved by a SIS-program that runs for both the scanning and the transmission microscopes. In addition, two Philips 201 microscopes with conventional analogue cameras are available for routine inspection. Additional equipment is present for the preparation of the specimen. Images can either be scanned by a "Heidelberg" high resolution scanner or printed on a Fuji printer. The research in the laboratory for Electron Microscopy is directed towards the development of technologies that will contribute to research in structural biology projects and actively interact with life science projects from about 20 different groups. Research activities focus on immuno-cytochemical localization of peptides and receptors, using specimen preparation procedures that maintain the structural integrity of the biological objects. Specimen preparation procedures involve pre- and post-embedding gold labeling of epon, lowicryl or cryotechniques using single and serial section techniques for transmission electron microscopy. These include development and characterization of new immunoprobes, enhancement of immuno-labeling techniques for better penetration of labels in thicker specimens, development of enzyme cytochemical and immunolabeling methods applied directly on frozen sections. Research is being performed to develop further correlative light and electron microscope analysis based on the use of photoconversion of fluorescent probes to electron opaque labels. Work is also focused on the development of methods for generating three-dimensional data on spine-formation and synaptic relations among neurons and the transport of vesicles from the Golgi to the synaptic apposition site. Three dimensional analyses are also performed in a combination of scanning and trans-mission together with the freeze-fracture replica techniques and tilting of semi thin sections.
Central Research Facility for Laboratory Animals
Dr. C.P.A.T. Klein, PhD
e-mail Dr. Klein
The Central Research Facility for Laboratory Animals serves two faculties (Faculty of Mathematics and Natural Sciences, primarily the Department of Pharmacy, and the Faculty of Medical Sciences) by housing various kinds of laboratory animals and by facilitating pertaining research studies. Laboratory animals like mice, rats, guinea pigs and rabbits are housed under strictly controlled and SPF conditions. In addition, larger laboratory animals like cat, sheep, goat, pig are held under conventional conditions. Genetically modified organisms (GGO’s; mouse, rat) are made and/or maintained in collaboration with the transgenic animals’ facility. Facilities are present to treat the animals with genetically modified (micro)organisms or gene therapy-constructs. The facility has operations rooms fully equipped for a.o. transplantation and cardiac studies with large animals, and has also micro-surgery rooms for small animals.
Central Medical Library
A.W. Koelstra
e-mail Mrs. Koelstra
The services of the Central Medical Library - for the benefit of research, education and patient care – are available for staff and students of the Faculty of Medical Sciences (FMW), Faculty of Mathematics and Natural Sciences (FWN)– Department of Pharmacy, and the staff of the Academic Hospital Groningen (AZG). The Central Medical Library offers, via its website, i) access to full text electronic journals, ii) access to extensive catalogues (local and national), iii) access to (bio)medical databases (of the Library itself and external databases), iv) information on new acquisitions, and v) an overview of medical and nursing sources and resources on the internet. The library offers additional services to members of staff including i) helping with (re)searching or doing the searching for staff members (First Aid-post for Searching), ii) literature search (extended), iii) alerting services, iv) citation analysis, v) advice and help in handling and processing references (Reference Manager), vi) help in obtaining the publications (document delivery), and vii) organizing courses.

 

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