A. Deusinglaan 1 9713 AV Groningen
Prof. dr. B.N.G. Giepmans
0031 50 361 61 11
UMIC provides the microscopy infrastructure to support state-of-the art research in medical and biological sciences. It offers training and access to advanced light- and electron microscopes as well image processing to local researchers of the UMCG and other faculties of the university Groningen, as well as to (inter)national external users. A key goal is to improve approaches for correlated microscopy (CLEM).
The facility houses several confocal- and fluorescence microscopes, a transmission electron microscope a scanning transmission electron microscope and a recently updated EM-sample preparation lab. The unique expertise of the facility is based on three of these instruments: (i) Zeiss LSM 780 / LSM 7MP combined confocal microscope including a two-photon /OPO laser; (ii) a Zeiss Supra 55 Scanning Transmission Electron Microscope equipped with an ATLAS large-area imaging application; (iii) a DELMIC Secom light microscope integrated in the Zeiss Supra55.
Catchwords for the type of experiments performed are, Intravital, Two Photon, Time Lapse, FRET, FRAP, Large Area TEM, large Area SEM, Correlative Light- and Electron microscopy (CLEM).
Our research focusses on probe development, the fate of pancreatic beta cells in Type 1 Diabetes, blister diseases of the skin and cell-cell junctions. We also facilitate a broad range of projects, from fundamental research up to diagnosis of human diseases. Training of new users is in a 1:1 manner in several collaborative projects. In addition, courses on cellular imaging are provided at different expertise levels (light, basic, advanced).
- Biomedical & health
- 1. Large area electron microscopy (“Nanotomy”)
- 2. Intravital microscopy
- 3. Correlative light- and electron microscopy (CLEM)
- 4. Numerous sample preparation protocols for EM/CLEM
- 5. Molecular biology for generation of genetically-encoded probes
- 1. Type 1 diabetes
- 2. Skin blister diseases
- 3. Liver regeneration
- 4. Cell-cell junctions
Expertise and Track Record
43500984121 Characterization of ultrastructural changes in buccal mucosa using electron microscopy and deep learning with D.J. Robinson (ErasmusMC). 43500984108 Identification of multiple proteins in large scale EM maps using EDX (‘ColorEM’) with N.N. van der Wel (AMC). 435000008 Integrated microscopy using electron-beam excited luminescence: Biomedical implementation with dr. ir. J.P. Hoogenboom (TU Delft). 435002023 Biomedical implementation of fluorescence super-resolution in SEM With Hoogenboom (TU Delft).
Combining large area electron microscopy with high-end light microscopy. Due to these techniques confocal data can be placed in the high resolution context of EM data. Almost any combination is possible including 3D, timelapse, spectral analysis, two-photon, FRAP and FRET (light microscopy); together with TEM, STEM, backscatter/SE SEM (EM). In addition we perform CLEM using a fluorescence-microscope integrated in an EM (Secom, DELMIC). We have a broad expertise, ranging from examination of biomaterials, viruses, bacteria, yeast up to tissues and living animals.
The UMIC started full operation with it’s opening in 2007. We successfully built a state-of-the art imaging center (www.umic.info) financed by the UMC Groningen and several grants, including those from ZonMW, NWO-ALW , STW and FP6. Detailed information on the research and track record of the group leader can be found at www.cellbiology.nl, including links to reviews and research papers on advanced microscopy.
1. Advanced Light Microscopy-related projects:
Intravital imaging of cellular dynamics during inflammation using LM, EM and CLEM (2014). (http://dmm.biologists.org/content/7/7/857.long).
Balancing labeling with preservation and the use of probes for live-cell imaging (2012). www.nature.com/nmeth/journal/v9/n2/full/nmeth.1855.html
We participate in the STW-funded program “Microscopy Valley”to develop CLEM www.stw-microscopyvalley.nl
2. Microscopy implemented in cell-cell junction research:
Role of the cell surface protein EpCAM and mechanistic cause of failure in patients (2013). http://hmg.oxfordjournals.org/content/22/13/2566.long See also: http://www.sciencedirect.com/science/article/pii/S1368837513006398
3. Large scale microscopy (“nanotomy”) implemented in Type 1 diabetes research:
Analysis of Islets of Langerhans in a Type 1 Diabetes rat using mosaic microscopy and open-source access to data (www.nanotomy.nl) equaling over 25.000 traditional electron micrographs (http://www.nature.com/srep/2013/130508/srep01804/full/srep01804.html). Collaboration with LUMC, Leiden. See also: http://link.springer.com/article/10.1007%2Fs00125-013-3043-5
Currently the new technique of nanotomy is implemented in >10 collaborative projects
1. EM-LM: Key in our correlated microscopy is to integrate light microscopy and EM microscopy datasets. Large-scale EM/ nanotomy has been a major step forward to integrate EM data with other datasets. Optimizing probes for both modalities and implementation of new hardware and in biomedical research is key in the aforementioned “Microscopy Valley” and enabling technology 2013 with J. Hoogenboom (Delft).
2. Genomics-Microscopy: Currently, we also aim to integrate EM data with genetic expression profiles. Our contribution is generating the EM data.
- Reis CR, van der Sloot AM, Natoni A, Szegezdi E, Setroikromo R, Meijer M, Sjollema K, Stricher F, Cool RH, Samali A, Serrano L, Quax WJ. Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants. Cell Death Dis. 2010 Oct 21;1
- de Waard H, Hessels MJ, Boon M, Sjollema KA, Hinrichs WL, Eissens AC, Frijlink HW. CLSM as quantitative method to determine the size of drug crystals in a solid dispersion. Pharm Res. 2011 Oct;28(10):2567-74
- Wilts, B.D., Michielsen, K., Kuipers, J., De Raedt, H., and Stavenga, D.G. Brilliant camouflage: photonic crystals in the diamond weevil, Entimus imperialis. Proc. Biol. Sci. 2012. 279, 2524-2530.
- Ozgen H, Schrimpf W, Hendrix J, et al. The Lateral Membrane Organization and Dynamics of Myelin Proteins PLP and MBP Are Dictated by Distinct Galactolipids and the Extracellular Matrix. PloS one 2014; 9:e101834.
- van Wietmarschen N, Moradian A, Morin GB, Lansdorp PM and Uringa EJ. The mammalian proteins MMS19, MIP18, and ANT2 are involved in cytoplasmic iron-sulfur cluster protein assembly. J Biol Chem 2012; 287:43351-43358.
- Yazdani S, Poosti F, Kramer AB, Mirković K, Kwakernaak AJ, Hovingh M, Slagman MC, Sjollema KA, de Borst MH, Navis G, van Goor H, van den Born J. Proteinuria triggers renal lymphangiogenesis prior to the development of interstitial fibrosis. PLoS One. 2012;7(11):e50209.
- Gradstedt H, Iovino F and Bijlsma JJ. Streptococcus pneumoniae invades endothelial host cells via multiple pathways and is killed in a lysosome dependent manner. PloS one 2013; 8:e65626.
- Oenema TA, Maarsingh H, Smit M, Groothuis GM, Meurs H and Gosens R. Bronchoconstriction induces TGF-β release and airway remodelling in guinea pig lung slices. PloS one 2013; 8:e65580.
- Mia MM, Boersema M and Bank RA. Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1. PloS one 2014; 9:e91559.
- Juuti-Uusitalo K, Klunder LJ, Sjollema KA, Mackovicova K, Ohgaki R, Hoekstra D, Dekker J, van Ijzendoorn SC. Differential effects of TNF (TNFSF2) and IFN-γ on intestinal epithelial cell morphogenesis and barrier function in three-dimensional culture. PLoS One. 2011;6(8)
-Member of NL-BioImaging, EU-BioImaging; Together with UMCU and LUMC we form a flagship for CLEM development and implementation
-Part of STW programme “Microscopy Valley”; Project-leader
- EM: Zeiss Supra 55, Fibics Large Area Scan generator, FEI Cm100, JEOL 6301F, Leica (Cryo-)Ultramicrotomes, Leica sputtercoater, Baltec Critical pointdryer.-- CLEM: Delmic SECOM-- Advanced LM: Leica TCS SP2 AOBS, Leica TCS SP8, Zeiss LSM 780, Zeis LSM 7MP, Solamere/Leica spinning disk, Tissuefaxs.-- Dedicated labs: Tissue culture lab, Molecular Biology lab, EM-sample preparation lab
Yes. Large-scale EM data is stored at a password-protected database. Upon publication of the metadata, we in principle aim to make all data available via www.nanotomy.org