CryoEM

CryoEM is particularly useful for objects that are too large, unstable, or variable to be studied by X-ray crystallography or NMR. It can be used to understand the structure, assembly, and function of various biological macromolecule complexes. The cryoEM data can be used with image processing software to make 3D-models. Training in three-dimensional image reconstruction is given through fortnightly to monthly visits for data processing. Cryo-correlative light and electron microscopy (cryo-CLEM) is a unique national service.

Instruct-ERIC Centre Finland / CryoEM

CryoEM services are part of Instruct-ERIC Centre Finland and can be accessed through Instruct-ERIC (Instruct Centre Finland/CryoEM home page). See funding possibilities for Instruct-ERIC access.

• Basic and advanced cryoEM techniques
• Project planning and assessment
• Sample optimisation and preparation
• Plunge freezing services (BSL2)
• Automated single particle and cryo-tomography digital data collection
• Advice on image reconstruction
• Collaborative projects
• Courses in structural biology, cryo electron microscopy and image reconstruction

CryoEM is applicable for projects in e.g. structural biology, nanotechnology, time-resolved assembly and phase transitions. Depending on the approach used, nanoscale resolution can be achieved.

• Single particle averaging and three dimensional (3D) reconstructions
• Electron tomography and 3D-reconstructions
• Measurements and statistical analyses
• Study of biological macromolecular complexes and other electron-beam sensitive materials in aqueous solutions.
• Particle sizes that range from ~10 to 300 nm in diameter.

Leica vitrification robot EM GP

• Automatic plunge freezer for the bare grid technique that is used for the preparation of vitrified fluid samples or extremely thin samples for cryo-EM.
• Suitable for biological suspensions and industrial emulsions in both, aqueous and inorganic solvents. Typical sample volume per grid 3 µL.
• Can be used to plunge freeze samples not only on EM grids, but also sapphire discs and samples in freeze fracture planchettes.
• Temperature and humidity controlled 4-65 degrees C, ambient to 100% humidity.
• Biosafety laboratory level 2.

Cryosol Vitrojet

• Blot-free automatic plunge freezer for clipped bare grid technique that is used for the preparation of vitrified fluid samples for cryo-EM.
• Suitable for biological suspensions and industrial emulsions in aqueous solvents.
• Integrated plasma cleaner
• Temperature controlled (4 degrees C and ambient).
• Typical sample volume 1 µL for 12 clipped grids.
• Biosafety laboratory level 2.

Linkam-Zeiss correlative fluorescence light microscopy for vitrified specimens.

• For detection of fluorescence in vitrified specimens prior to EM. The region of interest can be rapidly located and then used for intance in electron tomography.

FEI TALOS Artica transmission electron microscope equipped with a Falcon III direct electron detector camera and FEI phase plate.

• FEI TALOS Arctica transmission electron microscope with a direct electron detector and a phase plate
• Improved signal-to-noise ratio, greater sensitivity and automated data collection (24/7) enabling high resolution cryo-EM.
• Only system available in Finland and is one of the few in Europe.
• Advanced techniques available include correlative light and electron microscopy for vitrified specimens (CLEM).
• Data can be transferred to the CSC Ltd for processing of frames, or returned on a USB drive.

• CryoEM services are open to both academic and commercial users.
• Projects will undergo scientific review for their feasibility.

Instructions how to start a new project:

1. Contact Behnam Lak or Kiran Ahmad (grp-cryoemservice at helsinki dot fi), or the Instruct-FI hub coordinator (grp-InstructHilifeHub at helsinki dot fi).
2. Have a kickoff meeting.
3. Once sample delivery has been agreed, fill in the CryoEM project form in iLAB.
4. https://hilife-infra.ilab.agilent.com/service_center/show_external/3753/instruc…
5. Samples are brought to Biocenter 1, EM unit floor and delivered to Behnam Lak at an agreed date and time.
6. Samples are made and images are collected and delivered to the customer.

Instruct-ERIC access

Finland is member of Instruct-ERIC that provides open access to research infrastructure in structural biology. Helsinki cryoEM services is one of the service providers.

Services are available to academic and industry researchers from all countries, but researchers from member countries can apply for funding. The funding can be applied for instrument use, consumables, travel and accommodation. For more information about Instruct-ERIC, please see Instruct-ERIC webpages.

ACKNOWLEDGEMENT

Please notice that by using cryoEM service academic customers commit to acknowledge the unit in their publications or theses.  Please remember to add following sentences in your publication. We highly appreciate it.

"We thank Behnam Lak and Kiran Ahmad (University of Helsinki) for technical assistance in cryoEM. The facilities and expertise of the HiLIFE CryoEM unit at the University of Helsinki, a member of Instruct-ERIC Centre Finland, FINStruct, and Biocenter Finland are gratefully acknowledged."

CryoEM services offers full-service and self-service options for CryoEM work. Full-service option covers both sample preparation and imaging. Self-service customers will submit ready-made grids to our facility and imaging will be taken care of by our staff. Prices for both categories are given below.

All prices are VAT-exclusive. Standard rate of VAT is 24%. This price list is only for academic users. Prices for commercial customers are available on request.

Billing is three times a year.

FULL-SERVICE

Including Sample preparation and data collection as service.

Sample Preparation by Plunge freezing technique

• Preparation of cryoEM sample by Leica plunge freezing technique on copper grids*      95 €

                                  * Includes all consumables for three technical repeat grids using standard quantifoil R1.2/1.3 300 mesh Cu grids. Other grid types such as lacey holey carbon film, quantifoil R1.2/1.3 300 mesh Cu with an ultrathin Carbon layer available on request

• Preparation of cryoEM sample by Leica plunge freezing technique and gold grids**      140 €

                               **Includes all consumables for three technical repeat grids using standard UltrAuFoil R2/2 200 mesh Au grids. Other grid types such as Au-flat 1.2/1.3 300 mesh Au and Quantifoil R2/2 Cu 300 mesh coated with graphene oxide available on request

• Preparation of cryoEM sample by Vitrojet blotfree freezing technique on Cu grids*       130 €

                                  * Includes all consumables for 4 grids using standard quantifoil R1.2/1.3 300 mesh Cu grids. Other grid types such as lacey holey carbon film, quantifoil R1.2/1.3 300 mesh Cu with an ultrathin Carbon layer available on request

• Preparation of cryoEM sample by Vitrojet blotfree freezing technique on Au grids**    185 €

                               **Includes all consumables for 4 grids using standard UltrAuFoil R2/2 200 mesh Au grids. Other grid types such as Au-flat 1.2/1.3 300 mesh Au and Quantifoil R2/2 Cu 300 mesh coated with graphene oxide available on request

Data collection with Talos Arctica

Quick-check: 220 €/sample

• Used for sample optimization. Data set of the sample is typically 20 - 150 images. Such a data set will give you general information about your sample such as purity, size distribution and concentration.
• Price includes: Instrument time (Talos Arctica), operator and consumables. Sample preparation is not included.

Large scale data collection for cryo-sample

• Large enough data set for particle reconstruction.

  • 24h, 1000 €. Data set of the sample is typically 500 - 1000 images.

  • 72h, 2700 €. Data set of the sample is typically 1000 - 3000 images.

*Price includes: Instrument time (Talos Arctica), operator and consumables. Sample preparation is not included.

• Zeiss light microscope with cryogenic stage per hour*                                            20 €

   * Sample preparation and related consumables are not included.

Consumables (subject to availability)

Quantifoil R1.2/1.3 300 mesh Cu grids.                                                                              10 €/each

Lacey holey carbon film (subject to availability)                                                                10 €/each

Quantifoil R1.2/1.3 300 mesh Cu with an ultrathin Carbon layer                                  10 €/each

Quantifoil R2/2 Cu 300 mesh coated with graphene oxide                                            25 €/each

UltrAuFoil R2/2 200 mesh Au grids.                                                                                    15 €/each

Au-flat 1.2/1.3 300 mesh Au                                                                                                 25 €/each

Autogrid container                                                                                                                12 €/each

Autogrid (C-clip ring and c-clip)                                                                                           16 €/each

SELF-SERVICE

For eligible customers only. Customer submit cryo grids, no sample preparation service included.

Sample preparation

• Leica EM GP 10 € / h, minimum booking time is 2h. Price includes blotting paper, ethane and LN2.
• Glow discharge   5 € / use

• Clipping station per 30 min    5€                                                                                                             

Purchase of grids and grid containers is customer’s responsibility. If the grid containersupplied by the customer is not suitable for autogrids, grids will not be saved after data collection.

Storage and book keeping of cryogrids is the customer’s responsibility. Sample sheet needs to be filled in for all samples/grids that are stored in CryoEM facilities or submitted to CryoEM service for imaging.

DATA COLLECTION, Talos Arctica

• Self service Arctica 24h                                                                                                   1000 €
• Self service Arctica 72h                                                                                                   2700 €

Cryo electron tomography

In tomography techique the specimen is tilted in the microscope to produce image series. Each image of the series is from same location and the images provide different orientations of the particles.  

• Instrument time 24hr (1000 €)
• Sample preparation not included

Special notes

1. Sample includes max 3 identical replica grids (identical concentration, grid type, sample preparation conditions etc.)
2. If customer submits autogrids, autogrid fee will not be charged
3. If sample is loaded into the microscope, but it is not imaged, Autogrid fee will be charged.
4. We can provide autogrid containers only if we have extra containers in storage.

Useful links about cryoEM

•  The talks from NRAMM Workshop on Advanced Topics in EM Structure Determination: Challenges and Opportunitiesare available on-line at: http://nramm.nysbc.org/2017-workshop-lectures/. Topics discussed  included specimen preparation, imaging, instrumentation, processing and reconstruction, and methods for validation. 

Recent publications

2023

• Es-Haghi M, Neustroeva O, Chowdhury I, Laitinen P, Väänänen M-A, Korvenlaita N, Malm T, Turunen MP, Turunen TA. Construction of Fusion Protein for Enhanced Small RNA Loading to Extracellular Vesicles. Genes. 2023; 14(2):261. https://doi.org/10.3390/genes14020261

2022

• Lauri IA Pulkkinen*, Sarah V Barrass*, Aušra Domanska, Anna K Överby, Maria Anastasina, Sarah J Butcher. 2022. Molecular Organisation of Tick-Borne Encephalitis Virus. Viruses 14(4):792. https://doi.org/10.3390/v14040792
• Zlatka Plavec, Aušra Domanska, Xiaonan Liu, Pia Laine, Lars Paulin, Markku Varjosalo, Petri Auvinen, Sharon G Wolf, Maria Anastasina, Sarah J Butcher. 2022. SARS-CoV-2 Production, Purification Methods and UV Inactivation for Proteomics and Structural Studies. Viruses. 2022 Sep 8;14(9):1989. doi: 10.3390/v14091989. PMID: 36146795; PMCID: PMC9505060
• Aušra Domanska*, Zlatka Plavec*, Visa Ruokolainen*, Benita Löflund, Varpu Marjomäki, Sarah J Butcher. 2022. Structural Studies Reveal that Endosomal Cations Promote Formation of Infectious Coxsackievirus A9 A-Particles, Facilitating RNA and VP4 Release. J.Virol.  2022 Nov 30:e0136722. doi: 10.1128/jvi.01367-22 
• Muniyandi Selvaraj, Shrikant B. Kokate, Gabriella Reggiano, Konstantin Kogan, Tommi Kotila, Elena Kremneva, Frank DiMaio, Pekka Lappalainen, Juha T. Huiskonen, Structural basis underlying specific biochemical activities of non-muscle tropomyosin isoforms, Cell Reports, 2022, 111900, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2022.111900.
• Kotila T, Wioland H, Selvaraj M, Kogan K, Antenucci L, Jégou A, Huiskonen JT, Romet-Lemonne G, Lappalainen P. Structural basis of rapid actin dynamics in the evolutionarily divergent Leishmania parasite. Nat Commun. 2022 Jun 15;13(1):3442. doi: 10.1038/s41467-022-31068-y. PMID: 35705539; PMCID: PMC9200798.
• Kejzar N, Laanto E, Rissanen I, Abrishami V, Selvaraj M, Moineau S, Ravantti J, Sundberg LR, Huiskonen JT. Cryo-EM structure of ssDNA bacteriophage ΦCjT23 provides insight into early virus evolution. Nat Commun. 2022 Dec 3;13(1):7478. doi: 10.1038/s41467-022-35123-6. PMID: 36463224; PMCID: PMC9719478.
• Liina Hannula, Suvi Kuivanen, Jonathan Lasham, Ravi Kant, Lauri Kareinen, Mariia Bogacheva, Tomas Strandin, Tarja Sironen, Vivek Sharma, Petri Saviranta, Anja Kipar, Olli Vapalahti, Juha T. Huiskonen and Ilona Rissanen. (2022) Nanobody engineering for SARS-CoV-2 neutralization and detection. bioRxiv. https://doi.org/10.1101/2022.09.14.507920

• Kelly JJ, Tranter D, Pardon E, Chi G, Kramer H, Happonen L, Knee KM, Janz JM, Steyaert J, Bulawa C, Paavilainen VO, Huiskonen JT, Yue WW. (2022) Snapshots of actin and tubulin folding inside the TRiC chaperonin. Nat Struct Mol Biol. 2022 Apr 21. doi: 10.1038/s41594-022-00755-1.

2021

• Flatt, J.W.,  Domanska, A., Seppälä, A.L., Butcher, S.J. (2021) Identification of a conserved virion-stabilizing network inside the interprotomer pocket of enteroviruses. Commun Biol 4:250  https://doi.org/10.1038/s42003-021-01779-x

2020

• Barreiro, K., Dwivedi, O. P., Leparc, G., Rolser, M., Delic, D., Forsblom, C., Groop, P. H., Groop, L., Huber, T. B., Puhka, M., & Holthofer, H. (2020). Comparison of urinary extracellular vesicle isolation methods for transcriptomic biomarker research in diabetic kidney disease. Journal of extracellular vesicles, 10(2), e12038. https://doi.org/10.1002/jev2.12038
• Mamata Bhattarai, Fabio Valoppi, Sami-Pekka Hirvonen, Sami Hietala, Petri Kilpeläinen, Vladimir Aseyev, Kirsi S. Mikkonen (2020) Time-dependent self-association of spruce galactoglucomannans depends on pH and mechanical shearing. Food Hydrocolloids Volume 102. https://doi.org/10.1016/j.foodhyd.2019.105607.
• Heikki Saari,Tiia Turunen,Andres Lõhmus,Mikko Turunen,Matti Jalasvuori,Sarah J. Butcher,Seppo Ylä-Herttuala,Tapani Viitala,Vincenzo Cerullo,Pia R. M. Siljander &Marjo Yliperttula. (2020) Extracellular vesicles provide a capsid-free vector for oncolytic adenoviral DNA delivery.Journal of Extracellular Vesicles, 9:1, 1747206, https://doi.org/10.1080/20013078.2020.1747206

2019

• Abdelnabi, R., Geraets, J.A., Ma, Y, Mirabelli, C., Flatt, J.W. , Domanska, A., Delang, L., Jochmans, D., Jayaprakash, V.,  Sinha, B.N.,  Leyssen, P., Butcher, S.J., Neyts , J. (2019) A novel druggable interprotomer pocket in the capsid of rhino- and enteroviruses. PLoS Biology 17: e3000281. https://doi.org/10.1371/journal.pbio.3000281
• Domanska, A. Flatt, J.W., Jukonen, J.J.J., Geraets, J.A., Butcher, S.J.  (2019) 2.8 Å resolution cryo-EM structure of human parechovirus 3 in complex with Fab from a neutralizing antibody. J. Virol   93:e01597-18. doi: 10.1128/JVI.01597-18
• Pooch F, Sliepen M, Knudsen KD, Nyström B, Tenhu H, Winnik FM. (2019) Poly(2-isopropyl-2-oxazoline)-b-poly(lactide) (PiPOx-b-PLA) Nanoparticles in Water: Interblock van der Waals Attraction Opposes Amphiphilic Phase Separation. Macromolecules. 2019 Feb 12;52(3):1317-1326. doi: 10.1021/acs.macromol.8b02558. Epub 2019 Feb 1. PMID: 31496543
• Ruokolainen V., Domanska, A., Pellicia, M., Laajala, M., Butcher, S.J., Marjomäki, M. (2019) Extracellular albumin and endosomal ions prime enterovirus particles for uncoating that can be prevented by fatty acid saturation. J. Virol. 93:e01597-18  doi: 10.1128/JVI.01597-18 https://doi.org/10.1128/JVI.00599-19

• Sah-Teli SK, Hynönen MJ, Schmitz W, Geraets JA, Seitsonen J, Pedersen JS, Butcher SJ, Wierenga RK, Venkatesan R. (2019) Complementary substrate specificity and distinct quaternary assembly of the Escherichia coli aerobic and anaerobic β-oxidation trifunctional enzyme complexes. Biochem J. 2019 Jul 15;476(13):1975-1994. doi: 10.1042/BCJ20190314. PMID: 31235482

2018

• Yang, D., Viitasuo, M., Pooch, F., Tenhu, H., Hietala, S. (2018) Poly(N-acryloylglycinamide) microgels as nanocatalyst platform. Polymer Chemistry. 9:4 517-524 doi: 10.1039/c7py01950e
• Hepojoki J, Hepojoki S, Smura T, Szirovicza L, Dervas E, Prähauser B, Nufer L, Schraner EM, Vapalahti O, Kipar A, Hetzel U. (2018). Characterization of Haartman Institute snake virus-1 (HISV-1) and HISV-like viruses-The representatives of genus hartmanivirus, family Arenaviridae. PLoS Pathog. 14:e1007415.

2017

• Russo G, Witos J, Rantamäki AH, Wiedmer SK. (2017) Cholesterol affects the interaction between an ionic liquid and phospholipid vesicles. A study by differential scanning calorimetry and nanoplasmonic sensing. Biochim Biophys Acta. 2017 Dec;1859(12):2361-2372. doi: 10.1016/j.bbamem.2017.09.011. Epub 2017 Sep 11.

2016

• Leon-Velarde CG, Happonen L, Pajunen M, Leskinen K, Kropinski AM, Mattinen L, Rajtor M, Zur J, Smith D, Chen S, Nawaz A, Johnson RP, Odumeru JA, Griffiths MW, Skurnik M. Yersinia enterocolitica-specific infection by bacteriophages TG1 and ϕR1-RT is dependent on temperature-regulated expression of the phage host receptor OmpF. Appl Environ Microbiol. 2016 Aug 15;82(17):5340-53. doi: 10.1128/AEM.01594-16
• Shakeel S., Westerhuis B.M., Domanska, A., Konig, R.I., Matadeen, R., Koster, A.J., Bakker, A.Q., Beaumont, T., Wolthers, K.C., Butcher, S.J. (2016) Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis. Nature Communications 7:11387. doi: 10.1038/ncomms11387.

2015

• Guryanov, S., Liljeroos, L. Kasaragod, P., Kajander, T., Butcher, S.J. (2015) Crystal structure of the measles virus nucleoprotein core in complex with an N-terminal region of phosphoprotein. J. Virol. 90:2849-57. doi: 10.1128/JVI.02865-15
• Shakeel S., Westerhuis B.M., Ora, A., Koen, G., Bakker, A.Q., Claassen, Y., Wagner, K., Beaumont, T., Wolthers, K.C., Butcher, S.J. (2015) Structural basis of human parechovirus neutralization by human monoclonal antibodies. J. Virol. 89:9571-80

2014

• Magarkar A, Mele N, Abdel-Rahman N, Butcher S, Torkkeli M, Serimaa R, Paananen A, Linder M, Bunker A. (2014) Hydrophobin film structure for HFBI and HFBII and mechanism for accelerated film formation. PLOS Computational Biology 10.1371/journal.pcbi.1003745
• Vahokoski J, Bhargav SP, Desfosses A, Andreadaki M, Kumpula EP, Martinez SM, Ignatev A, Lepper S, Frischknecht F, Sidén-Kiamos I, Sachse C, Kursula I. Structural differences explain diverse functions of Plasmodium actins. PLoS Pathog. 2014 Apr 17;10(4):e1004091.

2013

• Hedegaard, S., Nilsson, C., Laurinmäki, P., Butcher, S.J., Urtti, A., Yaghmur, A. (2013) Nanostructured aqueous dispersions of citrem interacting with lipids and PEGylated lipids. RSC Advances 3:24576–24585.
• Hetzel,U., Sironen,T., Laurinmäki, P., Liljeroos, L., Patjas, A., Henttonen, H., Vaheri, A., Artelt, A., Kipar, A., Butcher, S.J., Vapalahti O., Hepojoki J. (2013) Isolation, identification and characterization of novel Arenaviruses, the etiological agent of Boid Inclusion Body Disease. J. Virol. 87:20 10918-10935
• Hirvonen, S, Karesoja, M., Karjalainen, E., Hietala, S., Laurinmäki, P., Vesanen, E., Butcher, S.J., Tenhu, H. (2013) Colloidal properties and gelation of aqueous dispersions of conductive poly(benzimidazobenzophenanthroline) derivatives. Polymer 54:694-701
• Karjalainen, E., Chenna, N., Laurinmäki, P., Butcher, S.J., Tenhu H. (2013) Diblock copolymers consisting of polymerized ionic liquid and poly(N-isopropylacrylamide). Effects of PNIPAM block length and counter ion on self-assembling and thermal properties.  Polym.Chem. 4:1014-1024
• Nilsson, C., Barrios-Lopez, B., Kallinen, A., Laurinmӓki, P., Butcher, S.J., Raki, M., Bergstrӧm, K., Weng Larsen, S., Østergaard, J., Larsen, C., Urtti, A., Airaksinen, A., Yaghmur, A. (2013) SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications. Biomaterials 34:8491-8503
• Pietilä, M.K., Laurinmäki, P., Russell, D.A., Ko, C., Jacobs-Sera, D., Butcher, S.J., Bamford, D.H., Hendrix, R.W. (2013) Insights into head-tailed viruses infecting extremely halophilic archaea. J. Virol. 87:3248-3260
• Pietilä, M.K., Laurinmäki, P., Russell, D.A., Ko, C., Jacobs-Sera, D., Hendrix, R.W., Bamford, D.H., Butcher, S.J.. (2013) Structure of the archaeal head-tailed virus HSTV-1 completes the HK97-fold story. Proc. Natl. Acad. Sci. (USA) 110:10604-10609

2012

• Dearborn, A.D., Laurinmäki, P., Chandramouli, P., Rodenburg, C.M., Wang, S., Butcher, S.J., Dokland, T. (2012) Structure and size determination of bacteriophage P2 and P4 procapsids: function of size responsiveness mutations. J. Struct. Biol. 178:215-224
• Koho, T., Mäntylä,T., Laurinmäki, P., Huhti, L. Butcher, S., Vesikari,T., Kulomaa, M.S., Hytönen, V.P. (2012) Purification of norovirus-like particles (VLPs) by ion exchange chromatography. J. Vir. Methods. 181:6-11.
• Pietilä, MK, Atanasova, NS, Manole, V, Liljeroos, L., Butcher, SJ, Oksanen, HM, Bamford, DH. (2012) Virion architecture unifies globally distributed pleolipoviruses infecting halophilic archaea. J. Virol, 86:5067-5079
• Sarin, L.P, Hirvonen, J., Laurinmäki, P., Butcher, S.J., Bamford, D.H., Poranen, M.M. (2012) Bacteriophage ϕ6 nucleocapsid surface protein 8 interacts with virus-specific membrane vesicles containing the major envelope protein 9. J. Virol. 86:5376-5379
• M. Sedlák: Homopolymer Self-assembly into Stable Nanoparticles: Concerted Action of Hydrophobic Association and Hydrogen Bonding in Thermoresponsive Poly(alkylacrylic acid)s, J. Phys. Chem. B, 116 (8), 2356–2364, 2012.
• Skurnik, M., Hyytiäinen, H., Happonen, L., Kiljuenn, S., Datta, N., Mattinen, L., Williamson, K., Kristo, P., Szeliga, M., Kalin-Mänttätri, L., Ahola-Iivarinen, E., Kalkkinen, N., Butcher S.J. (2012) Characterization of the genome, proteome and structure of yersiniophage φR1-37. J. Virol. 86:12625-12642

2011

• Alhoranta, A., Lehtinen, J., Urtti, A., Butcher, S.J., Aseyev, V., Tenhu, H. (2011) Cationic amphiphilic star and linear block copolymers: synthesis, self-assembly and in vitro gene transfection. Biomacromolecules 12;3213
• Koho, T., Huhti, L., Blazevic, V., Nurminen, K., Butcher, S.J., Laurinmäki, P., Kalkkinen, N., Rönnholm, G., Vesikari, T., Hytönen, V.P., Kulomaa, M.S. (2011) Production and characterization of virus-like particles and the P domain protein of GII.4 norovirus. J. Vir. Methods doi:10.1016/j.jviromet.2011.05.009
• Kumar, V., Butcher, S.J., Öörni, K., Engelhardt, P., Heikkonen, J., Kaski, K., Ala-Korpela, M., Kovanen, P.T.(2011) Three-dimensional cryoEM reconstruction of native LDL particles to 16å resolution at physiological body temperature PLoS ONE 6(5): e18841. doi:10.1371/journal.pone.0018841.