News:

  • 2020/03/26:

    CIISB offers priority and free-of-charge access for COVID-19 research proposals! More here

  • 2020/03/05:

    Cellulose degradation combo by Franta. Two papers arising from collaboration with Roland Ludwig and Daniel Kracher are out. One in Biomolecules and another in Biotechol. Biofuels.

  • 2020/03/05:

    Another TNA access under EU_FT-ICR_MS H2020 Project resulted in joint paper with Erik Sedlak from Kosice. Now published in Scientific Reports.

  • 2020/03/03:

    Dmitry Loginov joined our lab. Welcome Dmitry!

  • 2020/02/28:

    Our systematic effort to understand what is going in chemical cross-linking resulted in another paper. This time about the cross-linker polarity. Enjoy author's copy available for 50 days.

  • 2020/01/23:

    Collaboration with Obsil's team on the interaction between 14-3-3 and caspase-2 was accepted in FEBS J.

Horizon 2020
EPIC-XS
EU FT-ICR MS

Important:

  • 2020/01/07:

    Call for EPIC-XS proposals was closed on Dec 31, 2019. Get ready for next round which closes on March 31, 2020! Submit via the online submission system.

  • 2019/11/12:

    We are looking for post-doc and PhD to join our team and work on various projects using structural mass spectrometry! Inquiries should be addressed to Petr Novak.

  • 2019/03/27:

    We are part of another Horizon 2020 project EPIC-XS (reg. no 823839) focused on the cutting edge proteomic techniques. This project provides Trans-National Access and also focuses on the development of the techniques.

  • 2018/01/03:

    Our lab is a part of Horizon 2020 project EU FT-ICR MS (reg. no 731077). Through this project you can access our expertise as well as other participating FT-ICR labs. Check Trans-National Acess web section for more details. Also, various FT-ICR focused courses and schools are organized by the labs participating in the project.

  • 2017/12/20:

    Bachelor and master theses are available in the lab. Areas of structrual biology, cutting edge mass spectrometry and cell signalling are awaiting new students. Check the tab Teaching.

Research

Focus

Structural mass spectrometry

method development

  • novel covalent labeling and cross-linking chemistry of proteins /nucleic acids
  • new acid proteases as a tool for protein digestion
  • automation of HDX-MS and CX-MS workflow including software design
and application to selected biological problems (medicinally or biotechnologically important proteins), membrane proteins, dynamic and heavily modified proteins and their complexes

Functionalized surfaces for mass spectrometry

  • ambient ion landing protein immobilization
  • surface Immuno-affinity substrates for clinical diagnostics
  • biochemically active plates for desorption mass spectrometry

Current projects

  • European Network of Fourier-Transform Ion-Cyclotron-Resonance Mass Spectrometry Centers

    The European Proteomics Infrastructure Consortium providing access (EPIC-XS) consists of a unified network of experienced access providers and research groups who share a common goal; to facilitate the development and sustainability of proteomics exploration to all life science researchers within the European Union. The initiative is coordinated by Albert Heck, professor of Biomolecular Mass Spectrometry and Proteomics at Utrecht University. EPIC-XS will provide scientists transnational access to high end proteomics technologies and resources. The project will strengthen and expand the European proteomics community through its expertise in proteomics. It’s excellent training courses and programs, available to both novices and experts, will attract new research communities who will be schooled in advanced proteomics technologies. The initiative brings together some of the most world renowned proteomics laboratories and researchers. The community has expertise in accommodating and guiding researchers within the life sciences, as many of the members also participated in the pan- European PRIME-XS initiative, which ended in 2015.

    Funded by EU H2020 (EPIC-XS), project number 82383

  • European Network of Fourier-Transform Ion-Cyclotron-Resonance Mass Spectrometry Centers

    EU_FT-ICR_MS proposal aims to establish a European network of FT-ICR (Fourier Transform Ion Cyclotron Resonance) mass spectrometry (MS) centers in association with a manufacturer and a SME software company. Mass spectrometry (MS) has become the most ubiquitous analytical techniques in use today, providing more information on the composition and the structure of a substance from a smaller amount of sample than any other techniques. Unlike other analytical techniques, such as NMR, which mainly rely on a unique technology, MS is characterized by the existence of a large range of mass analyzers. FT-ICR MS is the most powerful MS technique. It offers up to 100 fold higher mass resolving power and mass accuracy than any other MS technique. On the contrary to NMR community with which the FT-ICR MS shares several features, FT-ICR MS has never been involved in a European INFRA network and so will be a legitimate candidate to the Integrating Activities for Starting Communities call. The EU_FT-ICR_MS network includes 10 FT-ICR MS centers from 8 different European countries (Belgium, Czech Republic, Finland, France, Germany, Italy, Portugal, and United Kingdom) and 1 third country (Russia), a European FT-ICR MS manufacturer and 2 SMEs. It includes centers equipped with up-to-date FT-ICR MS and expertise which will cover most of the field in which FT-ICR mass spectrometry is involved: BioOrganic & BioInorganic, Cultural heritage, Glycomics, Environment, Imaging, InfraRed Spectroscopy of Ions in the Gas Phase, Lipidomics, Medicine, Petroleum & Coal Oil, Nanoparticles, Organic chemistry, Physical chemistry, Proteomics, Structural biology. The EU_FT-ICR_MS proposal contains six work-packages which cover all the aspects of the INFRAIA-02-2017 (RIA) Integrating Activities for Starting Communities (WP1 Transnational access; WP2 Training and Education; WP3 Open Data and e-Infrastructure; WP 4 Joint Research Action; WP 5 Dissemination; WP6 Consortium management).

    Funded by EU H2020 (EU_FT-ICR_MS), project number 731077

  • Mapping the protein surface accessible area utilizing Top Down mass spectrometry and reactive radical footprinting.

    Structural proteomics has become an emerging technique of current structural biology. It covers very broad range of analytical methods from hydrogen/deuterium exchange to chemical crosslinking. Although, the limitations and potentials of both techniques are well studied, foundations of covalent labelling are still poorly described. While H/D exchange offers information about backbone accessibility, covalent labelling targets amino acid side chains and thus provides complementary structural information. In this proposal we will develop chemical reagents with novel reactivity that will allow targeting of more amino acid side chains and expand the spatial resolution of the method. We will also pursue hydroxyradical footprinting where we aim mainly at the development of top-down mass spectrometric approaches allowing to assign not only the site of the modification but also to assess the reactivity scale of individual modified residues. Such advancements will greatly facilitate protein structure characterization and will provide valuable information for protein structure modelling.

    Funded by Czech Science Foundation (19-16084S)

  • Recognition and Validation of Druggable Targets from the Response to Cognitive Behaviour Therapy in Myotonic Dystrophy type 1 patients from Integrated -Omics Networks.

    Myotonic dystrophy type 1 (DM1), the most common adult form of muscular dystrophy, affects virtually all tissues; the noncurable condition carries significant morbidity and mortality impacting patient and family quality of life and socio-economic status. The OPTIMISTIC clinical trial has shown that Cognitive Behaviour Therapy (CBT), a patient-tailored intervention to increase activity and enable patients to deal with their disease, imparts significant beneficial impact on activity and participation. We now propose a multi-omic approach to identify the molecular signatures of the response to this clinical intervention, taking advantage of the thorough clinical characterization of the enrolled patients and the comprehensive set of serum samples at baseline and two follow-up time points. Our central hypothesis is that pathways associated with the positive response to CBT can be consolidated or reinforced by conventional drug therapies targeting the same pathways. A network-based bioinformatics approach shall be used to identify drug targets in the molecular signatures. We shall repurpose clinically approved drugs measuring impact on molecular profiles of patients cells and the behaviour of DM1 mouse models. Repurposed drugs with effects similar to CBT can be evaluated in isolation or combination with other treatments in future clinical trials for DM1 and other neurological conditions. The drug repurposing strategy based on the reverse engineering of a positive response to a behavioural intervention may set the scene for future drug development trajectories for rare diseases.

    Funded by EU - E-Rare (ReCognitiON)

  • Functional Assays for Rapid Microbiological Diagnostics of Selected Health-Care Associated Infections.

    Health-care associated infections (HCAIs) significantly influence current medicine and may limit the progress in many medical procedures. Treatment of such infections has been increasingly complicated by the spread of antimicrobial resistance (AMR). To reduce risks of inappropriate initial therapy, the availability of rapid diagnostic microbiological assays is of utmost importance. Especially, functional diagnostics (i.e., detection of enzyme activity) is important in era of horizontal gene transfer. Functional assays for detection of selected bacterial toxins (ToxB of C. difficile and YopT of Y. enterocolitica) using affinity MALDI will be developed and validated. Simultaneously, functional assay for detection of carbapenemase activity developed in the laboratory of co-investigator will be further optimized and validated. Further, a new assay for functional detection of lipid A modification detecting colistin resistance will be also developed. All of those assays and tests represent a challenge for symptom-based microbiology and functional detection of important antibiotic resistance. Introduction of such assays to routine diagnostics will help to detect potentially unknown pathogens emerged because of horizontal gene transfer.

    Funded by AZV (NV19-05-00541)

    • Past projects

    • Czech Science Foundation (16-24309S) Mass Spectrometric 3D Structure Analysis of DNA Response Elements / Transcription Factor Association and Modeling (2016-2018)
    • Czech Science Foundation (16-20860S) Structural and functional analysis of Hsp70/Hsp90 chaperone complexes (2016-2018)
    • Ministry of Education, Youth, and Sports (COST CZ LH15010) A new tool for structure biology: Combination of high resolution mass spectrometry, chemical cross-linking and H/D exchange (2015-2017)
    • Ministry of Education, Youth, and Sports (Kontakt II LH15010) Structural mass spectrometry analysis for complexes of transcription factors with DNA response elements (2015-2017)
    • Czech Science Foundation and FWF (Austria) (16-34818L / I 2385-N28) Electron Transfer in Cellulose Degrading Enzymes (2016-2018)