<p><strong>The investigation of the organization, function, and dynamics of genomic DNA in chromatin is a challenging topic that can be addressed by fluorescence microscopy. Conventional DNA labeling methods employ metabolically active non-natural nucleoside analogs with subsequent secondary labeling with antibodies or fluorescent tags. But these methods do not allow for truly real-time monitoring of the nascent DNA in live cells due to the background signal of non-incorporated labeled nucleosides abundantly present in the intracellular space.</strong></p>
<p>The researchers led by <a href="https://www.uochb.cz/en/directory/92/tomas-kraus"><strong>Tomáš Kraus</strong></a> from IOCB Prague and <a href="https://hocek.group.uochb.cz/en"><strong>Michal Hocek</strong></a> from IOCB Prague and Charles University designed and synthesized a novel 2′-deoxycytidine triphosphate (dCTP) nucleotide modified with a thiazole orange fluorophore, which can be incorporated into DNA strand by DNA polymerases in vitro as well as in live cells. Upon incorporation of the modified nucleotide into DNA, the fluorescence of thiazole orange moiety exhibits a shorter lifetime that differs significantly from the intercalated non-incorporated form.</p>
<p>Due to this measurable difference, DNA synthesis in live cells can be monitored in real-time using fluorescence lifetime imaging microscopy. This has allowed the scientists to distinguish and monitor cells which are actively synthesizing DNA from the very first moments after the probe treatment.</p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/UOCHB_Novel_fluorescent_probe_for_real_time_imaging_of_nascent_DNA_in_live_cells_Real_time_imaging_of_in_cellulo_incorporation_of_d_COTP_into_genomic_DNA_a0cb58c5a1.jpg" alt="IOCB Prague: Real-time imaging of in cellulo incorporation of dCOTP into genomic DNA."/></p>
<p>This novel approach, published in Angewandte Chemie International Edition journal, can be exploited in studies of genomic DNA organization, dynamics, and function.</p>


Novel fluorescent probe for real-time imaging of nascent DNA in live cells

<p><strong>Dr. Vojtěch Dočekal and <a href="https://orgchem.natur.cuni.cz/vesely/"><strong>Prof. Jan Veselý</strong></a> from the <a href="https://lcms.labrulez.com/companies/257"><strong>Department of Organic Chemistry</strong></a>, <a href="https://lcms.labrulez.com/companies/16"><strong>Faculty of Science, Charles University</strong></a> described a new highly efficient method for the preparation of planar chiral compounds.</strong></p>
<p>The method based on organocatalytic desymmetrization was published in the prestigious journal <a href="https://www.nature.com/articles/s41467-024-47407-0"><strong>Nature Communications</strong></a>. <strong>Congratulations!</strong></p>
<p>Planar chiral [2.2]paracyclophanes contain two suitably substituted benzene nuclei linked at the <em>para</em> positions by ethylene bridges. Such compounds have a wide range of applications either as ligands or catalysts in synthetic chemistry, but also in materials science or medicine. Despite the wide range of applications, only a limited number of studies have been described for their preparation in enantiomerically pure form.</p>
<p>The methodology developed in the asymmetric synthesis group is based on the highly efficient desymmetrization of prochiral [2.2]paracyclophanes substituted with two formyl groups in suitable positions. In a key transformation, one of the prochiral aldehyde groups is selectively transformed to an ester, leading to the formation of a planar chiral product using asymmetric synthesis methods. Methodologies using catalysis by low molecular weight chiral catalysts derived from natural amino acids, more specifically using so-called <em>N</em>-heterocyclic carbenes, have proven to be highly effective for such asymmetric esterification.</p>
<p>In addition to the optimization of the methodology, a study of the scope of application of the developed transformation, or a study of the synthetic applicability of the chiral products, the publication includes a detailed experimental mechanistic study that reveals interesting differences in the reactivity of the starting diformyl[2.2]paracyclophanes.</p>


An innovative approach to planar chiral substances

<h3><strong>About us</strong></h3>
<p>Our laboratory is equipped with high-end mass spectrometry instruments, which offers services in field of <strong>PROTEOMICS</strong> and <strong>METABOLOMICS</strong>. All our services are available for everybody from the academic and non-academic areas.</p>
<h5><a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6#core-facility-services"><strong>Our Services:</strong></a></h5>
<ul>
<li><strong>Preparation of samples</strong> for analysis (cells, body fluids, tissues, plants etc.)</li>
<li><strong>Targeted</strong> or <strong>untargeted</strong> <strong>proteomics</strong> and <strong>metabolomics</strong> analysis</li>
<li><strong>Data analysis</strong> and basic statistical evaluation</li>
<li><strong>Consultation</strong> of experimental design and the results</li>
</ul>
<h5><strong>Proteomics:</strong></h5>
<p>We are modern well equipped laboratory with the technical background able to perform most of the currently used <a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6/untargeted-proteomics.24?t=s"><strong>untargeted</strong></a> and <a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6/targeted-proteomics.25?t=s"><strong>targeted</strong></a> proteomic measurements. We provide full proteomics service, including protein isolation from the supplied sample to evaluation and consultation of the measured data. Since 2015, we handle approximately 300 orders per year (roughly 3000 samples). Results based on measurements from our laboratory were used in dozens of publications. To consult your plan, please contact Karel Harant (karel.harant@natur.cuni.cz) or Pavla Talacko (pavel.talacko@natur.cuni.cz).</p>
<h5><strong>Metabolomics:</strong></h5>
<p>As a service, we provide <a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6/targeted-metabolomics.26?t=s"><strong>targeted</strong></a> and <a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6/untargeted-metabolomics.30?t=s"><strong>untargeted</strong></a> analysis of small molecules. Thanks to the combination of equipment for <strong>LC-MS</strong> and <strong>GCxGC-MS</strong>, it is possible to measure a wide range of small molecules. We use several types of <strong>C18</strong> and <strong>HILIC</strong> stationary phase columns on LC. For GC, we have various columns for different types of analytes. Individual measuremnts must always be consulted in advance, an individual approach and method must be chosen for each group of molecules. Please contact Olga Součková (souckoo@natur.cuni.cz) for LC-MS or Petr Žáček (zacek@natur.cuni.cz) for GCxGC-MS.</p>
<blockquote>
<p><strong>All our services are available for everybody from the academic and non-academic areas.</strong></p>
</blockquote>
<blockquote>
<p><strong>Contact us before you start your first experiment: +420 325 873 925!</strong></p>
</blockquote>
<blockquote>
<p><strong>23.7.2024 Waiting time from “sample to result” is approximately 6-8 weeks.</strong></p>
</blockquote>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_cover_image_7cb6de4462.jpg" alt="BIOCEV: BIOCEV OMICS Mass Spectrometry Core Facility"/></p>
<h3><strong>Services</strong></h3>
<ul>
<li>Preparation of samples for analysis</li>
<li>Untargeted and targeted proteomics</li>
<li>Untargeted and targeted metabolomics</li>
<li>Data analysis and basic statistical processing</li>
<li>Consultation of experiment design and measured data</li>
</ul>
<h4><strong>Untargeted proteomics</strong></h4>
<h5><strong>Up to 8000 identified proteins in one injection.</strong></h5>
<p>A basic type of proteomic experiment. Complete lysate is digested with trypsin. The resulting peptides are desalted and separated on a reverse phase column. Due to the low amount of proteins and the high complexity of the sample, liquid chromatography is currently most often used in nanoflow - hundreds of nanoliters per minute. Liquid chromatography is directly connected to the electrospray of the Orbitrap Fusion or Orbitrap Ascend mass spectrometer. The mass spectrometer measures alternately in two modes: MS¹, where peptide masses are measured in the Orbitrap with high resolution and accuracy, and MS², in which peptides selected from the previous MS¹ scan are fragmented. These are measured either again in the Orbitrap or in the ion trap. The ion trap provides lower accuracy and resolution than the Orbitrap, but is faster and more sensitive.</p>
<blockquote>
<p><strong>We offer untargeted proteomics measurement and analysis of post-translational modifications in different types of samples (cells, tissues, body fluids, plant samples, etc.).</strong></p>
</blockquote>
<blockquote>
<p><strong>Our newest service is &quot;Thermal proteome profiling (TPP)&quot; that allows you direct detection of drug-protein interactions in living cells.</strong></p>
</blockquote>
<h5><strong>Examples of analyses:</strong></h5>
<ul>
<li>LFQ (label free quantification)</li>
<li>TMT (tandem mass tags)</li>
<li>TPP (Thermal proteome profiling)</li>
<li>phosphoproteome profiling</li>
<li>pull-down experiments</li>
</ul>
<h5><strong>Tips for sample handling:</strong></h5>
<ul>
<li>do not use trypsin for cell harvesting</li>
<li>inform us about presence of detergent</li>
<li>always keep in mind same protein loading for pull-down experiments (eg. Co-immunoprecipitation)</li>
<li>do not use phosphatase inhibitors for phosphoproteomic experiments</li>
</ul>
<h4><strong>Targeted proteomics</strong></h4>
<h5><strong>Accurate quantification of selected proteins.</strong></h5>
<p>Method aims to validate the results from an untargeted approach. It is performed on a triple quadrupole in SRM mode or using the MRM method on an Orbitrap. It is an an alternative approach to common techniques such as western blot. The advantage of this approach is the possibility to analyze several proteins (dozens) at once during one injection. This eliminates the problem of finding suitable antibodies.</p>
<blockquote>
<p><strong>The targeted proteomics service is always project specific and we offer it after prior meeting with the customer.</strong></p>
</blockquote>
<p>Parallel analysis of peptides labeled with heavy amino acids is essential. These serve as an internal standards.</p>
<p>The amount of proteins that can be targeted in one injection using a triple quadrupole, is strongly dependent on the concentration of the target proteins in the sample. The lower the expression of the target proteins, the less it is possible to analyze them in one injection due to the need for higher loading times. Information of fragmentation properties of targeted peptides is also important. This is usually obtained from an untargeted experiment, which should precede the targeted proteomic analysis. If the protein of interest was not detected during an untargeted experiment, then its targeted analysis is very difficult. However, in some cases fragmentation information can be obtained from publicly available databases.</p>
<h5><strong>Tips for sample handling:</strong></h5>
<ul>
<li>do not use trypsin for cell harvesting</li>
<li>inform us about presence of detergent</li>
<li>always keep in mind same protein loading for pull-down experiments (eg. Co-immunoprecipitation)</li>
<li>do not use phosphatase inhibitors for phosphoproteomic experiments</li>
</ul>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Targeted_proteomics_1_f0605d8efc.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Targeted proteomics."/></p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Targeted_proteomics_2_f1af260d27.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Targeted proteomics."/></p>
<h4><strong>Untargeted metabolomics</strong></h4>
<p>The goal of untargeted metabolomics is to cover the widest possible spectrum of metabolites present in the sample, their identification, and quantification. The development of this approach was made possible by the recent advances in instrumentation and computing. Our laboratory equipment enables non-targeted analyses by liquid and gas chromatography.</p>
<blockquote>
<p><strong>We offer untargeted analyses of metabolites in various biological matrices and basic statistical evaluation of the data (Figure 2, 3, 4).</strong></p>
</blockquote>
<blockquote>
<p><strong>Our newest service is stable isotope tracing (Figure 1).</strong></p>
</blockquote>
<p>HPLC-MS/MS (Figure 2): Analyzes are performed on Thermo Scientific equipment on an Ultimate 3000 liquid chromatograph coupled to an Orbitrap Fusion mass detector. The measured data are evaluated by the Compound Discoverer software.</p>
<p>GCxGC-MS (Figure 3): Analyzes are performed on a two-dimensional comprehensive chromatograph connected to a Pegasus 4D mass detector. We evaluate the data in ChromaTOF v4.5 software.</p>
<p>The liquid chromatography method covers non-volatile substances, generally polar, soluble in water, and polar organic solvents (methanol, acetonitrile...). The gas chromatography method is more suitable for analyzing stable volatile non-polar substances up to a weight of approx. 1000 Da. The range of measured substances can be increased for both methods eg., by chemical modifications (derivatization) of the analyzed molecules, which adjust their polarity and volatility (for GC) and/or stability (for LC). We choose a suitable technique or a combination of several techniques based on prior consultation with the customer.</p>
<p>The untargeted analysis results in a list of substances found in the samples, a proposal of probable structures, and an indication of the quantity of individual compounds. We also provide a basic statistical evaluation focusing on looking for differences between the tested sample groups (Figure 4).</p>
<h5><strong>Tips for sample handling:</strong></h5>
<ul>
<li>do not use phosphate buffers in the sample</li>
<li>inform us about sample type, growth medium, chemicals used, etc.</li>
</ul>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Untargeted_metabolomics_Fig_1_11750e6992.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Untargeted metabolomics Fig. 1."/></p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Untargeted_metabolomics_Fig_2_5ca1521705.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Untargeted metabolomics Fig. 2."/></p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Untargeted_metabolomics_Fig_3_f4f1050fc5.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Untargeted metabolomics Fig. 3."/></p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Untargeted_metabolomics_Fig_4_b3e198dbc9.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Untargeted metabolomics Fig. 4."/></p>
<h4><strong>Targeted metabolomics</strong></h4>
<p>Targeted metabolomics includes analyses of selected metabolites, which are then detected selectively and with greater sensitivity than applying an untargeted approach. It is also possible to quantify substances both relatively and absolutely. In the case of absolute quantification, it is necessary to supply a suitable labeled analog of the determined substance.</p>
<blockquote>
<p><strong>We offer analysis of primary cellular metabolites - see List of substances.</strong></p>
</blockquote>
<blockquote>
<p><strong>We analyze metabolites in tissues, cell pellets, incubation media, and body fluids (plasma, urine...).</strong></p>
</blockquote>
<blockquote>
<p><strong>We also offer the possibility of developing a method for the analysis of substances that are not in the attached list or for other matrices.</strong></p>
</blockquote>
<p>The attached list contains substances with the analysis of which we have experience. We adapt each method to the type of experiment and matrix. We can develop a method for any substance or group of substances capable of being detected by liquid and gas chromatography techniques (both connected to a mass detector or a UV detector in liquid chromatography). In the case of the development of a new method, it is necessary to supply the standards of these substances.</p>
<h5><strong>Tips for sample handling:</strong></h5>
<ul>
<li>do not use phosphate buffers in the sample</li>
<li>inform us about sample type, growth medium, chemicals used, etc.</li>
</ul>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/BIOCEV_Introducing_BIOCEV_OMICS_Mass_Spectrometry_Core_Facility_Targeted_metabolomics_List_of_substances_a6a4198b34.jpg" alt="BIOCEV: Introducing BIOCEV OMICS Mass Spectrometry Core Facility - Targeted metabolomics: List of substances."/></p>
<h3><a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6#core-facility-equipment"><strong>Equipment</strong></a></h3>
<h4><strong>Mass spectrometers</strong></h4>
<h5><strong>Orbitrap Ascend</strong></h5>
<ul>
<li><a href="https://lcms.labrulez.com/library?instrumentationItems=31-32-33-30&amp;mainauthorItems=3&amp;search=Ascend"><strong>Application in the LabRulezLCMS library</strong></a></li>
</ul>
<p>Thermo Scientific Orbitrap Ascend Tribrid mass spectrometer, offering new capabilities for multiplexed proteomics and native protein characterization. The mass spectrometer enables improved sample throughput, versatility and ease-of-use — producing high quality data with simplicity. More samples can be analyzed at lower concentrations, enabling faster, more sensitive analysis, and macromolecule experiments, that were not possible before, can now be achieved. The new Auto-Ready ion source for calibration maximizes convenience, allowing the user to spend more time on the results, and less time on instrument set-up.</p>
<h5><strong>Orbitrap Fusion</strong></h5>
<ul>
<li><a href="https://lcms.labrulez.com/library?instrumentationItems=31-32-33-30&amp;mainauthorItems=3&amp;search=Fusion"><strong>Application in the LabRulezLCMS library</strong></a></li>
</ul>
<p>Mass spectrometer combining Quadrupole, Ion trap and Orbitrap. The quadrupole is used as a mass filter for the selection of precursors, after which the instrument branches and the ions can travel either to the Orbitrap - a very accurate and high-resolution mass analyzer that uses the Fourier transform to determine their mass, or to the collision cell, where they can be fragmented. From there, the path leads either back to the Orbitrap or further to the linear ion trap. This serves as the second mass analyzer in the device. It is less accurate and low-resolution, but provides greater sensitivity and the possibility of ion fragmentation. Fragmentation products can be isolated in the trap and fragmented again. This enables analysis in MS³ and even higher levels of fragmentation.</p>
<h5><strong>TSQ Quantiva Triple Quadrupole Mass Spectrometer</strong></h5>
<ul>
<li><a href="https://lcms.labrulez.com/library?instrumentationItems=31-32-35&amp;mainauthorItems=3&amp;search=Quantiva"><strong>Application in the LabRulezLCMS library</strong></a></li>
</ul>
<h5><strong>Leco - Pegasus® 4D GCxGC-TOFMS</strong></h5>
<ul>
<li><a href="https://gcms.labrulez.com/library?instrumentationItems=3-13-2&amp;mainauthorItems=24&amp;search=4D"><strong>Application in the LabRulezGCMS library</strong></a></li>
</ul>
<h4><strong>Liquid chromatography</strong></h4>
<ul>
<li>nano LC Thermo Dionex Ultimate 3000</li>
<li>LC Thermo Dionex Ultimate 3000</li>
</ul>
<h4><strong>Sample preparation</strong></h4>
<ul>
<li>KingFisher Flex</li>
<li>vacuum concentrator</li>
<li>Low flow fraction collector - Spider</li>
<li>Bioruptor pico - sonication bath</li>
</ul>
<h4><strong>Software</strong></h4>
<ul>
<li>Spectronaut 19</li>
<li>FreeStyle</li>
<li>ChromaTOF 4.5</li>
<li>Proteome Discoverer 2.2</li>
<li>Scaffold Q+S 4.6.1</li>
<li>Compound Discoverer 3.3</li>
<li>TraceFinder</li>
</ul>
<h5><strong>Software - Freeware</strong></h5>
<ul>
<li>LipidHunter</li>
<li>MaxQuant</li>
<li>Perseus</li>
<li>Skyline</li>
</ul>
<h3><a href="https://www.biocev.eu/en/services/omics-mass-spectrometry-core-facility.6#core-facility-team"><strong>Team</strong></a></h3>
<h5><strong>Mgr. Karel Harant</strong></h5>
<ul>
<li>Head of Proteomic Core Facilty</li>
</ul>
<h5><strong>Mgr. Pavel Talacko</strong></h5>
<ul>
<li>Non-targeted proteomics, targeted proteomics</li>
</ul>
<h5><strong>RNDr. Petr Žáček, Ph.D.</strong></h5>
<ul>
<li>GC / MS specialist, small molecule analysis</li>
</ul>
<h5><strong>Mgr. Veronika Ševců</strong></h5>
<ul>
<li>researcher, preparation of proteomic samples</li>
</ul>
<h5><strong>RNDr. Petr Žáček, Ph.D.</strong></h5>
<h5><strong>Mgr. Veronika Ševců</strong></h5>
<ul>
<li>researcher, preparation of proteomic samples</li>
</ul>
<h5><strong>Ing. Olga Součková, Ph.D.</strong></h5>
<ul>
<li>LC/MS specialist, small molecule analysis</li>
</ul>


Introducing BIOCEV OMICS Mass Spectrometry Core Facility

<p><strong>A research team from <a href="https://icpms.labrulez.com/companies/62"><strong>IOCB Prague</strong></a>, working in collaboration with the University of Tübingen, Germany, and the <a href="https://icpms.labrulez.com/companies/16"><strong>Faculty of Science, Charles University</strong></a>, has developed a new type of contrast agent that can be used in both magnetic resonance imaging (MRI) and positron emission tomography (PET). This breakthrough resolves a major issue that previously hindered the integration of these two imaging techniques into a single device. Their discovery has the potential to significantly enhance diagnosis and subsequent treatment, particularly for kidney diseases and tumors. The research was published in <em>Angewandte Chemie</em>.</strong></p>
<p>For a long time, medicine has been searching for new ways to refine and streamline available imaging methods. The ultimate goal was to combine the benefits of MRI and PET. While MRI is exceptional for imaging internal organs and tissues with high water content, PET can image even very small amounts of matter, making it capable of sensitively detecting molecular markers, for instance, in cancer cells. The fusion of both techniques was challenging because the strong magnetic field in MRI complicates the functioning of the electronics required for PET. However, this issue has been overcome, and hybrid PET/MRI machines are appearing in hospitals as the most advanced imaging technology. The remaining challenge was the development of a dual-purpose contrast agent that would work with PET and MRI simultaneously. The collaborative discovery by Czech and German researchers may be the solution.</p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/UOCHB_Nova_PET_MRI_kontrastni_latka_vyvinuta_v_UOCHB_slibuje_vcasne_odhaleni_skrytych_nemoci_Soucasne_PET_MRI_zobrazeni_zdravych_a_poskozenych_mysich_ledvin_pomoci_dualni_k_7492a0be78.jpg" alt="IOCB Prague: Current PET/MRI imaging of healthy and damaged mouse kidneys using the dual contrast agent [18F][Gd(FL1)]. The imaging provides consistent signals from both PET and MRI. In healthy kidneys, the center of the kidneys appears dark in the MRI image and very bright in the PET image, indicating normal excretion of the contrast agent. The onset of impaired function in one kidney is indicated by the accumulation of the contrast agent and its slow excretion. Precise mapping of MRI and PET data ensures detailed morphological and quantitative analysis of kidney impairment."/></p>
<p>The described approach is simple and effective. <a href="https://lcms.labrulez.com/articles?search=Miloslav+Pol%C3%A1%C5%A1ek"><strong>Dr. Miloslav Polášek</strong></a>, head of the <a href="https://polasek.group.uochb.cz/en"><strong>Coordination Chemistry group</strong></a> at IOCB Prague, where the work started, explains: <em>“Previous attempts to make PET/MRI probes aimed to achieve advanced and specialized functions, which led to complicated molecules with difficult synthesis and a narrow scope of use. We turned this around by designing a molecule that is simple to use and has broad applicability, one that radiologists will intuitively know how to use. It replicates all the favorable properties of current clinical MRI contrast agents and also provides a PET signal. This adds another dimension of information, improving accuracy and opening new diagnostic applications.”</em></p>
<p><em>“Our solution is a cleverly designed molecule that combines gadolinium and radioactive fluorine-18, which is commonly used in medical scans and is easy to obtain. Connecting these two parts required overcoming several problems, including the large difference in the amounts needed for MRI and PET images. We solved this by using an innovative technique to swap nonradioactive fluorine atoms in the MRI contrast agent for radioactive fluorine-18 atoms. The reaction is elegant, fast, and effective. In less than 30 minutes, we can use automated synthesis to prepare enough of this agent to treat five patients,”</em> says Dr. Jan Kretschmer, one of Dr. Polášek’s former PhD students and the first co-author of the study, who currently works at the Werner Siemens Imaging Center at the University of Tübingen in the group of Prof. André Ferreira Martins.</p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/UOCHB_Nova_PET_MRI_kontrastni_latka_vyvinuta_v_UOCHB_slibuje_vcasne_odhaleni_skrytych_nemoci_Dr_Miloslav_Polasek_vedouci_skupiny_Koordinacni_chemie_UOCHB_AV_CR_5b95bcc5bc.jpg" alt="IOCB Prague: Dr. Miloslav Polášek, head of the Coordination Chemistry group at IOCB Prague."/></p>
<p>Prof. Martins describes a potentially groundbreaking discovery made during testing in a mouse model: <em>“Unexpectedly, we found that one seemingly healthy mouse had kidney problems. The right kidney showed systemic filtration patterns that could only be detected with the simultaneous detection of PET and MRI. This approach enabled us to monitor noninvasively, in real time, the biochemical behavior, distribution, and accumulation of the probe in living, healthy subjects, thereby explaining its unexpected behavior. This method represents a pioneering step toward personalized diagnostics, showcasing the significant diagnostic potential of our hybrid molecule. This is a revolutionary discovery in the field of precise imaging. We are on a path that will eventually allow us to determine not only what disease a patient has but also the stage, type, and aggressiveness of the condition.”</em></p>
<p>The new hybrid contrast agent is patented, and researchers are seeking potential investors. According to Dr. Polášek, this compound, originating from IOCB Prague, has properties that make it the first serious candidate for a PET/MRI agent usable in a clinical setting.</p>
<p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/UOCHB_Nova_PET_MRI_kontrastni_latka_vyvinuta_v_UOCHB_slibuje_vcasne_odhaleni_skrytych_nemoci_Dr_Miloslav_Polasek_Dr_Jan_Kretschmer_prvni_spoluautor_studie_Werner_Siemens_0962294d9a.jpg" alt="IOCB Prague / Tomáš Belloň: Dr. Miloslav Polášek, head of the Coordination Chemistry group at IOCB Prague (left), and Dr. Jan Kretschmer, Werner Siemens Imaging Center, University of Tübingen"/></p>


New PET/MRI probe developed by IOCB Prague promises early discovery of covert diseases

An FDA-Validated, Self-Cleaning Liquid Chromatography–Mass Spectrometry System for Determining Small-Molecule Drugs and Metabolites in Organoid/Organ-on-Chip Medium

<p><strong>He is one of only ten scientists working in Europe who secured the prestigious EMBO Installation Grant this year. After four years in the United States, immunologist Matouš Vobořil recently returned to the Faculty of Science at Charles University to build his own team and advance research focused on the development of immune cells and their training in the thymus. His efforts to combat autoimmune diseases have already caught the attention of numerous grant review panels.</strong></p><h5><strong>Reportedly, one of the motivations for your studies was the awareness that in science, there is still more that is unknown than what is known. You made this statement after receiving the Doctorandus Award for Natural Sciences in 2020, adding that during your lifetime you would like to shift something toward the “known” category. How has that been going so far?</strong></h5><p>The topic for which I&nbsp;take the greatest credit to date is one I&nbsp;began exploring during my doctoral studies and fully developed as a&nbsp;postdoctoral fellow in the U.S., and that is inflammation of the thymus. When you delve into the literature and articles focused on autoimmune diseases, eventually you begin to notice that autoimmune diseases often develop after undergoing some kind of infection. This is particularly evident in connection with long COVID. During inflammatory processes in the body, the immune system responds, and we were interested in whether there is a&nbsp;mechanism that recognises this inflammatory response and teaches T-lymphocytes (immune cells) that this is not a&nbsp;problem, but rather a&nbsp;process inherent to the body.</p><p>During my doctoral studies, I&nbsp;investigated the basic inflammatory response in the thymus, without the presence of actual bacterial or viral inflammation. This turned out to be extremely important. Over time, we discovered that the thymus contains many antiviral molecules and molecules that play a&nbsp;key role in allergic reactions or in the recognition of bacteria and viruses. These molecules create a&nbsp;specific environment in the thymus that mimics what may happen in our bodies later in life, and they train T-cells not to respond to these stimuli. I&nbsp;consider this to be my greatest contribution to the field. Of course, there are still many unexplored areas in this field.</p><h5><strong>The interview I was referring to was published in the magazine of the grammar school where you studied, and which proudly acknowledges your scientific achievements. Was that where your interest in science first began to show?</strong></h5><p>The fact that I&nbsp;studied in Dvůr Králové nad Labem was a&nbsp;huge stroke of luck. Not only is there a&nbsp;zoo, where my parents used to work, so I&nbsp;spent a&nbsp;lot of time there, but thanks to that, I&nbsp;also joined the local Natura club, which brought together people interested in nature and was led by the Dobroruk couple. When I&nbsp;was ten, my parents sent me to a&nbsp;nature-oriented summer camp with them, and I&nbsp;ended up staying with them – which is why I&nbsp;also attended the local high school, where Mrs. Dobroruková taught. She was a&nbsp;wonderful teacher. Her classes really encouraged students to think about what’s&nbsp;happening in nature. Thanks to that, I&nbsp;began participating in biology competitions and got involved in the Czech high school research competition. Although my first scientific experiments focused on ornithology, they gave me the opportunity to present scientific data and meet many people from the Faculty of Science at Charles University, including Professor Jan Černý, who lectured our class on immunology. Suddenly, while still in high school, I&nbsp;realized that this was the path I&nbsp;wanted to take.</p><h5><strong>During your master’s studies, you joined the team of immunologist Dominik Filipp at the Institute of Molecular Genetics of the Czech Academy of Sciences, where you then continued as a doctoral student. How did working with him influence you, and where did it lead you?</strong></h5><p>Dominik Filipp had several ongoing projects related to the peripheral immune response, signalling, and identification of viruses and bacteria. The project I worked on focused on a rare population of cells found in lymph nodes or the spleen. I studied the effect of pathogen-recognising receptors on these cells. Since these cells are similar to those in the thymus and I needed a negative control, I used the thymus for that purpose. To our surprise, the result was not negative but positive. This led us to the phenomenon itself and prompted us to begin investigating its consequences in the thymus.</p><h5><strong>You then travelled overseas to study this discovery – which you actually made rather by chance – in detail. What was your experience like at American research institutions?</strong></h5><p>Amazing. I&nbsp;went to the University of Minnesota to work with particular people, especially my future supervisor, Kristin Hogquist. I&nbsp;had met her at several conferences while I&nbsp;was still in my PhD programme, and I&nbsp;had a&nbsp;feeling that our collaboration could work well both professionally and personally.</p><p>But we were also fortunate to pick Minnesota. It’s&nbsp;a&nbsp;great place to live, and at the same time, excellent science is being conducted there. The Center for Immunology, where I&nbsp;worked, rivals the world’s&nbsp;leading scientific institutions in terms of its research results. I&nbsp;think this is mainly down to the highly supportive environment there, which fosters collaboration. Thanks to this, you can really grow as a&nbsp;scientist there.</p><p>In addition, they focus on explaining and describing the chosen phenomenon as a&nbsp;whole, rather than worrying too much about whether it will result in one or five articles, or whether it will take ten years. Their method of funding supports this approach. In a&nbsp;system of short-term grants, as we know it here, you can’t structure research this way. That’s&nbsp;a&nbsp;major disadvantage for us.</p><h5><strong>How did you develop your own research there?</strong></h5><p>It was there that I&nbsp;fully realized the potential of what we had discovered in the lab in Prague. Kristin Hogquist and her team were working on something similar, but it wasn’t until we teamed up that we were able to take it further. I&nbsp;focused primarily on how various antiviral signals or signals triggered during allergic reactions influence T-cell training and defence against autoimmune diseases following viral infections or allergic reactions. Suddenly, it became clear that this was a&nbsp;vast topic and the foundation for establishing a&nbsp;separate subfield of research on tolerance (the training of immune cells in the thymus so that they do not harm the body while remaining capable of fighting pathogens).</p><p>One great thing was that two labs were coming together at the facility: the one led by Kristin Hogquist and the other led by her husband, Stephen Jameson, which focuses on how different types of infections affect T-cell activation and their response. I&nbsp;realised that these two areas needed to be connected, and I&nbsp;based my own research plan on that – namely, to study how the inflammatory environment, actual inflammation, and viral or bacterial infections can retroactively influence processes in the thymus. This is a&nbsp;topic that no one has addressed yet.</p><p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Forum_UK_Voboril_O_imunitnim_systemu_toho_stale_mnoho_nevime_2_b020119f2e.jpg" alt="Forum UK/Petr Jan Juračka: Vobořil: There is still much to learn about the immune system: As head of research, Matouš Vobořil strives to ensure that everyone on his team feels comfortable." srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Forum_UK_Voboril_O_imunitnim_systemu_toho_stale_mnoho_nevime_2_b020119f2e.jpg 234w," sizes="100vw" width="1000" height="667"></p><h5><strong>You mentioned how important it was to you that you got along with Kristin Hogquist not only professionally but also on a&nbsp;personal level. To what extent did you take this “personal” aspect into account when putting together your own team at CU SCI?</strong></h5><p>This is tremendously important to me. Kristin Hogquist is not only an outstanding researcher, but also a&nbsp;very kind person. And that really helped me feel at home in the American environment, which sometimes tends to become highly competitive. I&nbsp;realized that I&nbsp;would like those who will one day work on my own team to feel the same way I&nbsp;did on hers.</p><h5><strong>So far, we’ve been talking about what led you to science. Have you, on the other hand, encountered anything during your career so far that has discouraged you from pursuing science?</strong></h5><p>Moving overseas with my family and my two-and-a-half-year-old son during the pandemic wasn’t the easiest thing to do. We had to apply for a&nbsp;national exemption just so that I&nbsp;and my family would be allowed into the U.S. at all. Fortunately, as an immunologist, I&nbsp;fell into a&nbsp;special category subject to less stringent pandemic restrictions. Packing up the family, moving overseas, and learning to navigate a&nbsp;completely different system is undoubtedly a&nbsp;major challenge. It required sacrifices not only from me, but above all from my wife, who had to put her own career on hold for several years because of mine. This is one of the biggest and most demanding obstacles that scientists and their families must overcome.</p><p>The second major obstacle you have to deal with as a&nbsp;scientist is paperwork – something I’ve only fully realized now that I’m leading a&nbsp;research group. Even though you hear about it from those around you, it still doesn’t prepare you for when it comes. As a&nbsp;trainee, you do science and conduct experiments in the lab, but suddenly everything shifts, and you become a&nbsp;manager and administrator of all sorts of things. I&nbsp;spend about 30 percent of my time on paperwork. It’s&nbsp;not exactly fun.</p><h5><strong>You obtained a&nbsp;Primus grant, a&nbsp;Junior Star grant from the Czech Science Foundation, and most recently an EMBO Installation Grant. What research challenges do you now face with these grants?</strong></h5><p>I&nbsp;would also like to apply for an ERC Starting Grant this year as well. In the Junior Star project, we are studying cell migration to the thymus. We hypothesize that so-called dendritic cells migrate to the thymus from the periphery (skin, lungs, intestines) – that is, from sites exposed to the external environment and inflammation. These cells are thought to bring information about their own antigens to the thymus and teach developing T-cells tolerance. We aim to determine whether this migration actually occurs, under what circumstances, and how important it is for establishing tolerance to specific tissues. This could help answer the question of why autoimmune skin diseases, such as psoriasis, develop following inflammatory processes.</p><p>The second objective is broader. We would like to answer a&nbsp;major question in immunology: <strong>why do autoimmune diseases develop after a&nbsp;person has had an infection? </strong>We want to study how different types of inflammation (viral, bacterial, or yeast infections) affect the training of immune cells in the thymus.</p><p>We would like to introduce a&nbsp;system of so-called “dirty mice.” The entire field of immunological research is based on working with mice raised in sterile conditions so that we can easily manipulate them and observe how these manipulations affect the immune system. In reality, however, the immune system does not function this way. I&nbsp;brought this idea back from the University of Minnesota, where they placed standardized mice in the same cage with mice purchased from various pet stores around Minneapolis. After a&nbsp;few weeks to months, the mice contract almost everything the store-bought mice have, thereby developing a&nbsp;true physiological immune response. Yet they are still the same mice – genetically identical – that we can manipulate. This is an excellent system that allows us to study immune responses in a&nbsp;much more physiological context.</p><p><img src="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/Forum_UK_Voboril_O_imunitnim_systemu_toho_stale_mnoho_nevime_3_c458457e12.jpg" alt="Forum UK/Petr Jan Juračka: Vobořil: There is still much to learn about the immune system " srcset="https://storage.googleapis.com/labrulez-bucket-strapi-h3hsga3/thumbnail_Forum_UK_Voboril_O_imunitnim_systemu_toho_stale_mnoho_nevime_3_c458457e12.jpg 234w," sizes="100vw" width="1000" height="667"></p><h5><strong>Will you be applying for a&nbsp;European Research Council (ERC) grant with that goal in mind?</strong></h5><p>Exactly.</p><h5><strong>In order to succeed in the competition for ERC grants, the projects should push the boundaries of knowledge, which also involves a&nbsp;certain degree of risk. Where do you see the greatest risks in your own research?</strong></h5><p>There are many risks. One of the biggest is that although all the infections we plan to introduce are controlled and well-documented, you still never have full control over them. So it’s&nbsp;possible that not only will the mice become peripherally infected, but the thymus itself will also become infected, which could complicate the experiments. At the same time, this is a&nbsp;physiological system – and I’m talking mainly about the “dirty mice” – which means that each mouse will respond a&nbsp;little differently, and that will generate enormous variability in the samples. Immunologists strive to have the purest system possible, so that when they introduce, for example, a&nbsp;single infectious agent, they can then observe exactly what’s&nbsp;happening there. In this regard, we are actually taking a&nbsp;step back, so to speak, because we want it to be more variable and closer to reality. Setting up and analysing data from such experiments so that they’re reproducible and reveal a&nbsp;real phenomenon can be a&nbsp;real challenge. But that’s&nbsp;the only way we can get closer to real life.</p><h5><strong>The most recent Nobel Prize in Physiology or Medicine was awarded to three immunologists: Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi, who recently gave a&nbsp;lecture in Prague. Did you meet him? How much did awarding the Nobel Prize to immunologists motivate you further in your work?</strong></h5><p>When Shimon Sakaguchi was in Prague, I&nbsp;was still in the U.S., but I&nbsp;did meet him several times at various conferences and even had the opportunity to talk with him on multiple occasions, given that we’re both involved in T-cell research. In our community, people have long been placing bets on when they’ll finally get the Nobel Prize. For me, their discoveries are truly inspiring, but the Nobel Prize itself doesn’t motivate me that much anymore. I&nbsp;find the story behind it to be more interesting. It took a&nbsp;very long time for the scientific community to accept their findings. One of the seminal articles was published in the <i>Journal of Immunology</i>, which isn’t a&nbsp;journal with as high a&nbsp;profile as <i>Nature</i> or <i>Science,</i> and not one where you’d expect to read about such a&nbsp;groundbreaking discovery. It took several years before it became clear just how significant this discovery was. Now I&nbsp;often remind my students of this – even an article in the <i>Journal of Immunology</i> can win you a&nbsp;Nobel Prize, and that is incredibly inspiring.</p><blockquote><h5><strong>Matouš Vobořil, PhD</strong></h5><p>Graduate of the Faculty of Science at Charles University. His research focuses on the development of immune cells in the thymus, the onset of autoimmune diseases, and the function of antigen-presenting cells. After spending four years as a&nbsp;postdoctoral fellow at the University of Minnesota on Kristin Hogquist’s&nbsp;team, he returned to Europe in 2025. Thanks to a&nbsp;Primus grant from Charles University, he established his own research group at the Faculty of Science. He subsequently received a&nbsp;Junior Star grant from the Czech Science Foundation and, this January, an EMBO Installation Grant. For his dissertation, he was awarded the Doctorandus Prize as part of the Česká hlava initiative.</p></blockquote>

Vobořil: There is still much to learn about the immune system 

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