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Mass spectrometry (MS), nuclear magnetic resonance (NMR), and electron microscopy (EM) are combined for the characterization of molecular structures. MS group is focused on infection metallomics. Next-generation analytical procedures for non-invasive diagnostics of clinically relevant diseases are developed in close collaboration with Czech hospitals. Obesity, diabetes and neurodegeneration crosstalk are studied by NMR metabolomics. EM equipment has been used in multimodal imaging projects.
We are proposing a basic research project toward a universal noninvasive platform for developing future diagnostics for invasive infections by global pathogens. During infection in critically ill patients, in response to a hostile host environment, secondary bacterial, mycobacterial and fungal metabolism is activated to produce metallophores and microbial toxins, or other virulence factors, that increase the chance of the pathogen's survival. First, we are going to reveal the structures, stability, and threshold concentrations of new specific biomarkers of infection in humans in a cross-sectional study. Second, we are going to achieve a longstanding goal of medical diagnostics by developing a new tool discriminating invasive disease from benign colonization using a clear borderline between proliferation and the steady state. Our work aims for a substantial reduction in the mortality rate in critically ill patients including those with COVID-19-associated coinfections through earlier and more sensitive detection of bacterial, and fungal pathogens that would be overlooked in AspICU (Aspergillus) algorithm.
Supported by Czech Science Foundation, grant No. 21-17044S (2021-2023)
The main aims of the project Prague Infrastructure for Structural Biology and Metabolomics II are the following:
Supported by Academy of Sciences of the Czech Republic, 2020-2022
Cooperation with Medical Faculty, Palacký University in Olomouc, Dr. Milos Petrik
Mixed infections represent an analytical challenge for any microbiology laboratory. In this project high mass resolution spectrometry will be used in newly developed rat experimental models as a molecular tool sensitive enough to describe and monitor mutual microbial combat in a rat model. An early disease detection and whenever possible, non-invasive analytical tools will be developed based on microbial siderophores, specific disease biomarkers, to be detected in urine of infected animals. Special attention will be paid to mixed infections in rat lungs caused by Aspergillus and Pseudomonas, common pathogens participating in cystic fibrosis or patients with chronic obstructive pulmonary disease. The biofilm formation and its decay will be monitored by light and electron microscopy. Multimodal imaging approach, supported by software development, will rely on in vivo data obtained by positron emission tomography/computed tomography. The efficiency of antibacterial/antifungal treatment will be monitored by silencing of siderophore production.
Supported by Czech Science Foundation, grant No. 19-10907S (2019-2021)
The aim of the project is prototype of the system for preparation of advanced therapy medicinal products (expanded cells), enabling the production of gene-modified cells. These cells must be processed in an isolated system (environmental protection against GMO Classes 1 and 2) and expanded in incubators. Because it is an individual preparation of biological material, the preparation of the medicinal product for each patient must be performed individually, avoiding cross-contamination. It will be an innovative isolator workstation according to applicable standards such as cGMP, ISO 14644-7 or ISO 10648-2 with a validateable decontamination process (aimed inter alia at validateable decontamination of RNA, DNA and viruses).
Supported by Technology Agency of the Czech Republic (2021-2023)
(Marek Kuzma in collaboration with David Funda)
Gut microbiota may play a key role in many metabolic diseases, including type 2 diabetes (T2D). Consumption of a high-fat/high-sugar western diet alters human resident microbiota towards reduced genetic diversity and influences its metabolic activity towards enhanced energy extraction. Plant-based diets are useful in treating T2D, but it is not clear whether their effect results solely from diet composition or whether it is mediated, at least partly, by different microbiota and its metabolic activity. One possible therapeutic approach is the replacement of “pro-diabetic” microbiota with its “healthy” variant. Still, we do not know the “healthy” microbiota and under which conditions this microbiota could stay stable and functional. The proposed study aims to identify possible metagenome/metabolome characteristics in different human cohorts (T2D vs vegans) to assess vegan microbiota's stability in a T2D-like environment and to evaluate the possibility to influence human T2D microbiota/metabolome towards more protective composition by dietary intervention.
Supported by the Czech Health Research Council, grant NV18-01-00040 (2019-2021)
Cooperation with Institute of Organic Chemistry and Biochemistry of the CAS (Dr. Lenka Maletínská) and Institute of Physiology of the CAS (Dr. Jaroslav Kuneš)
Obesity, diabetes, cardiovascular and neurodegenerative diseases (so-called civilization diseases) - are the world's leading causes of morbidity and mortality and are responsible for 60% of all deaths. It appears that obesity, type 2 diabetes (T2DM) and neurodegeneration have a common etiopathogenesis involving subclinical inflammation and insulin resistance. In the proposed project, we will explore the efficacy of new lipidized analogs of prolactin-releasing peptide as a complex therapy that simultaneously affects obesity, T2DM and neurodegeneration in mouse and rat models. In parallel, in these models peripheral biomarkers or panel of biomarkers of neurodegeneration development and long-term monitoring of its progression and treatment will be identified using of a comprehensive methodological portfolio including metabolomics in urine and plasma and advanced mass spectrometry imaging methods. Results of this project could help to find a common denominator of these major civilization diseases and open new possibilities for their comprehensive treatment.
Supported by Czech Science Foundation, grant No. 20-00546S (2020-2022)
We have provided spectroscopic data for company drug master files and general analytical expertise in nuclear magnetic resonance spectroscopy, mass spectrometry, and electron microscopy during the long term collaboration. The two-decade partnership is reflected in a series of joint publications in peer-reviewed journals.
Supported by Teva: https://www.tevapharm.com/
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