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Running projects

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.

Details

Next Generation Infection Diagnostics

(Vladimír Havlíček)

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)

A prospective study on invasive pulmonary aspergilosis

(Vladimír Havlíček)

The aims of the project are: 1. In a prospective format, to generate critical diagnostic parameters (sensitivity, specificity, negative and positive predictive values) in a larger cohort of patients with invasive pulmonary aspergilosis. 2. To provide a fair kinetic comparison between standard PCR, routine mycological serology, microscopy, microbiology, imaging data, and our next-generation PTX3/siderophore panel. 3. To develop an affinity-based TafC preconcentration workflow for the enrichment of siderophores in human bodily fluids.

Supported by Czech Health Research Council, grant No. NU23-05-00095 (2023-2026)

New generation system for the preparation of advanced therapy medicinal products

(Marek Kuzma)

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)

Spatial metabolomics in central nervous system infections

(Dominika Luptáková)

Bacterial, fungal, and viral pathogens penetrating the nervous system of patients at risk (including neonates) trigger an immune cascade resulting in inflammation, leading to altered metabolic pathways and neuropathological changes in the brain. Blood and cerebrospinal fluid culture, serology, and PCR analysis are invasive with limited sensitivity and specificity. First, in the rat model, we will define the molecular mechanisms by which the pathogens interact with and penetrate the blood-brain and brain-cerebrospinal fluid barriers and correlate microbial invasion with pathological brain metabolism alterations at the regional and subregional levels. Second, we will quantify and correlate host neurotransmitters, neuropeptides, and brain lipids with pathogen-specific virulence metabolic biomarkers by spatial-metabolomics during CNS infection progression. Third, we will develop a noninvasive diagnostic tool for early detection of CNS infections and superinfections based on the proposed host-pathogen metabolic signature in urine and serum specimens and nasal swabs.

Supported by Czech Science Foundation, grant No. 22-06771S (2022-2024)

Development and evaluation of a web-based diet quality screener for vegans

(Marek Kuzma)

The overall aim of the project VEGANScreener is the prevention and early detection of nutritional deficiencies in the diet of European individuals who have adopted mostly plant-based dietary patterns and particularly in the vegan population. To achieve this goal, we will develop and validate a standardized and brief web- and app-based dietary screening tool to assess and monitor dietary intake among vegans, and we will take first steps towards end-user application. A particular challenge for conducting dietary studies in vegans is the accurate and comprehensive assessment of the consumption of vegan and vegetarian foods, such as plant-based milks, meat alternatives, algae, and calcium-rich mineral water and meat alternatives. These foods are not sufficiently inquired about in FFQs of existing cohort studies, such as the NutriNet Sante, Nurses’ Health Study and UK Biobank. Therefore, extracting vegans from those cohorts would not allow for assessing vegan dietary patterns of today. In order to reach the research aims of the current proposal pertaining to the validation of a novel vegan diet screener, 400 vegans across four European countries (Belgium Czech Republic, Germany, Spain) will be newly recruited. The number of subjects needed for the validation of a diet screener is based on our previous experience. We will, however, make use of existing data already collected among vegans, such as the cohorts available in the Czech Republic and Germany whenever possible, i.e. for developing and pre-testing the diet quality metrics. Further, novel biomarker approaches including metabolomics will be applied to work towards identifying vegan subtypes. Lastly, in a first step towards broader end-user acceptability, digital applications geared toward health care providers (informational and educational website) and the enduser vegans (app to self-assess vegan’s diet quality), will be developed and piloted for acceptability and use.

Supported by Ministry of Education, Youth and Sports of the Czech Republic, grant No. 8F22003 (2022-2025)

Contractual work for Teva Pharmaceutical Industries Ltd.

(Marek Kuzma)

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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