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The main aims of the project Prague Infrastructure for Structural Biology and Metabolomics II are the following:
Supported by Ministry of Education, Youth and Sports of the Czech Republic, grant LO1509, 2015-2020
Cooperation with Palacký University in Olomouc, RCPTM and BIOMEDREG, Prof. Karel Lemr
Unequivocal determination of the components in complex environment including tissue sections is barely possible by using a single imaging technique. In the three-year frame we will combine hyperspectral data obtained from molecular and elemental imaging mass spectrometry, scanning electron microscopy-energy dispersive X-ray and positron emission tomography. The multimodal fusion and its interrogation with histology evaluation will be used in medically important areas. In accord, tissue imprints on newly designed nanostructure-based surfaces will be probed and applied in early diagnostics of infectious diseases. This proposal represents a hypothesis-driven basic research based on original idea that microbe-specific low molecular weight biomarkers can be visualized either as biomolecules or elements in tissue to provide fundamental information on disease development, progression and treatment as well as on distribution of biomarker metabolites.
Supported by Czech Science Foundation, grant No. 16-20229S (2016-2018)
Cooperation with BOKU – University of Natural Resources and Life Sciences, Department of Food Science and Technology, Vienna, Prof. Roland Ludwig
The project is aimed at elucidation of interactions between cellobiose dehydrogenase (CDH) and its putative redox partner – lytic polysaccharide monooxygenase (LPMO) – in solution and in their cellulose bound state. The research strategy is based on the combined expertise of both research partners. The Austrian group will perform protein engineering and production as well as in-solution spectrophotometry and calorimetry to monitor CDH-LPMO electron transfer rates and interactions. The Czech team will employ structural mass spectrometry techniques based on protein isotopic exchange and chemical cross-linking to investigate the structural details of the protein-protein and protein-substrate interactions. The results will answer the questions if CDH functions as an “LPMO reductase” and if specific interactions are involved in their interprotein electron transfer. This will expand our understanding of biocatalytic redox processes of cellulose depolymerization, which may help increasing the efficiency of biofuel production or degradation processes in biorefineries.
Supported by Czech Science Foundation, grant No. 16-34818L (2016-2018)
Cooperation with Charles University in Prague, Department of Parasitology, Prof. Petr Volf
The project focuses on the species identification of Leishmania and their vectors, phlebotomine sand flies, by MALDI-TOF MS protein profiling; we aim to develop rapid, simple, reproducible and cost-effective method. A collection of reference protein spectra will be established, comprising sand fly species of the Mediterranean, Middle East and Caucasus region; protein profiles of larval and pupal stages will also be characterized. The reference set will be based on sand flies reared in a unique collection of laboratory colonies as well as obtained by field collections. The discriminative power of the method will be determined by studying different sand fly populations from geographically distant regions. Three major causative agents of human leishmaniases of the Mediterranean region (Leishmania infantum, L. tropica and L. major) will be identified in experimentally infected sand flies and sand flies collected in endemic foci. For the first time, MALDI-TOF MS method will be used for detection and identification of pathogens directly in the vector.
Supported by Czech Science Foundation, grant No. 15-04329S (2015-2017)
Cooperation with Intitute of chemical technology, Prague
Asymmetric synthetic methods are gaining on popularity owing to their high atom economy. Enantioselective hydrogenation is among the
most widely-used methods.
The aim is to design and synthesize heterogeneous catalysts for asymmetric hydrogenation. Two catalyst families will be examined – the Noyori-Ikariya and Baratta complexes. While the first one (less reactive) can reduce a range of structurally different ketones and imines, the latter is extremely active in ketone hydrogenation (yet bearing oxygen-sensitive phosphine ligands). The two catalyst families will thus complement each other by possessing different benefits.
The heterogeneous catalysts will be based on metal-organic frameworks, which allow ordered distribution of active sites represented by complexes known from homogeneous catalysis (i.e., single-site heterogeneous catalysis concept). This way of heterogenization is unprecedented in the studied field and hence of high scientific importance. In addition, the mechanism of hydrogenation with Baratta catalysts will be studied as so far it has been explained only partially.
Supported by Czech Science Foundation, grant No. XXX (2015-2017)
Cooperation with Institute of Organic Chemistry and Biochemistry and 1st Medicinal Faculty
Both type 2 diabetes (T2DM) and severe lipotrophic diabetes are associated with insulin resistance. Disturbed endocrine function of adipose tissue at obesity or its absence at lipodystrophy contributes to development of insulin resistance. The proposed project will follow metabolic changes in mice with insulin resistance resulting either from obesity induced by high fat diet or from lipoatrophy. Moreover, impact of therapeutic interventions with different antidiabetic drugs (gliptins, metformin) on metabolic profile will be investigated using NMR-based metabonomic approach. An implementation of both standard biochemical methods and metabolic profiling will enable to characterize two different mouse models of diabetes, acquire comprehensive information about altered metabolic pathways connected with insulin resistance, and compare therapy efficiency. Such information could significantly contribute to the rationalization of therapeutic procedure for T2DM, based on metabolic fingerprint of patient before therapy onset.
Supported by Czech Science Foundation, grant No. P301/13-14105S
Cooperation with 1st Medicinal Faculty, Institute of Chemical Technology Prague and General University Hospital in Prague
Obesity, diabetes mellitus type 2 (T2DM) and their complications are one of the most pressing medical problems today. One of the central processes of bonding obesity, T2DM and their complications is considered subclinical inflammation characterized by infiltration of adipose tissue by immunocompetent cells, especially macrophages. In addition to macrophages in the development of subclinical inflammation in adipose tissue is likely to cooperate also other immunocompetent cells. The project aims to clarify the role of immunocompetent cells in adipose tissue and their interaction with circulating cells in etiopathogenesis of imunocompetent subclinical inflammation, insulin resistance and other associated complications. The cellular composition of adipose tissue in terms of representation of immunocompetent cells and their relationship to their precursors in peripheral blood of patients with obesity and obesity and/or diabetes mellitus conditions and after weight reduction (low calorie diet, weight loss surgery) will be monitored. The project will contribute to improving the understanding of basic etiopathogenic mechanisms leading to the emergence of T2DM and associated complications. It may also help to identify new therapeutic targets, allowing to better meet the current global pandemic of obesity, T2DM and associated diseases.
Supported by Ministry of Health, grant NT/13299 - 4
(Miroslav Kolařík, Vladimír Havlíček)
The capacity to enter hibernation and/or daily torpor is an adaptive physiological trait that enables survival of climatic extremes and food scarcity. Here we plan to investigate variation of organismal and cellular responses to multiple stressors in hibernating bats in relation to torpor-arousal patterns and the associated profound changes of body temperature and metabolism. We will quantify parameters of health and the microbiome of bats, identify pathogenic microorganisms and their factors of virulence and link pathogenic pressure and the cellular response to stressors with genomic variability. Using cutting-edge in vitro tools of tissue-derived bat cells, we will examine
Supported by Czech Science Foundation, grant No. 17-20286S (2017-2019)
The project is focused on the development of a technology for biodegradation of persistent pharmacologically active ingredients (APIs: diclofenac, ibuprofen, ketoprofen and sulfamethoxazole, called “emerging pollutants”) which are continuously introduced in aquatic environment through their high consumption by society. Technology is based on the application of natural bacterial isolates increasing the efficiency of the APIs biodegradation in wastewater in the course its treatment in wastewater treatment plant (WWTP). The goal of the project is to characterize existing bacterial strain capable of degradation of selected APIs, screening and testing of alternative microorganisms, characterization of the degradation processes in water and activated sludge mediated by microorganisms, monitoring of a pollutant during the treatment process and development of analytical procedures for the determination of different forms of the APIs. Newly developed technology will be tested on a pilot scale model of the WWTP. Its implementation will significantly reduce pollution of surface waters and increase the sustainability of water resources.
Supported by the Technology Agency of the Czech Republic, EPSILON Programme, grant TH02030337 (2017-2020)
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