7 results on '"Julia Rechenberger"'
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2. Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae
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Julia Rechenberger, Patroklos Samaras, Anna Jarzab, Juergen Behr, Martin Frejno, Ana Djukovic, Jaime Sanz, Eva M. González-Barberá, Miguel Salavert, Jose Luis López-Hontangas, Karina B. Xavier, Laurent Debrauwer, Jean-Marc Rolain, Miguel Sanz, Marc Garcia-Garcera, Mathias Wilhelm, Carles Ubeda, and Bernhard Kuster
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human gut microbiome ,metaproteome ,data analysis ,mass spectrometry ,proteomics ,clinical proteomics ,multi-omics ,multidrug-resistant Enterobacteriaceae ,Microbiology ,QR1-502 - Abstract
The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.
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- 2019
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3. Selective multi-kinase inhibition sensitizes mesenchymal pancreatic cancer to immune checkpoint blockade by remodeling the tumor microenvironment
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Chiara Falcomatà, Stefanie Bärthel, Sebastian A. Widholz, Christian Schneeweis, Juan José Montero, Albulena Toska, Jonas Mir, Thorsten Kaltenbacher, Jeannine Heetmeyer, Jonathan J. Swietlik, Jing-Yuan Cheng, Bianca Teodorescu, Oliver Reichert, Constantin Schmitt, Kathrin Grabichler, Andrea Coluccio, Fabio Boniolo, Christian Veltkamp, Magdalena Zukowska, Angelica Arenas Vargas, Woo Hyun Paik, Moritz Jesinghaus, Katja Steiger, Roman Maresch, Rupert Öllinger, Tim Ammon, Olga Baranov, Maria S. Robles, Julia Rechenberger, Bernhard Kuster, Felix Meissner, Maximilian Reichert, Michael Flossdorf, Roland Rad, Marc Schmidt-Supprian, Günter Schneider, and Dieter Saur
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Pancreatic Neoplasms ,Cancer Research ,Oncology ,Tumor Microenvironment ,Humans ,Adenocarcinoma ,Immune Checkpoint Inhibitors ,Carcinoma, Pancreatic Ductal - Abstract
KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) is highly immunosuppressive and resistant to targeted and immunotherapies. Among the different PDAC subtypes, basal-like mesenchymal PDAC, which is driven by allelic imbalance, increased gene dosage and subsequent high expression levels of oncogenic KRAS, shows the most aggressive phenotype and strongest therapy resistance. In the present study, we performed a systematic high-throughput combination drug screen and identified a synergistic interaction between the MEK inhibitor trametinib and the multi-kinase inhibitor nintedanib, which targets KRAS-directed oncogenic signaling in mesenchymal PDAC. This combination treatment induces cell-cycle arrest and cell death, and initiates a context-dependent remodeling of the immunosuppressive cancer cell secretome. Using a combination of single-cell RNA-sequencing, CRISPR screens and immunophenotyping, we show that this combination therapy promotes intratumor infiltration of cytotoxic and effector T cells, which sensitizes mesenchymal PDAC to PD-L1 immune checkpoint inhibition. Overall, our results open new avenues to target this aggressive and therapy-refractory mesenchymal PDAC subtype.
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- 2022
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4. Mass spectrometry-based draft of the mouse proteome
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Piero Giansanti, Patroklos Samaras, Yangyang Bian, Chen Meng, Andrea Coluccio, Martin Frejno, Hannah Jakubowsky, Sophie Dobiasch, Rashmi R. Hazarika, Julia Rechenberger, Julia Calzada-Wack, Johannes Krumm, Sebastian Mueller, Chien-Yun Lee, Nicole Wimberger, Ludwig Lautenbacher, Zonera Hassan, Yun-Chien Chang, Chiara Falcomatà, Florian P. Bayer, Stefanie Bärthel, Tobias Schmidt, Roland Rad, Stephanie E. Combs, Matthew The, Frank Johannes, Dieter Saur, Martin Hrabe de Angelis, Mathias Wilhelm, Günter Schneider, and Bernhard Kuster
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Pancreatic Neoplasms ,Mice ,Proteome ,Arabidopsis ,Animals ,Cell Biology ,Molecular Biology ,Biochemistry ,Mass Spectrometry ,Biotechnology ,Carcinoma, Pancreatic Ductal - Abstract
The laboratory mouse ranks among the most important experimental systems for biomedical research and molecular reference maps of such models are essential informational tools. Here, we present a quantitative draft of the mouse proteome and phosphoproteome constructed from 41 healthy tissues and several lines of analyses exemplify which insights can be gleaned from the data. For instance, tissue- and cell-type resolved profiles provide protein evidence for the expression of 17,000 genes, thousands of isoforms and 50,000 phosphorylation sites in vivo. Proteogenomic comparison of mouse, human and Arabidopsis reveal common and distinct mechanisms of gene expression regulation and, despite many similarities, numerous differentially abundant orthologs that likely serve species-specific functions. We leverage the mouse proteome by integrating phenotypic drug (n > 400) and radiation response data with the proteomes of 66 pancreatic ductal adenocarcinoma (PDAC) cell lines to reveal molecular markers for sensitivity and resistance. This unique atlas complements other molecular resources for the mouse and can be explored online via ProteomicsDB and PACiFIC.
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- 2022
5. Greener aromatic antioxidants for aviation and beyond
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Dirk Weuster-Botz, Thomas Brück, Sophie Jürgens, Norbert Mehlmer, Julia Rechenberger, Patrick Le Clercq, Michael Stöhr, Farah Qoura, Dirk Volker Woortman, Martin Untergehrer, Lukas Hintermann, Patrick Oßwald, Franz Bracher, Monika Fuchs, and Georg Eckel
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antioxidant ,Energy Engineering and Power Technology ,Jet fuel ,Combustion ,Chemische Kinetik und Analytik ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Butylated hydroxytoluene ,Organic chemistry ,Scavenging ,Carotenoid ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Kerosene ,biology ,010405 organic chemistry ,Renewable Energy, Sustainability and the Environment ,Chemistry ,fuel design ,Brevibacterium ,biology.organism_classification ,0104 chemical sciences ,Fuel Technology ,Hydrocarbon ,aviation - Abstract
Antioxidants (AO) inhibiting unspecific oxygen reactions are added to most susceptible industrial products, including liquid hydrocarbon-based aviation fuels. Regulatory approved jet fuel, whether synthetic or crude oil-based, requires the addition of performance antioxidants to inhibit radical-induced oxidation during storage and transport. While presently used antioxidants are petroleum-based, there have been no sustainable, less-toxic, bio-based equivalents reported so far. This study addresses the initial evaluation of carotenoid-based antioxidants as a substitution for current alkyl-phenolic antioxidants to kerosene. Inspired from natural products of Brevibacterium and Synechococcus genus synthesized analogues of candidate aromatic carotenoid cleavage products were evaluated for their effects on combustion characteristics of jet fuel, comparative radical scavenging, and endothelial cell-culture cytotoxicity. These bioinspired antioxidants show no adverse effect on jet fuel bulk properties and combustion chemistry. The radical scavenging properties of the evaluated phenolic compounds are superior to non-aromatic β-carotene cleavage products and in range with current alkyl-phenolic additives. Cytological assays demonstrated low toxicity towards human endothelial cells similar to butylated hydroxytoluene (BHT), one of the approved alkyl-phenol based additives to jet fuel, food, and cosmetics. The initial data set suggests, that the evaluated bioinspired compounds do not interfere with normal operations of jet engines and human fuel handling. Further developments towards the sustainable, biotechnological production and application of aromatic carotenoid cleavage products as antioxidants could contribute to reduced non-renewable consumption and possibly being an environmentally more compatible alternative due to their biosynthetic origin.
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- 2020
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6. Prosit: proteome-wide prediction of peptide tandem mass spectra by deep learning
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Johannes Zerweck, Bernard Delanghe, Daniel P Zolg, Tobias Schmidt, Siegfried Gessulat, Bernhard Kuster, Patroklos Samaras, Julia Rechenberger, Karsten Schnatbaum, Tobias Knaute, Hans-Christian Ehrlich, Mathias Wilhelm, Ulf Reimer, Stephan Aiche, and Andreas Huhmer
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Proteome ,Computer science ,Peptide ,Saccharomyces cerevisiae ,Computational biology ,Proteomics ,Biochemistry ,Tandem mass spectrum ,03 medical and health sciences ,Deep Learning ,Peptide Library ,Tandem Mass Spectrometry ,Animals ,Humans ,Database search engine ,Caenorhabditis elegans ,Databases, Protein ,Molecular Biology ,Peptide sequence ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Sequence database ,business.industry ,Deep learning ,Cell Biology ,Peptide Fragments ,Drosophila melanogaster ,HEK293 Cells ,chemistry ,Neural Networks, Computer ,Artificial intelligence ,business ,Software ,Biotechnology - Abstract
In mass-spectrometry-based proteomics, the identification and quantification of peptides and proteins heavily rely on sequence database searching or spectral library matching. The lack of accurate predictive models for fragment ion intensities impairs the realization of the full potential of these approaches. Here, we extended the ProteomeTools synthetic peptide library to 550,000 tryptic peptides and 21 million high-quality tandem mass spectra. We trained a deep neural network, termed Prosit, resulting in chromatographic retention time and fragment ion intensity predictions that exceed the quality of the experimental data. Integrating Prosit into database search pipelines led to more identifications at >10× lower false discovery rates. We show the general applicability of Prosit by predicting spectra for proteases other than trypsin, generating spectral libraries for data-independent acquisition and improving the analysis of metaproteomes. Prosit is integrated into ProteomicsDB, allowing search result re-scoring and custom spectral library generation for any organism on the basis of peptide sequence alone. A deep learning–based tool, Prosit, predicts high-quality peptide tandem mass spectra, improving peptide-identification performance compared with that of traditional proteomics analysis methods.
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- 2019
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7. Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae
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Ana Djukovic, María José Garzón, Cécile Canlet, Vitor Cabral, Rym Lalaoui, Marc García-Garcerá, Julia Rechenberger, Marie Tremblay-Franco, Iván Peñaranda, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Eva María González-Barberá, Miguel Salavert, José Luis López-Hontangas, Miguel Á. Sanz, Jaime Sanz, Bernhard Kuster, Jean-Marc Rolain, Laurent Debrauwer, Karina B. Xavier, Joao B. Xavier, Carles Ubeda, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Université de Lausanne = University of Lausanne (UNIL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Universidad de Navarra [Pamplona] (UNAV), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Instituto de Salud Carlos III [Madrid] (ISC), Memorial Sloan-Kettering Cancer Institute, Memorial Sloane Kettering Cancer Center [New York], C.U. was supported by the InfectERA-ERANET-Acciones complementarias grant [PCIN-2015-094] from the Spanish Ministerio de Economia y Competitividad and the 7th Research framework program from EU, grants from Conselleria d'Innovacio, Universitats, Ciencia i Societat Digital [AICO/2019/266, CIPROM/2021/053] and a grant from the Spanish MICINN [PID2020-120292RB-I00]. A.D. was supported by a Boehringer Ingelheim Fonds travel grant, and with J.B.X. by grant R01 AI137269/AI/NIAID from the US National Institutes of Health. B.K. was supported by the BMBF FloraStopMRE grant [031L0089]. V.C. was supported by an European Commission grant [MSCA-IF-2018-843183]. J.S. was supported by an InfectERA-ERANET-Acciones complementarias de programacion conjunta internacional grant (AC15/00070) and Proyectos de Investigacion en Salud del Instituto Carlos III (PI18/00280). K.B.X. was supported by FundacAo para a Ciencia e a Tecnologia grant (InfectERA/0004/2015). J.M.R. was supported by ANR FloraStopInfectMRE project., Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and LESUR, Hélène
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Clostridiales ,Multidisciplinary ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Anti-Bacterial Agents ,[SDV] Life Sciences [q-bio] ,Butyrates ,Lactobacillus ,Mice ,Enterobacteriaceae ,Animals ,Prospective Studies - Abstract
Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of hospitalized patients combined with mice experiments, we find that Lactobacillus is key, though not sufficient, to restrict MRE gut colonization. Lactobacillus rhamnosus and murinus increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth through increased butyrate levels and reduced nutrient sources. This mechanism of colonization resistance, an interaction between Lactobacillus spp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions for developing effective probiotics that prevent infections in hospitalized patients.
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- 2021
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