129 zoekresultaten voor “antibiotic resistance” in de Publieke website
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Search and rescue: tackling antibiotic resistance with chemistry
With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.
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Structural characterization of bacterial proteins involved in antibiotic resistance and peptidoglycan biosynthesis
This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.
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Brick in the Wall: The role of the actinobacterial cell wall in antibiotic resistance, phylogeny and development
Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle.
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New polymyxin antibiotics for old problems: addressing nephrotoxicity and resistance
Polymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug resistant Gram-negative bacteria.In this thesis, we describe the development and synthesis of analogues…
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Next generation bacitracin: reimagining a classic antibiotic
Given the accelerating appearance of antimicrobial resistance, there is an urgent need for more fundamental research into novel antibiotic strategies. The work in this thesis helps to address this global problem by developing new antibiotic compounds, inspired by the antibacterial mechanisms of the…
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Synthesis of Ribitol Phosphate based Wall Teichoic acids
Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.
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Next generation lipopeptide antibiotics
This thesis describes the evaluation of novel natural products with antibacterial activity enabled by total chemical synthesis.
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The Ecology and Evolution of Microbial Warfare in Streptomyces
The soil-dwelling, filamentous bacteria of the genus Streptomyces are renowned for their production of useful secondary metabolites including antibiotics. The work described in this thesis provides new insights on the role and regulation of antibiotic production and resistance in these bacteria.
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Semisynthetic glycopeptide antibiotics
Vancomycin is a last-resort antibiotic for the treatment of many Gram-positive bacterial infections, while remaining inactive against Gram-negative strains.
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Discovery of antibiotics and their targets in multidrug-resistant bacteria
Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.
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Quantitative pharmacological modelling for optimizing treatment of sepsis
Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…
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Antibiotic Discovery: From mechanistic studies to target ID
The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.
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Mechanisms and consequences of horizontal gene transfer in cell wall-deficient cells of Kitasatospora viridifaciens
The bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and hyperosmotic conditions, can induce bacteria to shift to a wall-deficient state. It is unknown whether the lack of…
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Aquatic eDNA: Beyond Species Presence
As a non-invasive genetic method, eDNA based approaches have become an important component of ecologists' and environmental managers' toolkits for biomonitoring in conservation and an increasingly important source of ecological knowledge.
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Diagnosis and treatment of obese children with insulin resistance
Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst
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Environmental and metabolomic study of antibiotic production by actinomycetes
Promotor: Prof.dr. G.P. van Wezel
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Anthracycline biosynthesis in Streptomyces: engineering, resistance and antimicrobial activity
Actinobacteria are well known for the production of bioactive natural products, many of which have applications in the fields of human, animal and plant health. Subject of this thesis are the anthracyclines, glycosylated aromatic polyketides with potent anticancer activity.
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Statistical learning for complex data to enable precision medicine strategies
Explaining treatment response variability between and within patients can support treatment and dosing optimization, to improve treatment of individual patients.
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Thrips resistance in Gladiolus: an eco-metabolomic approach
Breeding for resistance becomes more and more important because we want to reduce the use of pesticides. A fast and cheap alternative can be to make use of morphological or chemical markers.
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Cancer chess: molecular insights into PARP inhibitor resistance
The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…
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Discovery of novel Antibiotics from Actinomycetes by Integrated Metabolomics & Genomics Approaches
Promotor: G.P. van Wezel, Co-promotor: Y.H. Choi
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Signalling pathways that control development and antibiotic production in streptomyces
Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments.
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Group benefits from genomic instability: a tale of antibiotic warriors in Streptomyces
Streptomyces are filamentous bacteria that produce more than two-thirds of known antibiotics.
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Impact of plant hormones on growth and development of actinobacteria
Plants are colonized by an astounding number of microorganisms that can provide different life-support functions, including nutrient acquisition and protection against (a)biotic stresses like drought or pathogen attack.
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Using mouse models to uncover genes driving tumorigenesis and therapy resistance in human breast cancer
To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies.
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Evolution of Molecular Resistance to Snake Venom α-Neurotoxins in Vertebrates
We have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins of many venomous snakes binds to this receptor in its location at the neuromuscular junction in all ve…
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Shaping the pharmacokinetic landscape for renally cleared antibiotics in obesity
The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.
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Multi-omics studies of the control of growth and antibiotic production of Streptomyces
Actinobacteria are Gram-positive bacteria that have a complex multicellular life cycle and are well known for their ability to produce a wide range of bioactive natural products (NPs).
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Resistance to PARP inhibition by DNA damage response alterations in BRCA1/2-deficient tumors
Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.
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Political Muslims: Understanding Youth Resistance in a Global Context
An interdisciplinary collection of the best international scholarship on Muslim youth.
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insertional mutagenesis to identify breast cancer drivers and therapy resistance genes in mice
In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.
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Potentiation of Gram-positive specific antibiotics against Gram-negative bacteria through outer membrane disruption
Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.
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Evolutionary adaptability of β-lactamase: a study of inhibitor susceptibility in various model systems
β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…
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Marcellus Ubbink
Wiskunde en Natuurwetenschappen
m.ubbink@chem.leidenuniv.nl | +31 71 527 4628
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environmental factors determining heterogeneity in preservation stress resistance of Aspergillus niger conidia
Fungal food spoilage often starts with a contamination with spores. Experimental data strongly indicate the existence of subpopulations of spores with different levels of resistance to preservation methods.
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Targeting electron transport chain in Listeria monocytogenes for novel antibiotic development
Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)
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Exploring the chemical space of post-translationally modified peptides in Streptomyces with machine learning
The ongoing increase in antimicrobial resistance combined with the low discovery of novel antibiotics is a serious threat to our health care.
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reduced mycelial heterogeneity for improved production of enzymes and antibiotics
Hoe kan de techniek van cell wall engineering worden ingezet zodat de industrie streptomyceten beter kunnen verwerken tot nieuwe antibiotica?
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Onderzoekers gaan de strijd aan met antibioticaresistente bacteriën
Wanneer een bacterie resistenter wordt voor het ene antibioticum, wordt het soms gevoeliger voor een ander. Om deze wisselwerking beter te begrijpen, brachten onderzoekers van het Instituut Biologie Leiden (IBL) en het Leiden Academic Centre for Drug Research (LACDR) onder leiding van Daniel Rozen en…
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Ecology and genomics of Actinobacteria and their specialised metabolism
Filamentous Actinobacteria, such as Streptomyces, produce a plethora of chemically diverse bioactive metabolites that have found applications across medicine, agriculture and biotechnology.
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Targeted Therapy for Triple-Negative Breast Cancer
The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.
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Comorbidities, complications and treatment of childhood obesity
Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens.
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Publicatie: Artistic Research in Music: Discipline and Resistance - Artists and Researchers at the Orpheus Institute
Publicatie boek 'Artistic Research in Music: Discipline and Resistance' markeert 20-jarig jubileum Orpheus Instituut.
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Uncovering vulnerabilities in triple-negative breast cancer
Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.
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Disrupting the transcriptional machinery to combat triple-negative breast cancer
Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.
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Functional xylem anatomy: intra and interspecific variation in stems of herbaceous and woody species
My PhD thesis investigates the ecological significance of resistance against drought-induced air bubble formation inside the water conduits of plants (embolism), and the plasticity and functional aspects of stem anatomical traits in woody and herbaceous species.
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Exploring and exploiting the mechanism of mycelial pellet formation by Streptomyces
Promotor: G.P. van Wezel
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Towards a system-based pharmacology approach to predict developmental changes in renal drug clearance in children
Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)
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Disentangling drought-responsive traits with focus on Arabidopsis
In recent decades, climate change has led to more frequent and severe drought events, causing serious consequences such as increased forest mortality and significant crop yield losses. Understanding how drought affects plants, especially economically important herbaceous species, is crucial for predicting…
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Growth and Transport properties of (Rare Earth)TiO3 / SrTiO3 interfaces
This thesis presents the results of a study on the interfaces of insulating oxides with and without the insertion of a magnetic layer.