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We are recruiting students for the following Ph.D. positions:
Host and microbe: tug-of-war for nutrients
Infectious diseases remain the prime cause of human mortality and nutrient acquisition by pathogenic microbes at the infection site leads to ‘tug-of war’ for essential metal nutrients with the host. To address the largely neglected role of metallophores secreted by critical human pathogens, their physicochemical parameters will be determined. Complexes of new bacterial, mycobacterial, and fungal metallophores with relevant metal ions will be formed in vitro and characterized for specificity, stoichiometry, and stability. Metallophore receptors will be identified, and the intercellular host-pathogen crosstalk will be monitored by quantification of metallophores secreted by microbial consortia and their mammalian hosts. The knowledge of molecular interactomes in the diagnostic assessment of endotracheal aspirates of critically ill patients suffering from superinfections will be applied. The proposed work has the potential to shift the paradigms of microbial pathogenesis and pave the way to novel therapeutic strategies for combatting infections. The PhD student will actively use general analytical chemistry, organic mass spectrometry (in multiple variants), microbiology, and microscopy.
Molecular mechanisms of host pathogen interaction in Lyme disease and Post-treatment Lyme disease syndrome
Lyme disease (LD) is Borrelia bacterium infection treatable by antibiotics. A subset of LD patients experience lingering affections of musculoskeletal and neurological systems, in the scientific literature reported as the post-treatment LD syndrome (PTLDS). Involvement of various Borrelia morphotypes, described in vitro, is intensively discussed. In proposed thesis the pathogen/host interactions will be probed by analyzing metabolomic and metallomic markers of spiral and non-spiral Borrelia forms as well as host immune and non-immune cell responses by measuring selected immune parameters and host-cells metabolome changes using in vitro and in vivo models. Further the analysis of Borrelia metabolomic and metallomic markers in patients suffering of PTLDS-associated complications is proposed. The obtained metabolomic and metallomic data might have the potential to fundamentally alter the view on the diagnosis and potentially also the treatment of LD and might lead to the identification of potentially applicable biomarker/s predicting a patient's individual LD course or PTLD development. The PhD student will actively use general analytical chemistry, clinical mass spectrometry (in multiple variants), microbiology, and microscopy.
Brain neurochemistry in bacterial central nervous system infections
Bacterial central nervous system (CNS) infections may be fast, deadly, and associated with chronic, long-term, or permanent sequelae. Neurochemical and metabolomic bacterial pathogenesis is poorly studied at the region- and cell-specific levels. In the bacterial meningitis /encephalitis model, the CNS-localized cellular, morphological, and compositional changes responding to infection episodes will be defined. In a rat model of treated and untreated CNS infections, the thesis will define the acute and post-infection metabolome impact on brain neuronal signaling at the (sub)regional levels and determine new neuromodulators as predictors of adverse neurological outcomes. Host and pathogen metabolomic biomarkers and neuromodulators characterized in situ will be validated on cerebrospinal fluids collected from patients with CNS infections. To be developed in the thesis, the new bioinformatic platform may define host-pathogen metabolomic biomarkers involved in long-term brain neurodegeneration, improve clinical diagnostic accuracy, and predict bacterial infection-specific neurochemical processes. The PhD student will actively use general analytical chemistry, clinical mass spectrometry (in multiple variants), microbiology, and microscopy.
For these Ph.D. positions, please, write your inquiry to v l h a v l i c @ b i o m e d . c a s . c z
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