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Mechanisms of inherited kidney disorders.
Switzerland (Swimsa) - University of Zurich, Zurich
Institute of Physiology
Prof. Olivier Devuyst
Prof. Olivier Devuyst
English, French, German
Type of Research Project
- Basic science
What is the background of the project?
Physiology and transport mechanisms: - Mechanisms and regulation of endocytosis in the proximal tube - Salt and water handling by distal nephron segments - Ontogeny and transcriptional regulation of transport systems - Mechanisms of differentiation in epithelial cells - Genome-wide associations studies for renal function parameters Pathophysiology of inherited kidney disorders: - Mechanisms and consequences of proteinuria - Pathophysiology of inherited forms of chronic interstitial nephritis, including uromodulin-associated kidney disorders - Gitelman syndrome and salt-losing tubulopathies - Clinical and genetic aspects of polycystic kidney and liver diseases Characterisation of mouse models generated by random mutagenesis - Characterisation of urinary biomarkers for tubular disorders
What is the aim of the project?
he studies provide mechanistic knowledge and new therapeutic targets to limit the clinical consequences of tubular disorders and the progression of chronic kidney disease (CKD)
What techniques and methods are used?
- Transgenic mouse and zebrafish models, conditional knock-out, segment-specific invalidation - Immortailzed cell lines and primary cell culture systems developed from micro-dissected nephron segments - Manipulation of gene expression in cell lines and primary cultures - Promoter analysis (in silico, in vitro) - In situ hibridisation, advanced quantitative RT-PCR (Reverse transcription polymerase chain reaction) - Immunoblotting, immunoprecipitation and immohisto-/cytochemistry - Intracellular distribution studies: subcellular fractionation, immunogold, biotinylation - Ontogeny of transporters and regulators - Transport studies in cells and antive tissues - Mouse phenotyping: metabolic cages, special diets, pharmacology interventions - Multisystemic phenotyping: cardiovascular, osmoregulation and thirst - Comprehensive biochemical profiling on dedicated platform optimalized for rodent samples - Development and automation of ELISA(Enzyme-linked Immunosorbent Assay) - Water and soluble transport in mouse model of peritoneal dialysis - Biobanking (all human): end stage kidney samples (200+), kidney biopsies (500+), urine samples from isolated populations (N=6000), peritoneal biopsies (100+) DNA(deoxyribonucleic acid) cohorts: rare inherited kidney disorders (N=200), renal transplant (N=300), peritoneal dialysis (N=800) - High throughput analysis of human plasma and urine samples – GWAS (genome wide association study) - Shared resources though EU-funded EUNEFRON (European Network for the Study on Orphan Nephropathies), Genecure, EUROSPAN and EURenOmics consortia
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
- Learning tasks: sharing knowledge, within fields of cell biology and human disease - Identify a scientific biological problem and formulate a relevant hypothesis - Using adequate methods for the hypothesis - Search for, collect, gather and critically examine scientific information relevant to the subject area - Analyse, critically examine and discuss the gained results and conclusions in relation to the hypothesis and the current understanding of the subject area - Prepare and present both an oral presentation and written scientific report of the project
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Readings of review/articles Team meeting Etam project presentation Lectures/seminars
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report - The student’s name will be mentioned in a future publication - The student will have the opportunity to present the results together with the supervisor at a conference
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Scientific curiosity, interest for lab work, precision and ability to work in team
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Pre-Medical students from the American-British system - Students in biomedical fields
- Uromodulin: from physiology to rare and complex kidney disorders; Devuyst O et al
- The Hypertension Pandemic: An Evolutionary Perspective; Devuyst et al
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