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Candidate genes for control of renal function and arterial blood pressure
Switzerland (Swimsa) - University of Zurich, Zurich
Institute of Anatomy
Prof. Johannes Loffing
Prof. Johannes Loffing
Type of Research Project
- Basic science
What is the background of the project?
Arterial hypertension is a major health problem and still one of the leading causes for premature death. Genetic and environmental factors (including an altered dietary ion intake) contribute to the high prevalence of arterial hypertension. The kidneys are central for the control of blood pressure by adapting urinary ion excretion to dietary intake. Consistently, most monogenetic forms of arterial hypertension interfere with the regulation and function of renal ion transport (Rossier et al. Physiology 2017). We recently identified several novel candidate genes for the control of renal function and arterial blood pressure. The precise localization of the expression of these candidate genes along the renal tubular system and the functional role of these genes in the kidney are largely unclear.
What is the aim of the project?
The aim of the project is to characterize the localization of one of the candidate gene products along the renal tubular system and to study its regulation under different functional conditions (e.g. altered dietary salt intake).
What techniques and methods are used?
The project will take advantage of already archived kidney samples from wildtype and gene-modified mice kept on different dietary salt intakes. The available kidney samples will be studied by immunohistochemistry and immunoblotting. Co-immunostainings for the candidate gene product and appropriate nephron marker molecules will allow to establish a detailed cellular and subcellular localization of the protein of interest along the renal tubular system. Immunoblotting will allow to study the regulation of the protein abundance under various functional conditions. The student will get a thorough introduction into the described techniques and will be trained in the detailed microscopical analysis of the kidney.
What is the role of the student?
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will learn and perform the immunohistochemistry, which includes the sectioning of the kidney specimens in a cryostat and the subsequent incubation of the cryosections with the respective antibodies for the detection of the proteins of interest. Subsequently, the student will study the immunostained cryosections under the microscope. Depending on the progress of the work, the student may also learn and perform immunoblotting (Western Blot) experiments, which will include the preparation of the needed solutions, the casting of gels, the electrophoretic separation and transfer followed by the detection of the protein.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
The student will get a thorough training in the used methods and introduction in the microscopical anatomy of the mammalian kidney. The theoretical background of the project will be discussed with the student and appropriate readings (review and original articles) will be provided. The student will be integrated as a visiting fellow in all activities of the research group, which includes lab meetings, seminars, research discussions.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Motivation. Basics in Physiology and Histology are required.
Are there any legal limitations in the student’s involvement
A visa as visiting scholar will be organized.
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months)
- Rossier et al. 2017 (PMID: 28202622) : The Hypertension Pandemic: An Evolutionary Perspective.
- Penton et al. 2015 (PMID: 25559844) : Dietary potassium and the renal control of salt balance and blood pressure.
- Picard et al. 2014 (PMID: 24231659): Protein phosphatase 1 inhibitor-1 deficiency reduces phosphorylation of renal NaCl cotransporter and causes arterial hypotension.
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