Institute of Physiology

PhD position in the group "Mechanisms of Inherited Kidney Disorders"

The group "Mechanisms of Inherited Kidney Disorders" led by Prof. Dr. med. Olivier Devuyst is located on the Irchel campus at the University of Zurich in Zurich, Switzerland. The close interactions between the research lab, the surrounding institutes and technology platforms from the medical and science faculties, the university hospitals, and the research groups of the ETH Zurich represent a major strength creating a highly dynamic environment.
Our group is investigating the fundamental mechanisms that underlie congenital kidney disorders, causing chronic kidney disease (CKD) – one of the fastest growing disease worldwide and a major public health burden.
Based on a cell- and molecular biology approach applied on mouse and cellular systems, complemented by studies on population and patient material, and by mouse and human genetics, we investigate the mechanisms of normal and defective transport systems in specific epithelial cells. These studies are focusing on inherited kidney disorders affecting various nephron segments, including polycystic kidney disease. Insights obtained through these investigations are relevant for common conditions such as blood pressure regulation, kidney stones, urinary tract infection, progression of CKD, and cardiovascular complications. Our ultimate goal is to gain mechanistic knowledge to develop novel therapies and biomarkers susceptible to improve the care for patients with genetic disorders impacting epithelial cells in the kidney and other organs.
Our participation in Swiss and European networks has allowed us to develop our projects using genome, transcriptome and proteome analyses; genome-wide association studies (GWAS); genetically modified and humanized mice; and cutting-edge imaging techniques, in translation with studies of human tubular disorders collected at the European level. Our group is also developing innovative cell systems (primary cultures from micro-dissected nephron segments, iPS cells, microtissues) as well as a zebrafish platform to perform high-throughput screens and a biochemical profiling platform adapted to microsamples (high-throughput screens coupled to clinical studies or GWAS).

The project
Epithelial cells that line the proximal tubule of the kidney rely on an intertwined ecosystem of membrane trafficking pathways to ensure the reabsorption of a large variety of essential nutrients. To function effectively and to achieve homeostasis, these specialized cells require the sorting and recycling of a wide array of cell surface proteins within the endolysosomal network, including signalling receptors, nutrient transporters, ion channels and polarity markers. Disruption of this sophisticated network of vesicular transport mechanisms leads to proximal tubule dysfunction and kidney disease. However, mechanistically, how the dysregulated endolysosome system triggers proximal tubule dysfunction has remained incompletely understood. Using inherited kidney diseases (i.e. Dent disease, Lowe syndrome and cystinosis) that target various endolysosomal proteins, the aim of the project is to dissect the role of the endolysosome system in kidney health and disease. More specifically, we will combine in vivo genetic modified animals (mouse, rat and zebrafish) and in vitro models with unbiased approaches (i) to decipher the regulatory circuitries governing dynamics and the homeostasis of the endolysosome system; (ii) to characterize the role of these molecular factors in the cellular events leading to kidney tubule dysfunction and disease. Ultimately, integrating systems biology with innovative preclinical models and cell-based screening technologies, we will translate promising preclinical drug candidates into clinics to improve patient care.

Your responsibilities

• Organize annual reporting meetings with the doctoral committee.
• Take part in teaching and practical courses in the subject area as required by the doctoral program.
• Attend continuing education courses as required by the doctoral committee.
• Attend as early as possible advanced courses, colloquia and workshops related to the area of the Student's PhD topic.

Your profile

We are interested in engaged, multi-talented candidates who are enthusiastic about tackling basic biological questions with potential therapeutic applications. This position is particularly suited for applicants with a background in experimental animal models (mouse and/or rat) and/or cell biology. The candidate must demonstrate a capacity to adapt to a new environment and to interact with colleagues. She/he will be supported by a motivated team and technicians.

What we offer

Excellent living conditions and attractive salary in Switzerland; first-class research environment, focused on a translational research with high medical relevance; multiple interactions and international environment within the University and Academic Hospital in Zurich; networking and recognition in the field of rare diseases.

Place of work

Winterthurerstrasse 190, CH-8075 Zurich

Start of employment

October 2020 to January 2021 – to be discussed

Further information

Your application should include a cover letter, a full CV, and the names and addresses of three potential referees.
Enquiries about the position please send to:

Dr. Alessandro Luciani, Senior associate scientist