Two SNSF-funded PhD student positions
Mechanisms of Inherited Kidney Disorders Group
Institute of Physiology, University of Zurich
The group “Mechanisms of Inherited Kidney Disorders” co-led by Prof. Olivier Devuyst and Dr. Alessandro Luciani is located at the Institute of Physiology, at the University of Zurich in Switzerland.
Our research primarily focuses on unravelling the fundamental mechanisms that underlie rare inherited metabolic disorders, resulting in proximal tubulopathy and the development of chronic kidney disease (CKD) – one of the fastest growing disease worldwide and a significant public health burden. Our aim is to gain mechanistic knowledge to advance therapeutic strategies addressing the unmet medical needs of individuals affected by rare, severe chronic kidney diseases.
Our involvement in Swiss and European networks has allowed us to develop our projects leveraging genome, transcriptome, proteome, and metabolome analyses. This includes genome-wide association studies (GWAS); the use of genetically modified and humanized animal models; and cutting-edge imaging techniques; cell- and organelle-based function assays; and disease-relevant screening technologies in translation with studies of human tubular disorders collected at the European level. Additionally, our group is at the forefront of developing physiologically-relevant cellular systems, such as primary cultures from micro-dissected nephron segments, and harnessing the power of artificial intelligence (AI) engines and machine learning tools for drug discovery and therapeutic development. We have established an innovative (3R compliant) zebrafish-based platform for high-throughput screens and biochemical profiling, adapted for microsamples, which can be integrated with clinical studies or GWAS.
The proximity and strong collaborations between our research lab, the adjacent institutes, technology platforms, medical and science faculties, university hospitals, and research groups of the ETH Zurich create a highly dynamic environment, which is particularly suited for ambitious students who aspire to pursue a PhD degree and an academic career.
Project: Unlocking mechanisms and therapeutic paradigms for rare inherited diseases
Inherited defects in lysosome-residing proteins can lead to proximal tubulopathy and kidney disease. Recessive mutations in CTNS, the gene encoding cystinosin/CTNS, cause cystinosis, a lysosomal storage disease characterized by early and severe dysfunction of kidney tubular epithelial cells, progressing towards chronic kidney disease (CKD) and life-threatening complications.
Using cystinosis as a paradigm of lysosome dysfunction causing proximal tubulopathy and kidney disease, the project aims to dissect the biological roles of lysosomes in the context of homeostasis, kidney disease, and therapeutic discovery.
The applicants will combine preclinical disease models (mouse, rat, and zebrafish), physiologically-relevant cell systems, cell-and lysosome-based function assays, and disease-relevant screening technologies (i) to decipher how the lysosome direct cell fate determination in the kidney tubule epithelium; and to (ii) dissect factors and mechanisms of lysosomal reformation and their roles in normal and diseased cells. By synergizing prior knowledge-based approaches and artificial intelligence (AI)-powered engine with a cross-species screening and validation workflow, the applicant will rank and prioritize actionable drug targets addressing dysregulated homeostasis in cystinosis. Our ultimate goal is to expedite the effective translation of therapeutic agents from preclinical systems to clinical benefits for individuals with cystinosis and other lysosome-related diseases.
* Selected publications – relevant for the project: Keller S et al. Kidney International 2023, in press; Luciani A & Devuyst O 2023, 1-3; Berquez M et al. Nat Commun. 2023, 14: 3994; Krohn P et al. Hum Mol Gen. 2022, 31: 2262-2278; Berquez et al. JASN 2021, 32: 1265-1267; Berquez M et al. Kidney International 2020, 98: 883-896; Luciani A, Devuyst O. Autophagy. 2020, 16 :1159-1161 ; De Leo M et al. JASN 2020, 31 : 1522-1537 ; Luciani A et al. Nat Commun. 2020, 11 : 970 ; Chen Z, et al. Kidney Int. 2020, 97 :1150-1163 ; Festa BP et al. Nat Commun. 2018, 9:161; Luciani A, et al. Autophagy 2018, 14 :1157-1159 ; De Matteis MA et al. Nat Rev Nephrol. 2017, 13 : 455-470 ; Gabriel SS et al. Kidney Int. 2017, 91 : 842-855 ; De Leo MG et al. Nat Cell Biol. 2016, 18 : 839-850 ; Terryn S et al. Kidney Int. 2016, 89 :1075-1089 ; Prange JA et al. Pflugers Arch. 2016, 468:739-50; Luciani A et al. J Am Soc Nephrol. 2016, 27:2049-61; Devuyst O & Luciani A. J Physiol. 2015, 593:4151-64; Luciani A. et al. Autophagy 2012, 8 : 1657-1672; Luciani A et al. Nat Cell Biol. 2010, 12: 863-875; Luciani A et al. Gut 2010, 59: 311-319; Luciani et al. Journal of Immunology 2009, 183: 2775-2784.
This project will be integrated into the PhD program at the Life Science Zurich Graduate School and will be part of the University Research Priority Program ITINERARE (UZH) – Innovative Therapies in Rare Diseases.
We are actively seeking for:
• Outstanding graduates who are enthusiastic about exploring biological questions that may have therapeutic applications.
• An MSc (or equivalent) with a solid background in biochemistry, cell biology, life sciences, systems biology, biotechnology, or a related discipline.
• Background in lysosome biology, autophagy, kidney physiology, and rare inherited metabolic diseases.
• Experience in cell and molecular biology, biochemistry, and light microscopy techniques, handling and working with rodent models is a significant asset.
• Creative, enthusiastic, critical thinkers, and who thrive in a collaborative team environment.
• Excellent oral and written communication skills in English are essential.
We offer a first-class research environment, focused on a translational research with high medical relevance; access to technological platforms (phenotyping, advanced light microscopy techniques, physiology, and functional genomics); multiple interactions and learning exchange within the University and Academic Hospital in Zurich; networking and recognition in the field of cell biology, rare genetic diseases, and drug discovery.
The salary of this position is according to SNSF regulations for up to 4 years.
Applications should include a cover letter, a full CV, scientific interests and research experience, and the names and addresses of two referees to: email@example.com
Enquiries about the position to: firstname.lastname@example.org
Application deadline: November 30, 2023
Preferred start dates: January through March 2024