Cystic kidney diseases belong to the group of ciliopathies - disorders caused by genetic variants in genes encoding ciliary proteins. Except for autosomal dominant polycystic kidney disease (ADPKD), ciliopathies are rare disorders and syndromes that often exhibit substantial genotypic and clinical overlap. Despite the recognition of the central role of cilia, registered curative therapies remain unavailable, highlighting the urgent need to better understand the underlying pathomechanisms.

This project is based on the hypothesis that a comprehensive and detailed understanding of ciliary composition, its dynamics, and its interactions with other subcellular compartments is essential for elucidating the precise (patho)physiological functions of cilia and their roles in disease development and progression.

Deciphering these mechanisms represents our overarching goal. Specifically, by applying most recently developed proximity labeling technologies to models of ciliopathies, we aim to: (1) gain a comprehensive understanding of the molecular composition and diversity of cilia using kidney organoids; (2) investigate the molecular composition of cilia in vivo; and (3) elucidate protein trafficking between cilia and other subcellular compartments and determine how these processes are altered in disease models of renal ciliopathies.

Ultimately, by defining the molecular inventory and signaling mechanisms of primary cilia in heathy and disease conditions, we aim to contribute to the development of novel disease-modifying therapeutic strategies for ciliopathies.

Figure

Fig.: iAPEX labeling. (A) Two different targeting strategies for ciliary APEX combined with ciliary D-amino acid oxidase (DAAO). (B) Streptavidin-positive cilia upon metabolic labeling with biotin-phenol and D-methionine; L-methionine serves as negative control. (C) Streptavidin-pulldown upon 5HT6-iAPEX labeling

Clinical Relevance

We aim to gain deeper insights into disease mechanisms of ciliopathies. Although individual ciliopathies are rare, they collectively affect many patients. Given their multi-organ involvement this project holds relevance across many medical disciplines. We expect that our findings will refine current pathophysiological concepts and uncover novel mechanisms and targets for future disease-modifying treatments. Results will be shared with the cilia community to promote long-term sustainability.

Approach

Gaining a comprehensive understanding of ciliary molecular composition and diversity using kidney organoids.
1. Analyze the diversity of ciliary composition in kidney organoids.
2. Study the effect of ciliopathy mutations and altered signaling on the ciliary protein composition.
Investigation of the molecular composition of cilia in vivo
1. Integration of the iAPEX system into the Rosa26 locus in mice.
2. Set up labeling protocol with the iAPEX mouse crossed with a Cre-Deleter
To elucidate protein trafficking between cilia and other subcellular compartments and determine how these processes are altered in disease models of renal ciliopathies
1. TransitID to study bidirectional protein trafficking between cilia and other subcellular compartments in mIMCD3 cell lines

Schermer, Bernhard | Ebert, Lena - C 11

Next-Generation Cilia Proximity Labeling to Decipher the Pathomechanisms of Human Ciliopathies

Prof. Dr. Bernhard Schermer

Dr. Lena Ebert

Introduction

Figure

Clinical Relevance

Approach

Lab Website

Affiliations - Bernhard Schermer

Affiliations - Lena Ebert

Publication Record on PubMed - Bernhard Schermer

Publication Record on PubMed - Lena Ebert

Publications generated during 1/2026-12/2028 with CMMC affiliations

2026