Bernhard Schermer / Max C Liebau - C 12

The role of the cilia-cell-cycle connection in tissue homeostasis of renal tubular epithelium in acute and chronic kidney diseases

Abstract

Recent groundbreaking work has revealed that mutations in genes encoding proteins localized to primary cilia are causative for a large number of different human diseases, now referred to as ciliopathies. A hallmark of most ciliopathies is the development of cystic kidneys caused by aberrant proliferation of epithelial cells.
Primary cilia are antenna-like organelles that project from the surface of virtually all mammalian cells. In addition to sensory functions cilia are linked to the cell cycle: while ciliogenesis typically occurs in interphase, cilia have to disassemble to allow mitotic re-entry. In this project we hypothesize that the process of ciliary disassembly is of extraordinary importance for tissue homeostasis and repair. This can be ideally studied in the kidney, where tissue homeostasis and repair after damage is mainly driven by resident ciliated epithelial cells making accurately timed and efficient ciliary disassembly indispensable and where cilia are important modulators of proliferation and differentiation as we learned from ciliopathies.
In this project we aim to study the impact of this cilia-cell-cycle-connection in 2D and 3D cell culture models and in vivo. We will address the fundamental but to date unanswered biological question of how cilia by regulating cell cycle re-entry modulate tissue homeostasis and repair. We utilize proteomics and live-imaging technologies in combination with genetic engineering to (1) understand the dynamics of ciliary disassembly during cell cycle progression in healthy cells and cells carrying ciliopathy mutations, and (2) investigate how the cilia-cell cycle connection and its perturbations affect tissue homeostasis and repair in vivo.

Clinical/medical relevance and sustainability in disease understanding

Our project aims to provide novel insights in the understanding of multiple human diseases that display aberrant proliferation rates in affected tissues: In fact, the majority of tissues consist of ciliated cells that have to resorb cilia before cell division. Thus, we expect that our studies will challenge several current pathophysiological concepts in the field of nephrology and beyond, by adding the dysregulated cilia-cell-cycle-connection as a novel disease mechanism and potential therapeutic target to the pathogenesis of many diseases. Ultimately this project has the potential to identify pharmaceutical targets able to interfere with ciliary dynamics in (renal) disease.


Prof. Dr. med. Bernhard Schermer

Dept. II of Internal Medicine

Prof. Dr. med. Bernhard Schermer

Principal Investigator C 12
Executive Board Member

bernhard.schermer@uk-koeln.de

Publications - Bernhard Schermer

Link to PubMed


PD Dr. med. Max C Liebau

Dept. of Children and Adolescent Medicine

PD Dr. med. Max Liebau

Co-Principal Investigator C 12

max.liebau@uk-koeln.de

Publications - Max C Liebau

Link to PubMed

Group Members

Lori Borgal (former PostDoc)
Martyna Brütting (technician)
Claudia Dafinger (PostDoc)
Lena Ebert (PhD candidate)
Laura Frech (MD student)
Rajesh Kumar Gandhirajan(former PostDoc)
Sophie Haumann (Postdoc)
Priyanka Kohli (PhD candidate)
Amrei Mandel (MD student)
Lea Münkner (MD student)
Lukas Schlößer (MD student)
Felix Seelemeyer (MD student)
Gisela Slaats (PostDoc)
Benedikt Walla (MD student)