Project Details
Projekt
KFO 201: Polycystic Kidney Disease - From Model Organisms to Novel Therapies
Subject Area
Medicine
Term
from 2008 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 58488057
This Clinical Research Unit was formed to bridge the gap between cutting-edge experimental research and optimal patient care. It aims at translating novel experimental findings into new treatments to combat the development and progression of polycystic kidney disease (PKD). The Clinical Research Unit takes advantage of a unique interdisciplinary group of scientists and clinicians that will coordinate their efforts to address three crucial areas of PKD research:
(1) use of model organisms to elucidate the molecular basis of PKD,
(2) analysis of molecular signalling components of PKD and
(3) development of new effective treatment based on a better understanding of PKD. (1) Model organisms of polycystic kidney disease: Many advances in PKD research have originated from work with model organisms. The Clinical Research Unit employs four model organisms (Drosophila, Xenopus, C. elegans, and zebrafish) to complement the traditional rodent models of PKD. These animal models will be used to elucidate evolutionarily conserved signalling pathways of PKD as a basis for novel therapeutic approaches. (2) Signalling in Polycystic Kidney Disease: Defining the PKD signalling pathways will deepen our mechanistic understanding of polycystic kidney disease and provide new therapeutic targets for suppressing cyst formation. A multidisciplinary approach using biochemical, cell biological and physiological studies will be used to investigate the PKD signalling pathway in vivo and in vitro. (3) Therapeutic targets in polycystic kidney disease: Based on their efficacy in animal models of polycystic kidney disease, two drugs are now in clinical trials for PKD, vasopressin-2-receptor antagonists and mTOR inhibitors. However, these experimental medications for treatment of PKD work through mechanisms that are not well understood. We will evaluate current therapeutic approaches, address downstream consequences of deregulated signalling and attempt to improve therapy. All projects are designed for optimal synergy. New approaches to treat polycystic kidney disease rely on a deeper understanding of what goes wrong in cells to drive cyst growth. The projects will elucidate the function of PKD proteins and detail the signalling cascades that control normal renal development. The framework of a Clinical Research Unit was chosen to emphasise the translational aspect of this collaborative effort and to focus the research of all participating groups towards one goal: a cure for this hereditary disease.
(1) use of model organisms to elucidate the molecular basis of PKD,
(2) analysis of molecular signalling components of PKD and
(3) development of new effective treatment based on a better understanding of PKD. (1) Model organisms of polycystic kidney disease: Many advances in PKD research have originated from work with model organisms. The Clinical Research Unit employs four model organisms (Drosophila, Xenopus, C. elegans, and zebrafish) to complement the traditional rodent models of PKD. These animal models will be used to elucidate evolutionarily conserved signalling pathways of PKD as a basis for novel therapeutic approaches. (2) Signalling in Polycystic Kidney Disease: Defining the PKD signalling pathways will deepen our mechanistic understanding of polycystic kidney disease and provide new therapeutic targets for suppressing cyst formation. A multidisciplinary approach using biochemical, cell biological and physiological studies will be used to investigate the PKD signalling pathway in vivo and in vitro. (3) Therapeutic targets in polycystic kidney disease: Based on their efficacy in animal models of polycystic kidney disease, two drugs are now in clinical trials for PKD, vasopressin-2-receptor antagonists and mTOR inhibitors. However, these experimental medications for treatment of PKD work through mechanisms that are not well understood. We will evaluate current therapeutic approaches, address downstream consequences of deregulated signalling and attempt to improve therapy. All projects are designed for optimal synergy. New approaches to treat polycystic kidney disease rely on a deeper understanding of what goes wrong in cells to drive cyst growth. The projects will elucidate the function of PKD proteins and detail the signalling cascades that control normal renal development. The framework of a Clinical Research Unit was chosen to emphasise the translational aspect of this collaborative effort and to focus the research of all participating groups towards one goal: a cure for this hereditary disease.
DFG Programme
Clinical Research Units
Projects
- Characterization of the ciliary flow sensor and its role in epithelial cell polarity (Applicant Kühn, E. Wolfgang )
- Cyst formation in zebrafish (Applicant Kramer-Zucker, Albrecht )
- Identification and functional characterization of new components of TOR signalling in C. elegans (Applicant Neumann-Haefelin, Elke )
- NPHP-related polycystic kidney disease in man and mice (Applicant Omran, Heymut )
- Part B: Signalling in Polycystic Kidney Disease: Wnt signalling in kidney development and disease (Applicant Grosschedl, Rudolf )
- Polycystin-2 signalling in Drosophila melanogaster (Applicant Köttgen, Michael )
- Regulation of ciliogenesis and ciliary disassembly by nephrocystins (Applicants Jung, Manfred ; Walz, Gerd )
- The Role of mTOR dependent and independent signalling pathways for renal tubular cystogenesis (Applicants Huber, Tobias B. ; Reichardt, Wilfried )
- The role of nephronophtisis proteins in motile cilia and renal tubules of Xenopus laevis (Applicant Lienkamp, Soeren )
- Zentralprojekt (Applicant Köttgen, Michael )
Spokesperson
Professor Dr. Gerd Walz
