Playing in Traffic: Novel Signaling and Trafficking Mechanisms in Epithelial Cells
Our group is interested in embryonic renal development and disease. Which molecular and structural events lead to the formation of a functioning kidney? How these events are disrupted in hereditary renal diseases is a major focus of our work.
How do renal tubules form?
The kidney is a highly complex, but well-structured organ. We are especially interested in how renal tubules assume and maintain their shape. Using the embryonic kidney of Xenopus, we found that extensive cell migration and rearrangement occurs during tubule formation. Direction to these movements is provided by distinct molecular signals during renal morphogenesis.
What are the molecular causes of hereditary renal disease?
A number of genetic renal diseases can occur early in life and have severe consequences for the affected patients. We try to understand how defective molecules lead to disrupted structural renal development, for example in congenital anomalies of the kidney and urinary tract (CAKUT). Together with a large international team, we identified a novel ciliopathy gene that causes the rare cystic kidney disease nephronophthisis, when mutated.
- Lienkamp S et al., Inversin relays Frizzled-8 signals to promote proximal pronephros development. PNAS 107, 20388-20393 (2010).
- Hoff S, et al., ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nature genetics 45, 951-956 (2013).
How is the identity of tubule cells controlled? - Direct reprogramming to tubule cells
We recently reprogrammed fibroblasts to induced renal epithelial tubule cells (iRECs) using only 4 transcription factors. This type of cell conversion did not depend on pluripotency (as in iPS reprogramming), but was the first example of the direct cell type conversion of fibroblasts to a differentiated renal cell type. This technique may be useful to generate novel in vitro models for human genetic kidney diseases or could be used for renal toxicity testing of new drugs. It also sheds light on how the identity of tubule cells is controlled on a transcriptional level.
- Kaminski M, et el.. Direct Reprogramming of Fibroblasts into Renal Tubular Epithelial Cells by Defined Transcription Factors. Nature Cell Biology 18, 1269-1280 (2016).
Fascinating datasets, but mostly hidden in the supplements.
Biology is getting increasingly quantitative. But despite the flood of excellent data generated by screens, NGS, proteomics and other approaches, much of it is hidden in supplementary data tables, not computer readable, not standardized, and not searchable.
Therefore, we developed a platform to search multiple meaningful datasets for a gene of interest: DormantData.org
This database currently contains >100 hand-curated gene lists, which we found interesting, and links to the original publications. The data originates from various technical approaches (genome wide screens, proteomics, genetic data, differential expression, ...) across multiple species. All datasets were matched to the human (HGNC) gene symbol for easy retrieval. Have a look and see, where in the supplements your favourite gene is hiding.
Science is Teamwork
We regularly accept medical students for their work on a thesis (Doktorarbeit) in our lab. Beginning in February or September of each year, the experimental work will require 8 month of dedicated time in the lab. We offer an introductory course in general molecular biology techniques at the beginning of each term and are dedicated to excellent support and supervision. We also participate in the MOTI-VATE program, which offers support for medical students with a strong interest in research. If you are interested to join and would like to know more about current medical thesis projects, please email soeren.lienkamp(at)uniklinik-freiburg.de.
We are lucky to be embedded in the inspiring research environment of the Department of Nephrology. We are also thankful to participate in and benefit from Institutions such as the Excellence Cluster BIOSS, the Spemann Graduate School of Biology and Medicine (SGBM), the Live Imaging Center Freiburg, or the SFB 1140-KIDGEM.