DFG Research Training Group "TJ-Train" (GRK 2318)
Tight junctions and their proteins
Molecular features and actions in health and disease

Project B4

Prof. Dr. Kai Schmidt-Ott 

Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité - Universitätsmedizin Berlin
and Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft (MDC)
Personal websites: MDC, Charité

Systems level assessment of epithelial barriers in the kidney


Background:
The kidney tubule consists of different epithelial cell types (e. g. proximal tubule, distal tubule, collecting duct epithelial cells), which are characterized by marked differences in their paracellular transport characteristics and their tight junction composition. These epithelia and their barrier characteristics are important for central aspects of kidney function, including blood pressure control and osmoregulation.

PhD project: In this project we aim to comprehensively assess the molecular composition of epithelial barriers within cell types of the kidney using systems biology approaches. The goal will be to produce an atlas of tight junction component-encoding gene expression in the healthy and diseased kidney and to elucidate transcriptional networks associated with their gene expression control.

The project will focus on integration of multi-omics technologies, including single cell transcriptomics and spatially resolved transcriptomics, followed by focused validation experiments. A strong focus will be placed on bioinformatic integration of systems data. The successful candidate will work in an interdisciplinary environment including biologists, computer scientists, mathematicians and clinicians. Initial tasks will include setting up, applying and developing bioinformatics platforms and computational pipelines for the analysis of single cell and spatial transcriptomics and integrated downstream analyses.

The successful candidate will interact within a multidisciplinary environment of biologists, clinicians, computational scientists within the graduate school "TJ-Train" at Charité – Universitätsmedizin Berlin and at the Max-Delbrück Center for Molecular Medicine.

Requirements: Profound background in molecular biology, strong interest in computational data analysis, basic skills in programming (especially the R programming language and in scripting languages such as Perl/Python) are a plus.

PhD doctoral student, 2nd cohort

  • Shuang Cao

PhD doctoral student, 1st cohort

  • Janna Leiz

    • Publications

  • Leiz J, Schmidt-Ott K (2020) Claudins in the renal collecting duct. Int. J. Mol. Sci. 21(1): 221 (11 pages) (°IF 4.6) (Review) [PubMed] [WebPage] [PDF]

MD doctoral student

  • Alexander Holler

Project-related publications

If a paper is not accessible, please mail to .

1. Vukićević T*, Hinze C*, Baltzer S, Himmerkus N, Quintanova C, Zühlke K, Compton F, Ahlborn R, Dema A, Eichhorst J, Wiesner B, Bleich M, Schmidt-Ott KM**, Klussmann E**. Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking. J. Am. Soc. Nephrol. 2019, 30: 795-810. *Co-first, **Corresponding authors.

2. Vigolo E*, Marko L*, Hinze C, Müller DN**, Schmidt-Ullrich R**, Schmidt-Ott KM**. Canonical BMP signaling in tubular cells mediates recovery after acute kidney injury. Kidney Int. 2019, 95:108-122. *Co-first, **Equally contributing principal investigators.

3. Hinze C*, Ruffert J*(Co-first), Walentin K*(Co-first), Himmerkus N, Nikpey E, Tenstad O, Wiig H, Mutig K, Yurtdas ZY, Klein JD, Sands JM, Branchi F, Schumann M, Bachmann S, Bleich M, Schmidt-Ott KM. GRHL2 is required for collecting duct epithelial barrier function and renal osmoregulation. J. Am. Soc. Nephrol. 2018, 29: 857-868.

4. Werth, M.*, Schmidt-Ott, K.M.* (co-first), Leete, T., Qiu, A., Hinze, C., Viltard, M., Paragas, N., Shawber, C.J., Yu, W., Lee, P., Chen, X., Sarkar, A., Mu, W., Rittenberg, A., Lin, C.S., Kitajewski, J., Al-Awqati, Q., Barasch, J. (2017). Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts. eLife 6, e24265.

5. Paragas N*, Kulkarni R*, Werth M*, Schmidt-Ott KM*, Forster C, Deng R, Zhang Q, Singer E, Klose AD, Shen TH, Francis KP, Ray S, Vijayakumar S, Seward S, Bovino ME, Xu K, Takabe Y, Amaral FE, Mohan S, Wax R, Corbin K, Sanna-Cherchi S, Mori K, Johnson L, Nickolas T, D'Agati V, Lin CS, Qiu A, Al-Awqati Q, Ratner AJ, Barasch J. α-Intercalated cells defend the urinary system from bacterial infection. J. Clin. Invest. 2014, 124:2963-76. *Equal contribution.

6. Marko L*, Vigolo E*, Hinze C, Park JK, Roel G, Balogh A, Choi M, Wuebken A, Cording J, Blasig IE, Luft FC, Scheidereit C, Schmidt-Ott KM**, Schmidt-Ullrich R**, Muller DN**. Tubular Epithelial NF-kB Activity Regulates Ischemic AKI. J. Am. Soc. Nephrol. 2016, 27:2658-69. *Co-first, **Equally contributing principal investigators.

7. Aue A, Hinze C, Walentin K, Ruffert J, Yurtdas ZY, Werth M, Chen W, Rabien A, Kilic E, Schulzke JD, Schumann M, Schmidt-Ott KM. A grainyhead-like 2/ovo-like 2 pathway regulates renal epithelial barrier function and lumen expansion. J. Am. Soc. Nephrol. 2015, 26:2704-15.

8. Walentin K, Hinze C, Werth M, Haase N, Varma S, Morell R, Aue A, Pötschke E, Warburton D, Qiu A, Barasch J, Purfürst B, Dieterich C, Popova E, Bader M, Dechend R, Staff AC, Yurtdas ZY, Kilic E, Schmidt-Ott KM. A Grhl2-dependent gene network controls trophoblast branching morphogenesis. Development 2015, 142:1125-36.

9. Werth, M., Walentin, K., Aue, A., Schonheit, J., Wuebken, A., Pode-Shakked, N., Vilianovitch, L., Erdmann, B., Dekel, B., Bader, M., Barasch, J., Rosenbauser, F., Luft, F.C., and Schmidt-Ott, K.M. The transcription factor grainyhead-like 2 (Grhl2) regulates the molecular composition of the epithelial apical junctional complex. Development 137: 3835-3845