DFG Research Training Group "TJ-Train" (GRK 2318/2)
 Tight junctions and their proteins
Molecular features and actions in health and disease

Project B4     1st period    2nd period

Prof. Dr. Kai Schmidt-Ott1 , Dorothee Günzel2

1Department of Nephrology and Hypertension, Medizinische Hochschule Hannover

2Clinical Physiology / Nutritional Medicine, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin

Transcriptional integration of tight junction biogenesis in 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.

3rd cohort PhD doctoral student

Arnold Tsamo Tetou

  • Tsamo Tetou A, Günzel D (2024) The role of claudins in renal transepithelial transport and kidney disease. Curr. Opin. Nephrol. Hypertens. 33(5): 535-542 (8 pages), doi: 10.1097/mnh.0000000000001003 (°IF 2.2) (Review)

2nd cohort PhD doctoral student

Shuang Cao

1st cohort PhD doctoral student

Janna Leiz
Promotion Sept 30, 2022: "Molecular functions of the transcriptional regulator AP-2 alpha (TFAP2A) in the renal collecting duct".

  • Leiz J*, Hinze C* (*shared first authorship), Boltengagen A, Braeuning C, Kocks C, Rajewsky N, Schmidt-Ott KM (2021) Nuclei isolation from adult mouse kidney for single-nucleus RNA-sequencing. J. Vis. Exp. 175 doi: 10.3791/62901 (IF 1.4)

  • Leiz J, Schmidt-Ott K (2020) Claudins in the renal collecting duct. Int. J. Mol. Sci. 21(1): 221 (11 pages) (Review) [PubMed] [WebPage] [PDF] (IF 5.9)

1st cohort 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