Prof. Dr. Bettina Warscheid

AG Biochemie und Funktionelle Proteomik
Institut für Biologie II and
BIOSS Centre for Biological Signalling Studies
Albert-Ludwigs-Universität Freiburg
Schänzlestr. 1
79104 Freiburg            

Tel. +49 (0) 761 203 2690
bettina.warscheid@biologie.uni-freiburg.de    

Project summary:

Dissecting Signaling Complexes and Dynamic Changes of the B cell

B-cell activation as well as hyperactivity and autoimmunity of B cells involve the concerted action of proteins assembled into specific signalling complexes. Single complexes are further integrated into larger protein networks that allow to rapidly transduce signals from the receptor located at the cell surface into the nucleus. Aberrant B-cell receptor (BCR) signalling is often associated with autoimmune diseases and B-cell lymphomas. To obtain a better understanding of B-cell-associated signalling events, we will perform quantitative proteomics studies to dissect signalling complexes in resting and activated B cells. We will delineate the interactomes of the focal adhesion kinase (FAK) and the related proline-rich tyrosine kinase 2 (Pyk2) as well as the BCR/cytoskeleton interactome. Furthermore, we will define the protein complexes and dynamic phosphorylation profiles of cluster of differentiation 22 (CD22) and sialic-acid binding immunoglobulin-like lectin G (Siglec-G), two inhibitory receptors modulating the activity of B lymphocytes. State-of-the-art high resolution mass spectrometry (MS) will further be used to identify chaperone-mediated autophagy substrates in B cells and to study posttranslational modifications of B-cell-associated signalling factors beyond phosphorylation. A pulsed stable isotope labelling with amino acids (SILAC) approach will be employed to identify miR-148a targets in B cells. Moreover, we will develop a label-free MS method to perform large-scale quantitative proteomics of primary B cells. We will use this strategy to reveal how signal transducer and activator of transcription 6 (STAT6) regulates the murine B-cell proteome following the infection of mice with Nippostrongylus brasiliensis. Through integration of large-scale quantitative proteome and transcriptome data, we expect to expand our knowledge about ill-defined processes involved in germinal centre formation following helminth infection. Proteomics studies will be performed in close cooperation with several groups (e.g. P02, P03, P04, P05, P09, P20) in the TRR130. 

Publications P C02:

Meyer, S.J., Böser, A., Korn, M., Koller, C., Bertocci, B., Reimann, R., Warscheid, B., and Nitschke, L. (2020). Cullin 3 Is crucial for pro-B cell proliferation, interacts with CD22, and controls CD22 internalization on B cells. J. Immunol. 204, 3360-3374.

Reimann, L.* Schwäble, A.N.*, Fricke, A., Muehlhaeuser, W.W.D., Leber, Y., Lohanadan, K., Puchinger, M., Schäuble, S., Fässler, E., Wiese, H., Reichenbach, C., Knapp, B., Peikert, C.D., Drepper, F., Hahn, U., Kreutz, C., van der Ven, P.F.M., Radziwill, G., Djinović-Carugo, K., Fürst, D.O., and Warscheid, B. (2020). Phosphoproteomics identifies dual-site phosphorylation in an extended basophilic motif regulating FILIP1-mediated degradation of filamin-C. Commun. Biol. 3, 253.   * first authors.

Hörner, M.*, Eble, J.*, Yousefi, S.O.*, Schwarz, J.*, Warscheid, B., Weber, W., and Schamel, W.W. (2019). Light-controlled affinity purification of protein complexes exemplified by the resting ZAP70 interactome. Front. Immunol. 10, 226.   * first authors

Topf, U.*, Suppanz, I.*, Samluk, L., Wrobel, L., Böser, A., Sakowska, P., Knapp, B., Pietrzyk, M.K., Chacinska, A., and Warscheid, B. (2018). Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species. Nat.Commun. 9, 324.   * first authors

Mokada-Gopal, L., Boeser, A., Drepper, F., Lehmann, C., Dudziak, D., Warscheid, B., and Voehringer, D. (2017). Identification of novel STAT6-regulated proteins in mouse B cells by comparative transcriptome and proteome analysis. J. Immunol. 198, 3737-3745.

Dolezal, E., Infantino, S., Drepper, F., Börsig, T., Wossning, T., Warscheid, B., Tarlinton, D., Jumaa, H., Medgyesi, D., and Reth, M. (2017). The BTG2/PRMT1 module limits pre-B cell expansion by regulating the CDK4/Cyclin D3 complex. Nat. Immunol. 18, 911-920.

Ruf, S., Heberle, A.M., Langelaar-Makkinje, M., Gelino, S., Wilkinson, D., Gerbeth, G., Schwarz, J.J., Holzwarth, B., Warscheid, B., Meisinger, C., van Vugt, M.A., Baumeister, R., Hansen, M, and Thedieck, K. (2017). PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy. Autophagy 13, 486-505.

Dalle Pezze, P., Ruf, S., Sonntag, A.G., Langelaar-Makkinje, M., Hall, P., Heberle, A.M., Navas, P.R., van Eunen, K., Tölle, R.C., Schwarz, J.J., Wiese, H., Warscheid, B., Deitersen, J., Storck, B., Fäßler, E., Schäuble, S., Hahn, U., Horvatovich, P., Shanley, D.P., and K. Thedieck (2016). A systems study on amino acid stimulation reveals concurrent activation of AMPK and mTOR converging on ULK1 and autophagy. Nat Commun in press.

Hannemann, L., Suppanz I., Ba, Q., MacInnes, K., Drepper, F., Warscheid, B., and Koch, H.-G. (2016). Redox-activation of the universally conserved ATPase YchF by thioredoxin 1, Antioxid Redox Signal, 24, 141-156.

Fischer, A., Brummer, T., Warscheid, B., and Radziwill, G. (2015). Differential tyrosine phosphorylation controls the function of CNK1 as a molecular switch in signal transduction, Biochim Biophys Acta 1853, 2847-55.

Hünten, S., Kaller, M., Drepper, F., Oeljeklaus, S., Bonfert, T., Ehrhart, F., Dueck, A., Eichner, N., Friedel, C., Meister, G., Zimmer, R., Warscheid, B., and Hermeking, H. (2015). p53-regulated networks of protein, mRNA, miRNA and lncRNA expression revealed by integrated pSILAC and NGS analyses, Mol Cell Proteomics 14, 2609-2629.