studied Medical Physics at the MLU and at the Ontario Cancer Institute in Toronto, Canada. She obtained her PhD in Physics at the University of Lübeck in 2009. From 2008 to 2010 she worked as a postdoctoral researcher at the Weizmann Institute, Israel, before returning to the MLU to continue her research as a fellow at the Physics Department. Since 2015 she is a project leader in the DFG funded Collaborative Research Center “Polymers under Multiple Constraints” (SFB-TRR102), and since 2018, she works as a tenured staff scientist in the Department of Protein Biochemistry. Her research links life science with polymer physics. One of her main interests is to study the influence of crowding agents on protein structure and structure formation. In particular, IDPs with an extended hydrodynamic radius are expected to undergo compaction under the influence of crowding agents. The aim is to compare the properties of different IDPs in order to investigate the underlying mechanisms. Her main techniques are single-molecule fluorescence spectroscopy and X-ray scattering.
Marcel Köhn
studied Biochemistry at the MLU in Halle where he also obtained his PhD in 2015. Since 2015, he is the scientific coordinator of the RTG 1591 “Posttranscriptional Control of Gene Expression” and since 2016, he is head of an independent junior research group at the Medical Faculty of the MLU. Currently, he conducts research in the field of non-coding RNAs in cardiovascular and neoplastic diseases.
Project within the RTG
Protein and RNA interactions of low-complexity domains and their role in the formation of nuclear bodies
In eukaryotic cells, numerous nuclear bodies (NBs) form through condensation (Boeynaems et al., 2018). NBs are protein-enriched dynamic protein hubs that mediate cellular processes from gene expression to DNA repair and signal transduction (Morimoto & Boerkoel, 2013). Proteins targeted to NBs typically contain intrinsically disordered low-complexity domains (LCDs) that are proposed to drive condensation. Strikingly, the amino acid bias of these LCDs differs depending on the subcellular localization of the proteins, raising the question of whether characteristic LCDs are one possibility to direct NB targeting (Wang et al., 2018). In the current project, we intend to investigate the fundamental principles that preserve the NB’s identity in their cellular environment by focusing on splicing speckles and paraspeckles, which are often located nearby. Although both types of speckles have been described to be liquid-like in terms of the diffusive properties of proteins (Weber, 2019), they likewise display a core-shell or micellar protein-RNA assembly (Yamazaki et al., 2021; Fei et al., 2017). The latter arises from the interplay of favorable sequence-encoded molecular interactions of proteins and RNAs. Notably, co-localized non-coding RNAs (ncRNAs) and RNA-binding proteins (RBPs) regulate a variety of important cellular processes (Morimoto & Boerkoel, 2013) and are often deregulated in pathologies, as seen for splicing speckle components (MALAT1 and SRSF1) and paraspeckle components (NEAT1 and NONO) in cancer (Kessler et al., 2019; Malakar et al., 2017). Hence, a close investigation of the assembly of NBs could also prove useful to understand the role of protein and RNA interaction in the pathological context.
Literature references
Boeynaems, S., Alberti, S., Fawzi, N. L., Mittag, T., Polymenidou, M., Rousseau, F., … & Fuxreiter, M. (2018). Protein phase separation: a new phase in cell biology. Trends in Cell Biology, 28(6), 420-435.
Fei, J., Jadaliha, M., Harmon, T. S., Li, I. T., Hua, B., Hao, Q., … & Ha, T. (2017). Quantitative analysis of multilayer organization of proteins and RNA in nuclear speckles at super resolution. Journal of Cell Science, 130(24), 4180-4192.
Kessler, S. M., Hosseini, K., Hussein, U. K., Kim, K. M., List, M., Schultheiß, C. S., … & Kiemer, A. (2019). Hepatocellular carcinoma and nuclear paraspeckles: induction in chemoresistance and prediction for poor survival. Cellular Physiology and Biochemistry, 52, 787-801.
Lauth, L. M., Voigt, B., Bhatia, T., Machner, L., Balbach, J., & Ott, M. (2022). Heparin promotes rapid fibrillation of the basic parathyroid hormone at physiological pH. FEBS letters, 596, 2928-2939.
Malakar, P., Shilo, A., Mogilevsky, A., Stein, I., Pikarsky, E., Nevo, Y., … & Karni, R. (2017). Long Noncoding RNA MALAT1 Promotes Hepatocellular Carcinoma Development by SRSF1 Upregulation and mTOR ActivationMALAT1 Is a Proto-oncogene in HCC Development. Cancer Research, 77(5), 1155-1167.
Morimoto, M., & Boerkoel, C. F. (2013). The role of nuclear bodies in gene expression and disease. Biology, 2(3), 976-1033.
Wang, J., Choi, J. M., Holehouse, A. S., Lee, H. O., Zhang, X., Jahnel, M., … & Hyman, A. A. (2018). A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell, 174(3), 688-699.
Weber, S. C. (2019). Evidence for and against liquid-liquid phase separation in the nucleus. Non-coding RNA, 5(4), 50.
Yamazaki, T., Yamamoto, T., Yoshino, H., Souquere, S., Nakagawa, S., Pierron, G., & Hirose, T. (2021). Paraspeckles are constructed as block copolymer micelles. The EMBO Journal, 40(12), e107270.
Zorn, P., Misiak, D., Gekle, M., & Köhn, M. (2021). Identification and initial characterization of POLIII-driven transcripts by msRNA-sequencing. RNA Biology, 18(11), 1807-1817.
