Chromosome Dynamics and Hematopoietic Cell Biology
Previous and Current Research
My lab focuses on two major areas, (1) Chromatin dynamics and DNA recombination, and their contribution to genome integrity and cell survival; and (2) the regulation of B cell and mast cell activation through novel signaling networks.
The first project aims at understanding the contribution of SMC (structural maintenance of chromosomes) proteins and their complexes to essential processes in mitosis and meiosis such as sister chromatid cohesion and segregation, DNA recombination and repair, chromosome structure and behaviour. We were first to isolate mammalian SMC proteins and to implicate them in repair of certain DNA damage. We now try to determine the role and mechanisms of SMC complexes to DNA repair. In our studies on germ cells, we identified a novel SMC protein that in a mouse model turned out to be essential for meotic sister chromatid cohesion, telomere movements, and recombination. Our goal in this area is to elucidate the function of SMC complexes in male and female meiosis, and their contributions to avoiding aneuploidies such as the frequent trisomie syndromes in humans. An additional area of interest is the development of germ cells from stem cells.
In our signaling project we try to understand how B cells get induced to switch to expression of specific immunoglobulin isotypes such as IgE, which is key to the allergic reaction, and how these cells migrate, interact with each other and with other cell types. Similarly, we strive to understand how mast cells become activated, degranulate – another reaction linked to the allergic response – , migrate, and contribute to the immune responses. Our identification of a key signaling protein acting in these pathways, SWAP-70, provides a novel entry into these areas.
Future Projects and Goals
In both of our research areas we use integrated approaches, which include a wide range of techniques like biochemical, cellular, genetic, and organismal methods, to deepen our understanding of central processes in mammalian biology, which are highly significant for human health. Thus, we will develop additional mouse models in both areas, will design and use further molecular assays, and attempt to establish innovative stem cell-based systems to address functional and mechanistic problems. The immediate focus is on the SMC proteins and their high-molecular weight complexes in mitosis and meiosis, and on SWAP-70 and related proteins in the hematopietic cell area.
Methodological and Technical Expertise
- Mammalian spermatocyte and oocyte methods including oocyte injection and chromosome analysis
- Large variety of immunological methods addressing mammalian lymphoid and myeloid cells
- Analysis of F-actin cytoskeletal dynamics, integrin activity, cell migration and other cell biology parameters
- Protein biochemistry methods
- Analysis of DNA recombination, DNA repair, DNA binding proteins
C. Adelfalk, Janschek, J., Revenkova, E., Blei, C., Liebe, B., Göb, E., Alsheimer, M., Benavente, R., de Boer, E., Novak, I., Höög, C., Scherthan, H., and R. Jessberger
Cohesin SMC1b protects telomeres in meiocytes.
J. Cell. Biol., 187, 185-199. (2009)
A. Vasileva, D. Tiedau, A. Firooznia, T. Müller-Reichert, and R. Jessberger
Tudor domain protein Tdrd6 is required for spermiogenesis, chromatoid body architecture and regulation of miRNA expression.
Current Biology, 19, 630-639. (2009)
C. Ocana-Morgner, Wahren C, and R. Jessberger
SWAP-70 regulates RhoA/RhoB-dependent MHCII surface localization in dendritic cells.
Blood. 113, 1464-1482. (2008)
G. Pearce, V. Angeli, G. J. Randolph, T. Junt, U. v. Andrian, H. J. Schnittler, and R. Jessberger
Signaling protein SWAP-70 is required for efficient B cell homing to lymphoid organs.
Nature Immunology 7, 827-834. (2006)
E. Revenkova, M. Eijpe, C. Heyting, C. A. Hodges, P. A. Hunt, B. Liebe, H. Scherthan and R. Jessberger
SMC1b is Required for Meiotic Chromosome Dynamics, Sister Chromatid Cohesion, and DNA Recombination.
Nature Cell Biology, 6, 555-562. (2004)