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Lehrstuhl für Zell- und Entwicklungsbiologie

ALSHEIMER LAB

Our current research is mainly focused on the function of nucleocytoplasmic network systems in nuclear shaping and meiotic chromosome dynamics. We are also interested in general regulation of chromosome synapsis and in evolutionary aspects of meiosis

Research synopsis

The defining characteristic of eukaryotes is the sequestration of the genetic material by the nuclear envelope (NE). The NE is composed of two nuclear membranes, nuclear pore complexes and the nuclear lamina, a proteinaceous meshwork that is in intimate contact with the nuclear side of the inner nuclear membrane. Besides its primary role in separating nuclear and cytoplasmic activities, the NE constitutes a most central component of intracellular architecture. It is vitally involved in many fundamental nuclear functions such as dynamic chromatin organization, transcription and replication. Several components of the NE were identified to function as key players in signalling pathways and recent studies evidenced that the NE has a pivotal role in nuclear migration, anchoring and positioning. Furthermore, the NE was demonstrated to be a most crucial determinant for maintaining nuclear morphology and shape and for general nuclear integrity and, beyond, the NE was shown to serve as a kind of rail for telomere driven chromosomal rearrangement during meiotic prophase I. Thus, from the current point of view the nuclear envelope represents more than just a simple barrier, rather it constitutes a multifunctional platform at the very center of fundamental cellular processes.

Research in our lab covers several aspects regarding the function of the nuclear envelope and its components during dynamic reorganization of nuclei. One main focus is set on the role of the nuclear envelope in the evolutionary highly conserved meiotic chromosome dynamics and its impact on genome haploidization. In a second core project we try to figure out the molecular mechanisms underlying the well-directed nuclear shaping during sperm head formation.

Besides this, we are also engaged in analyzing general mechanisms of meiotic chromosome pairing and synapsis. We for example try to understand the specific function of telomere driven bouquet formation. We also study the molecular composition of synaptonemal complexes (SCs) and the regulation of SC assembly and disassembly. Furthermore, we are interested in evolutionary aspects of meiosis, i.e. the evolution of the synaptonemal complex in metazoans.

Recent publications

Levy,Y., Ross, J.A., ... , Alsheimer, M. , ... , Lopez-Otin, C., Kennedy, B.K., Lowe, D.A., and Ochala J. (2018). Prelamin A causes aberrant myonuclear arrangement and results in muscle fiber weakness. JCI Insight 3, e120920. doi: 10.1172/jci.insight.120920

Link, J., Paouneskou, D., ... , Alsheimer, M. , Zetka, M., and Jantsch, V. (2018).Transient and partial nuclear lamina disruption promotes chromosome movement in early meiotic prophase. Dev. Cell 45, 212-225. doi: 10.1016/j.devcel.2018.03.018

Link, J., Benavente, R., and Alsheimer, M. (2016). Analysis of Meiotic Telomere Behavior in the Mouse. Methods Mol. Biol. 1411, 195-208. doi: 10.1007/978-1-4939-3530-7_12

Fraune, J., Brochier-Armanet, C., Alsheimer, M., Volff J.N., Schücker, K., and Benavente, R. (2016). Evolutionary history of the mammalian synaptonemal complex. Chromosoma 125, 355-360. doi: 10.1007/s00412-016-0583-8

Gómez, R., Felipe-Medina, N., Ruiz-Torres, M., Berenguer, I., Viera, A., Pérez, S., Barbero, J.L., Llano, E., Fukuda, T., Alsheimer, M., Pendás, A. M., Losada, A., and Suja, J.A. (2016). Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes. EMBO Rep 17, 695-707. doi: 10.15252/embr.201541060

Pasch, E., Link, J., Beck, C., Scheuerle, S., and Alsheimer, M. (2015). The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility. Biol. Open 4, 1792-1802. doi: 10.1242/bio.015768

Link, J., Jahn, D., and Alsheimer, M. (2015). Structural and functional adaptations of the mammalian nuclear envelope to meet the meiotic requirements. Nucleus 6, 93-101.  doi: 10.1080/19491034.2015.1004941

Viera, A., Alsheimer, M., Gómez, R., Berenguer, I., Ortega, S., Symonds, C.E., Santamaría, D., Benavente, R., and Suja, J.A. (2015). CDK2 regulates nuclear envelope protein dynamics and telomere attachment in mouse meiotic prophase. J. Cell Sci. 128, 88-99. doi: 10.1242/jcs.154922

Fraune, J., Alsheimer, M., Redolfi, J., Brochier-Armanet, C., and Benavente, R. (2014). Protein SYCP2 Is an Ancient Component of the Metazoan Synaptonemal Complex. Cytogenet. Genome Res. 144, 299-305. doi: 10.1159/000381080

Link, J., Leubner, M., Schmitt, J., Göb, E., Benavente, R., Jeang, K.-T., Xu, R., and Alsheimer, M. (2014). Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in mammalian meiotic LINC complex formation and function. PLoS Genet. 10, e1004099. doi: 10.1371/journal.pgen.1004099

(full list of publications)

LINC Complexes in Nuclear Shaping

A hallmark of sperm formation is the highly regulated species-specific shaping of the cell nucleus. We try to understand how germ cell nuclei actually change their specific shape from round to elongate.

The nuclear envelope in meiotic chromosome dynamics

Meiosis depends on an unambiguous assignment of the homologous chromosomes to ensure their proper segregation. We try to understand the specific function of the nuclear envelope during this core process of meiosis.

Evolution of the synaptonemal complex (SC)

Meiosis is highly conserved in eukaryotic evolution. Whether this is also true for the synaptonemal complex (SC) - a vitally important supporting structure - was and still is in dispute. In recent years we found clear evidence for a common origin of the core SC in metazoans.

PEOPLE

Manfred Alsheimer

(Group leader)

alsheimer(at)biozentrum.uni-wuerzburg.de

+49 (0)931 31-84282

Silke Braune

(Technician)

silke.braune(at)biozentrum.uni-wuerzburg.de

+49 (0)931 31-84267

Isabell Köblitz

(Technician)

isabell.koeblitz(at)uni-wuerzburg.de

+49 (0)931 31-89110

Hanna Thoma

(PhD student)

hanna.thoma(at)uni-wuerzburg.de

+49 (0)931 31-89865

Cornelia Heindl

(Technician)

cornelia.heindl(at)uni-wuerzburg.de

+49 (0)931 31-84669

Xenia Malzer

(Bachelor student)

xenia.malzer(at)stud-mail.uni-wuerzburg.de

+49 (0)931 31-94263

Kontakt

Lehrstuhl für Zoologie I - Zell- und Entwicklungsbiologie
Am Hubland
97074 Würzburg

Tel.: +49 931 31-84250
Fax: +49 931 31-84252
E-Mail

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