About the Project
http://www2.mrc-lmb.cam.ac.uk/groups/mschuh/index.html
All animal life starts with the fertilization of an egg. An egg and a sperm fuse and together they form a new genetically unique embryo. However, estimates suggest that 25-70% of human embryos die soon after fertilization because they are chromosomally abnormal. Most of these embryos inherited their abnormalities from the egg: depending on the age of the woman, 10-50% of human eggs are chromosomally abnormal. This high percentage of abnormal eggs results from errors during oocyte maturation, the process by which a diploid oocyte eliminates half of its chromosomes to mature into a fertilisable egg. Chromosome segregation during sperm development is much more reliable because only 1-2% of sperm have an incorrect number of chromosomes. Thus, errors during meiosis in human oocytes are the most common cause of pregnancy loss and genetic diseases such as Down’s syndrome.
Surprisingly, we still know very little about how mammalian oocytes mature into eggs, and it is still unclear why meiosis is so much more error-prone than mitosis.
The aim of the Schuh lab is to understand how mammalian oocytes mature into eggs and how defects during oocyte maturation lead to aneuploidy. To this end, we apply state-of-the-art microscopy techniques (superresolution microscopy, quantitative confocal live cell microscopy, single molecule microscopy and electron microscopy), in vitro reconstitution assays as well as molecular cell biology and biochemical techniques to investigate meiosis in mouse and human oocytes. The successful candidate will be able to choose between several exciting projects that will be discussed on the interview day, all of which pose fascinating opportunities for novel discoveries.
Because errors during oocyte maturation lead to pregnancy loss, birth defects and infertility, this work will not only provide important insights into fundamental cellular mechanisms, but will also have important implications for human health.
References
Clift, D., Schuh, M. (2013). Restarting life: fertilization and the transition from meiosis to mitosis. Nat. Rev. Mol. Cell Biol. 14, 549-62.
Holubcová Z., Howard G., Schuh M. (2013). Vesicles modulate an actin network for asymmetric spindle positioning. Nat. Cell Biol. 15, 937-947.
Cover Story and Research Highlight in Nature Reviews Molecular Cell Biology. Evaluated in Faculty of 1000.
Schuh, M. (2011). An actin-dependent mechanism for long-range vesicle transport. Nat. Cell Biol. 13, 1431-1436.
Cover Story and highlighted by "News and Views" in Nature Cell Biology. Evaluated in Faculty of 1000.
Pfender, S., Kuznetsov, V., Pleiser, S., Kerkhoff, E., Schuh, M. (2011). Spire-type actin nucleators cooperate with formin-2 to drive asymmetric oocyte division. Curr. Biol. 21, 955-960.
Cover Story and Research Highlight in Current Biology.
Schuh, M., and Ellenberg, J. (2008). A new model for asymmetric spindle positioning in live mouse oocytes. Curr. Biol. 18, 1986-92.
Highlighted as Editor’s Choice in Science and featured article in Current Biology.
Schuh, M., and Ellenberg, J. (2007). Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130, 484-498.
Covered by Nature Research Highlights.
Kudo, N.R., Wassmann, K., Anger, M., Schuh, M., Wirth, K.G., Xu, H., Helmhart, W., Kudo, H., McKay, M., Maro, B., Ellenberg, J., de Boer, P. & Nasmyth, K. (2006). Resolution of chiasmata in oocytes requires separase-mediated proteolysis. Cell, 126, 135-146.
We provided the cover picture for this issue of Cell.