Research Topic
The Schuh laboratory (Department of Meiosis) investigates how mammalian eggs develop and why errors in this process lead to infertility, miscarriages, and genetic disorders such as Down syndrome. Our research spans three main areas:

1. Understanding how the oocyte’s cytoskeleton drives meiosis and how defects at the interface between chromosomes and cytoskeletal structures cause aneuploidy and pregnancy loss.
2. Investigating the decline in female fertility with advancing maternal age and developing innovative methods to improve reproductive outcomes.
3. Developing cutting-edge tools and approaches to study meiosis in mammalian oocytes, enabling new discoveries both within our department and across the meiosis research community.

Project
We offer several exciting projects that candidates can choose from, utilizing a wide variety of techniques, including advanced imaging, molecular biology, biochemistry, genetics, and structural biology. For example, we recently expanded into structural studies of oocytes using cryo-electron tomography (Jentoft et al., Cell, 2023). While we welcome applicants with expertise in electron microscopy, we are equally interested in recruiting highly motivated scientists from diverse backgrounds who are excited to tackle ambitious, high-risk, high-reward projects.

Key publications

1. Thomas, C.1, Marx, T. L.1, Penir, S. M., and Schuh, M. (2024)  Ex vivo imaging reveals the spatiotemporal control of ovulation. Nat. Cell Biol. 26, pp. 1997 - 2008 1equal contribution Significance: First videos of the entire process of mammalian ovulation. Uncovers key steps and molecular drivers of ovulation.
2. Harasimov, K. 1, Gorry, R.L. 1, Welp, L.M. 1, Penir, S.M. 1, Horokhovskyi, Y. 1, Cheng, S., Takaoka, K., Stützer, A., Frombach, A.S., Taylor Tavares, A.L., Raabe, M., Haag, S., Saha, D., Grewe, K., Schipper, V., Rizzoli, S.O., Urlaub, H. 2, Liepe, J. 2, and Schuh, M. 2 (2024) The maintenance of oocytes in the mammalian ovary involves extreme protein longevity. Nat. Cell Biol. 26: 1124-1138 1equal contribution 2corresponding authors Significance: Determines longevity and abundance of thousands of proteins in the mouse ovary and mouse oocytes. Shows that proteins in the ovary and oocytes are exceptionally long-lived.
3. Jentoft, IMA, Bäuerlein, FJB, Welp, LM, Cooper, BH, Petrovic, A, Penir, S, Politi, AZ, Horokhovski, Y, Takala, I, Eckel, H, Moltrecht, R, Lénárt, P, Cavazza, T, Liepe, J, Brose, N, Urlaub, H, Fernandez-Busnadiego, R, and Schuh, M (2023) Mammalian oocytes store proteins on cytoplasmic lattices. Cell. 186, 5308–5327. Significance: Shows how mammalian oocytes store proteins for early embryonic development, namely on polymers called cytoplasmic lattes. Includes the first cryo tomography structure from mammalian oocytes.
4. Cheng, S, Altmeppen, G, So, C, Welp, LM, Penir, S, Ruhwedel, T, Menelaou, K, Harasimov, K, Stützer, A, Blayney, M, Elder, K, Möbius, W, Urlaub, H, and Schuh, M (2022) Mammalian oocytes store mRNAs in a mitochondria-associated membrane less compartment. Science. 378 (6617), eabq4835, doi: 10.1126/science.abq4835  Significance: Shows how mammalian oocytes store mRNA for meiosis and early embryonic development, namely in a mitochondria-associated ribonucleoprotein domain (MARDO).
5. So, C, Menelaou1, K, Uraji, J1 , Harasimov, K, Steyer, A, Seres, B, Bucevičius, J, Lukinavičius, G, Möbius, W, Sibold, C, Tandler-Schneider, A, Eckel, H, Moltrecht, R, Blayney, M, Elder, K, Schuh, M (2022) Mechanism of spindle pole organization and instability in human oocytes Science. Vol 375, Issue 6581 doi: 10.1126/science.abj3944 1equal contribution Significance: Shows how the poles of acentrosomal spindles are focussed in human oocytes, and identifies cause of spindle instability, which leads to human egg aneuploidy.
6. So, C1, Seres, KB1, Steyer, Anna M, Mönnich, E, Clift D, Pejkovska, A, Möbius W, and Schuh, M (2019) A liquid-like spindle domain promotes acentrosomal spindle assembly in mammalian oocytes. Science. 364, eaat9557 doi: 10.1126/science.aat9557 1equal contribution Significance: Identifies a liquid-like spindle pole domain (LISD) at the poles of spindles in mammalian oocytes that is required for spindle assembly.
7. Cavazza, T, Politi, AZ, Aldag, P, Baker, C, Elder, K, Blayney, M, Lucas-Hahn, A, Niemann, H, and Schuh, M (2021) Parental genome unification is highly erroneous in mammalian embryos. Cell. 184, 2860-2877.e22. doi: 10.1016/j.cell.2021.04.013 Significance: Establishes live imaging of bovine embryos as model for human embryos and identifies cause of high aneuploidy in human and bovine zygotes (one cell embryos).
8. Clift D*, McEwan W, Labzin LL, Konieczny V, Mogessie M, James LC*, Schuh M1*. (2017) A method for the acute and rapid degradation of endogenous proteins. Cell. 172, 1-15. (*co-corresponding, 1lead-contact) doi: 10.1016/j.cell.2017.10.033 (Open Access). Significance: Establishes Trim-Away, a method to degrade endogenous proteins without prior modification using antibodies and the ubiquitin ligase Trim21.
9. Mogessie B, Schuh M. (2017) Actin protects mammalian eggs against chromosome segregation errors. Science. 357, eaal1647. doi: 10.1126/science.aal1647(Open Access). Significance: Establishes an essential role for spindle actin in spindle assembly and chromosome segregation in mammalian oocytes.
10. Pfender S, Kuznetsov V, Pasternak M, Santhanam B, Schuh M. (2015) Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes. Nature. 524, 239-242. doi: 10.1038/nature14568 (Open Access). Significance: Establishes a strategy to carry out RNAi screens in mammalian oocytes and identifies new genes essential for meiosis.
11. Holubcová Z, Blayney M, Elder K, Schuh M. (2015) Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes. Science. 348, 1143-1147. doi: 10.1126/science.aaa9529 (Open Access). Significance: First study of meiosis (spindle assembly and chromosome segregation) in live human oocytes. Identifies spindle instability as a cause of aneuploidy in human eggs.