Melina Schuh

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Melina Schuh
Melina Schuh, Direktorin am Max-Planck-Institut fur Multidisziplinare Naturwissenschaften.jpg
Schuh in 2020
Born
Germany
Alma mater
Awards EMBO Gold Medal

Melina Schuh is a German biochemist and Director at the Max Planck Institute for Multidisciplinary Sciences. [1] She is known for her work on meiosis in mammalian oocytes, [2] for her studies on the mechanisms leading to the age-related decline in female fertility, [3] and for the development of the Trim-Away protein depletion method. [4]

Contents

Early life and education

Schuh was born in 1980 in Germany and grew up in Bad Pyrmont. [5] In 2004, she received her diploma in biochemistry from the University of Bayreuth, Germany, where she studied the incorporation of Cenp-A into centromeres in Drosophila embryos with Stefan Heidmann and Christian Lehner. [6]

Career

Melina Schuh did her PhD with Jan Ellenberg at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, where she established methods for high-resolution imaging of meiosis in live mouse oocytes. [3] She used these methods to study the organization and positioning of the spindle in mouse oocytes. [5] [7] [8] In 2009, Schuh became a Group Leader at the MRC Laboratory of Molecular Biology in Cambridge, UK. [9] In 2016, she was appointed Director at the Max Planck Institute for Biophysical Chemistry. [1] In 2022, the Institute merged with the Max Planck Institute for Experimental Medicine to form the Max Planck Institute for Multidisciplinary Sciences.

Schuh's laboratory studies the development and function of mammalian oocytes. They are also investigating the causes of the age-related decline in female fertility. Schuh's work focuses on the process of oocyte division, in which oocytes mature into eggs by extruding half of their chromosomes in a small cell termed the polar body. [10] [11] This requires the spindle apparatus in these cells to be positioned asymmetrically. She discovered a role for proteins that control actin nucleation in the positioning of the spindle. [12] In studying how actin helps position the spindle, she discovered that vesicles carrying specific signals can change the organization and density of actin networks. [13] In addition, her group developed a strategy to perform high-content RNAi screens for meiotic genes in mouse oocytes. [14]

Errors in oocyte division can lead to miscarriage and age-related female infertility. Working with Bourn Hall Clinic, the clinic that first pioneered IVF, Schuh studied human oocyte divisions directly, instead of using mouse oocytes as a model system. She found that human oocytes have a surprisingly slow and error-prone mechanism for assembling the meiotic spindle, [15] increasing the likelihood of segregation errors. She has also investigated the reasons why older mothers have a higher rate of pregnancy loss, and found that oocytes from older mothers have a higher frequency of defects in chromosome architecture. [16] [17]

Her lab developed a method for the acute degradation of endogenous proteins, called Trim-Away, [4] and established essential functions for actin [18] and a liquid-like spindle domain in acentrosomal spindle assembly. [19] Recent work from her lab has identified the cause of spindle instability in human oocytes [20] and an mRNA storage mechanism in mammalian oocytes. [21]

Honors and awards

Related Research Articles

<span class="mw-page-title-main">Centromere</span> Specialized DNA sequence of a chromosome that links a pair of sister chromatids

The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fibers attach to the centromere via the kinetochore.

<span class="mw-page-title-main">Meiosis</span> Cell division producing haploid gametes

Meiosis is a special type of cell division of germ cells and apicomplexans in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately result in four cells with only one copy of each chromosome (haploid). Additionally, prior to the division, genetic material from the paternal and maternal copies of each chromosome is crossed over, creating new combinations of code on each chromosome. Later on, during fertilisation, the haploid cells produced by meiosis from a male and a female will fuse to create a cell with two copies of each chromosome again, the zygote.

<span class="mw-page-title-main">Germ cell</span> Gamete-producing cell

A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

<span class="mw-page-title-main">Aurora kinase B</span> Protein

Aurora kinase B is a protein that functions in the attachment of the mitotic spindle to the centromere.

<span class="mw-page-title-main">BUB1B</span> Protein-coding gene in the species Homo sapiens

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta is an enzyme that in humans is encoded by the BUB1B gene. Also known as BubR1, this protein is recognized for its mitotic roles in the spindle assembly checkpoint (SAC) and kinetochore-microtubule interactions that facilitate chromosome migration and alignment. BubR1 promotes mitotic fidelity and protects against aneuploidy by ensuring proper chromosome segregation between daughter cells. BubR1 is proposed to prevent tumorigenesis.

<span class="mw-page-title-main">Dynactin</span>

Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).

<span class="mw-page-title-main">GPR3</span> Protein

G-protein coupled receptor 3 is a protein that in humans is encoded by the GPR3 gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction.

<span class="mw-page-title-main">CENPA</span> Protein-coding gene in the species Homo sapiens

Centromere protein A, also known as CENPA, is a protein which in humans is encoded by the CENPA gene. CENPA is a histone H3 variant which is the critical factor determining the kinetochore position(s) on each chromosome in most eukaryotes including humans.

<span class="mw-page-title-main">Centromere protein E</span> Centromere- and microtubule-associated protein

Centromere-associated protein E is a protein that in humans is encoded by the CENPE gene.

<span class="mw-page-title-main">CENPH</span> Protein-coding gene in the species Homo sapiens

Centromere protein H is a protein that in humans is encoded by the CENPH gene. It is involved in the assembly of kinetochore proteins, mitotic progression and chromosome segregation.

<span class="mw-page-title-main">Meiotic recombination checkpoint</span>

The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed.

<span class="mw-page-title-main">Arp2/3 complex</span> Macromolecular complex

Arp2/3 complex is a seven-subunit protein complex that plays a major role in the regulation of the actin cytoskeleton. It is a major component of the actin cytoskeleton and is found in most actin cytoskeleton-containing eukaryotic cells. Two of its subunits, the Actin-Related Proteins ARP2 and ARP3, closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70 degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion, phagocytosis, and intracellular motility of lipid vesicles.

<span class="mw-page-title-main">KIF15</span> Protein-coding gene in the species Homo sapiens

Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.

The EMBO Gold Medal is an annual award of the European Molecular Biology Organization (EMBO) given to young scientists for outstanding contributions to the life sciences in Europe. Laureates receive a medal and €10,000 and are invited to receive the award and present their research at the annual EMBO Meeting and to write a review published in The EMBO Journal. Medallists can only be nominated by EMBO Members.

<span class="mw-page-title-main">Robin Allshire</span>

Robin Campbell Allshire is Professor of Chromosome Biology at University of Edinburgh and a Wellcome Trust Principal Research Fellow. His research group at the Wellcome Trust Centre for Cell Biology focuses on the epigenetic mechanisms governing the assembly of specialised domains of chromatin and their transmission through cell division.

Ovum quality is the measure of the ability of an oocyte to achieve successful fertilisation. The quality is determined by the maturity of the oocyte and the cells that it comprises, which are susceptible to various factors which impact quality and thus reproductive success. This is of significance as an embryo's development is more heavily reliant on the oocyte in comparison to the sperm.

Anne Bertolotti is a French biochemist and cell biologist who works as Programme Leader at the MRC Laboratory of Molecular Biology in Cambridge, UK. In 2022 she was appointed Head of the MRC LMB's Neurobiology Division. She is known for her research into the cellular defences against misfolded proteins and the mechanisms underlying their deposition, the molecular problem causative of neurodegenerative diseases.

<span class="mw-page-title-main">M. Madan Babu</span> Indian-American computational biologist

M. Madan Babu is an Indian-American computational biologist and bioinformatician. He is the endowed chair in biological data science and director of the center of excellence for data-driven discovery at St. Jude Children’s Research Hospital. Previously, he served as a programme leader at the MRC Laboratory of Molecular Biology (LMB).

Oocytes are immature egg cells that develop to maturity within a follicle in the ovary. Oocyte abnormalities can occur due to several factors, including premature ovarian insufficiency (POI), other maturation abnormalities, maternal ageing, and mitochondrial abnormalities.

References

  1. 1 2 "Curriculum Vitae". www.mpinat.mpg.de. Retrieved 3 May 2023.
  2. Charalambous, Chloe; Webster, Alexandre; Schuh, Melina (2023). "Aneuploidy in mammalian oocytes and the impact of maternal ageing". Nature Reviews Molecular Cell Biology. 24 (1): 27–44. doi:10.1038/s41580-022-00517-3. ISSN   1471-0080. PMID   36068367. S2CID   252109475.
  3. 1 2 "EMBO Gold Medal 2018 awarded to Marek Basler and Melina Schuh". Embo.org. 16 May 2018.
  4. 1 2 "A Method for the Acute and Rapid Degradation of Endogenous Proteins".
  5. 1 2 Sedwick, Caitlin (31 March 2014). "Melina Schuh: First comes the egg". J Cell Biol. 204 (7): 1080–1081. doi:10.1083/jcb.2047pi. ISSN   0021-9525. PMC   3971742 . PMID   24687276.
  6. Schuh, Melina; Lehner, Christian F.; Heidmann, Stefan (6 February 2007). "Incorporation of Drosophila CID/CENP-A and CENP-C into Centromeres during Early Embryonic Anaphase". Current Biology. 17 (3): 237–243. doi: 10.1016/j.cub.2006.11.051 . ISSN   0960-9822. PMID   17222555. S2CID   17907028.
  7. Schuh, Melina; Ellenberg, Jan (10 August 2007). "Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes". Cell. 130 (3): 484–498. doi: 10.1016/j.cell.2007.06.025 . ISSN   0092-8674. PMID   17693257.
  8. Schuh, Melina; Ellenberg, Jan (23 December 2008). "A new model for asymmetric spindle positioning in mouse oocytes". Current Biology. 18 (24): 1986–1992. doi:10.1016/j.cub.2008.11.022. hdl: 11858/00-001M-0000-002A-2372-5 . ISSN   1879-0445. PMID   19062278. S2CID   18672283.
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  12. Pfender, Sybille; Kuznetsov, Vitaliy; Pleiser, Sandra; Kerkhoff, Eugen; Schuh, Melina (7 June 2011). "Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric oocyte division". Current Biology. 21 (11): 955–960. doi:10.1016/j.cub.2011.04.029. ISSN   1879-0445. PMC   3128265 . PMID   21620703.
  13. Holubcová, Zuzana; Howard, Gillian; Schuh, Melina (2013). "Vesicles modulate an actin network for asymmetric spindle positioning". Nature Cell Biology. 15 (8): 937–947. doi:10.1038/ncb2802. ISSN   1476-4679. PMC   3797517 . PMID   23873150.
  14. Pfender, Sybille; Kuznetsov, Vitaliy; Pasternak, Michał; Tischer, Thomas; Santhanam, Balaji; Schuh, Melina (2015). "Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes". Nature. 524 (7564): 239–242. Bibcode:2015Natur.524..239P. doi:10.1038/nature14568. ISSN   1476-4687. PMC   4538867 . PMID   26147080.
  15. Holubcova, Z.; Blayney, M.; Elder, K.; Schuh, M. (5 June 2015). "Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes". Science. 348 (6239): 1143–1147. Bibcode:2015Sci...348.1143H. doi:10.1126/science.aaa9529. ISSN   0036-8075. PMC   4477045 . PMID   26045437.
  16. Zielinska, Agata P.; Holubcova, Zuzana; Blayney, Martyn; Elder, Kay; Schuh, Melina (15 December 2015). "Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect". eLife. 4: e11389. doi: 10.7554/eLife.11389 . ISSN   2050-084X. PMC   4755749 . PMID   26670547.
  17. Zielinska, Agata P.; Bellou, Eirini; Sharma, Ninadini; Frombach, Ann-Sophie; Seres, K. Bianka; Gruhn, Jennifer R.; Blayney, Martyn; Eckel, Heike; Moltrecht, Rüdiger; Elder, Kay; Hoffmann, Eva R.; Schuh, Melina (18 November 2019). "Meiotic Kinetochores Fragment into Multiple Lobes upon Cohesin Loss in Aging Eggs". Current Biology. 29 (22): 3749–3765.e7. doi:10.1016/j.cub.2019.09.006. ISSN   0960-9822. PMC   6868511 . PMID   31679939.
  18. Mogessie, Binyam; Schuh, Melina (2017). "Actin protects mammalian eggs against chromosome segregation errors". Science. 357 (6353): eaal1647. doi: 10.1126/science.aal1647 . hdl: 1983/eeaebe4b-5bda-4cc3-afb5-9576e8a9854d . ISSN   1095-9203. PMID   28839045.
  19. So, Chun; Seres, K. Bianka; Steyer, Anna M.; Mönnich, Eike; Clift, Dean; Pejkovska, Anastasija; Möbius, Wiebke; Schuh, Melina (2019). "A liquid-like spindle domain promotes acentrosomal spindle assembly in mammalian oocytes". Science. 364 (6447). Bibcode:2019Sci...364.9557S. doi:10.1126/science.aat9557. PMC   6629549 . PMID   31249032.
  20. So, Chun; Menelaou, Katerina; Uraji, Julia; Harasimov, Katarina; Steyer, Anna M.; Seres, K. Bianka; Bucevičius, Jonas; Lukinavičius, Gražvydas; Möbius, Wiebke; Sibold, Claus; Tandler-Schneider, Andreas; Eckel, Heike; Moltrecht, Rüdiger; Blayney, Martyn; Elder, Kay (11 February 2022). "Mechanism of spindle pole organization and instability in human oocytes". Science. 375 (6581): eabj3944. doi: 10.1126/science.abj3944 . ISSN   0036-8075. PMID   35143306. S2CID   246750454.
  21. Cheng, S.; Altmeppen, G.; So, C.; Welp, L. M.; Penir, S.; Ruhwedel, T.; Menelaou, K.; Harasimov, K.; Stützer, A.; Blayney, M.; Elder, K.; Möbius, W.; Urlaub, H.; Schuh, M. (2022). "Mechanism of spindle pole organization and instability in human oocytes". Science. 378 (6617): eabq4835. doi:10.1126/science.abq4835. PMID   36264786. S2CID   253045448.
  22. "22 young group leaders recognized as EMBO Young Investigators". Embo.org.
  23. "ERC grantee wins EMBO gold medal". Erc.europa.eu. 16 May 2018.
  24. "Melina Schuh and M. Madan Babu awarded Lister Research Prizes". MRC Laboratory of Molecular Biology. 3 September 2014.
  25. "Past winners of an Early Career Research Award". Biochemistry.org.
  26. "List of winners". Embl.de. 31 May 2023.
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  28. "2019 Winners". Biochemistry.org. Retrieved 8 February 2019.
  29. "DFG, German Research Foundation – Dr. Melina Schuh". www.dfg.de. Retrieved 15 March 2019.
  30. "Melina Schuh". German Academy of Sciences Leopoldina. Retrieved 26 May 2021.
  31. Biology, ©2023 MRC Laboratory of Molecular; Avenue, Francis Crick; Campus, Cambridge Biomedical; CB2 0QH, Cambridge; Uk. 01223 267000. "Women in Science". MRC Laboratory of Molecular Biology. Retrieved 3 May 2023.{{cite web}}: CS1 maint: numeric names: authors list (link)
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