Meiosis in Mammalian Oocytes

Lead Research Organisation: MRC Laboratory of Molecular Biology

Abstract

All animal life starts with the fertilization of an egg by sperm. During fertilization, the genetic material of the mother and the father are united. Genetic material is stored in the form of chromosomes. The egg contains half of the chromosomes of the mother, and the sperm contains half of the chromosomes of the father.
Sometimes, the embryo may obtain the wrong number of chromosomes. This will most frequently result in pregnancy loss and infertility. In other cases, the embryo may be viable, but it will suffer from congenital disorders such as Down's syndrome, in which the embryo has three instead of two copies of chromosome 21.
From previous work we know that embryos frequently obtain the wrong number of chromosomes, because the egg does not contain exactly half of the chromosomes of the mother. This happens even more frequently, when women get older and is called the “maternal age effect”.
To understand why eggs frequently have the wrong number of chromosomes, we need to investigate how they develop. An egg develops out of a progenitor cell, the oocyte, which still contains the full number of chromosomes. To become a fertilizable egg, the oocyte has to eliminate half of the chromosomes into a small waste cell that is called a polar body. This frequently does not work reliably so that the wrong number of chromosomes stays in the egg. Our aim is to understand, how the chromosomes become prepared for elimination into the polar body, and how the machinery is working that distributes the chromosomes between polar body and egg. This machinery is called the microtubule spindle and consists of protein fibres which separate the chromosomes. If the spindle is abnormal, chromosomes cannot be separated accurately.

Technical Summary

The Schuh laboratory aims to understand meiosis in mammalian oocytes, the progenitor cells of eggs. This topic is of great interest for fundamental research because meiosis is still much more poorly understood than mitosis, especially in mammals. It is also of direct medical relevance because defects in eggs are the leading cause of pregnancy loss and several congenital diseases such as Down’s syndrome.
Our main aim is to understand how defects at the interface between chromosomes and cytoskeletal structures lead to aneuploid eggs and pregnancy loss in mammals. To this end, we study how the meiotic spindle is organized, how it segregates the chromosomes and how the spindle interacts with actin to drive the meiotic divisions. To have a solid foundation for future research, we are developing new tools to study meiosis in mammalian oocytes. For instance, we have been able to carry out the first high content screen for meiotic genes in mammals. We have also been able to establish methods that now allow us for the first time to study the causes of chromosome segregation errors directly in live human oocytes. This opened an exciting new area of research in my laboratory that we plan to expand significantly in the future.
Despite decades of work, we still know relatively little about meiosis in mammalian oocytes. Especially human oocytes have hardly been studied, which is surprising given that all our lives started with the fertilization of an egg. Fertility problems become more and more prominent in our society. Many women in the Western world decide to have a career and postpone childbearing until natural conception becomes difficult or impossible. To improve fertility treatments it is essential that we better understand the mechanisms that govern accurate progression through meiosis and that we analyse the causes of chromosome segregation errors in mammalian oocytes.
 
Description Member of Ethics Committee advising on Home Office project license applications
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in advisory committee
Impact As a member of the local ehtics committee I ensure that animal welfare issues are properly addressed in project license applications.
 
Description EMBO Young Investigator Programme
Amount € 45,000 (EUR)
Organisation European Molecular Biology Organisation 
Sector Learned Society
Country European Union (EU)
Start 02/2013 
End 02/2015
 
Description ERC Starting Grant
Amount € 1,487,611 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 02/2014 
End 02/2019
 
Description FP7 Large Collaborative Grant
Amount € 319,304 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 07/2010 
End 06/2015
 
Description Lister Institute Research Prize
Amount £200,000 (GBP)
Organisation Lister Institute of Preventive Medicine 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2015
 
Title Long term follicle culture for RNAi in mouse oocytes 
Description Adaptation of long term follicle culture methods to deplete stable protein from mouse oocytes 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact RNAi provides an attractive alternative to using conditional knockouts to deplete proteins in mouse oocytes, thus it is a contribution to the 3Rs We just started an RNAi screen to identify new proteins required for homologous chromosome segregation in mammalian oocytes. This should significantly improve our understanding of the causes of infertility, miscarriages and genetic diseases such as Down's syndrome. 
 
Description Collaboration with Marie-France Carlier 
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS)
Country France 
Sector Public 
PI Contribution We tested predictions for the in vitro model of interaction between Fmn2 and Spire proteins in mouse oocytes.
Collaborator Contribution They investigated the interaction between Fmn2 and Spire in vitro.
Impact a manuscript is currently under review
Start Year 2011
 
Description Collaboration with Takashi Hiiragi's lab on mouse embryos 
Organisation European Molecular Biology Laboratory
Department Developmental Biology Unit
Country European Union (EU) 
Sector Public 
PI Contribution We collaborated with Takashi Hiiragi's lab at EMBL Heidelberg on imaging mouse embryos. This collaboration has led to a publication in the Journal of Cell Biology in 2012.
Collaborator Contribution Investigation of spindle assembly in mouse embryos.
Impact Publication in Journal of Cell Biology in 2012 (Courtois et al.)
Start Year 2009
 
Description Development of methods for protein depletion 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Public 
PI Contribution Development of methods for protein depletion
Collaborator Contribution Development of methods for protein depletion
Impact Research not yet published.
Start Year 2014
 
Description MitoSys 
Organisation Austrian Academy of Sciences
Department Institute of Molecular Biotechnology
Country Austria 
Sector Academic/University 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation Curie Institute Paris (Institut Curie)
Country France 
Sector Academic/University 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation Delft University of Technology (TU Delft)
Country Netherlands 
Sector Academic/University 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation European Molecular Biology Laboratory
Department European Molecular Biology Laboratory Heidelberg
Country Germany 
Sector Public 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation Max Planck Society
Department Max Planck Institute for Molecular Cell Biology and Genetics
Country Germany 
Sector Public 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation Research Institute of Molecular Pathology (IMP)
Country Austria 
Sector Academic/University 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation Spanish National Cancer Research Center
Country Spain 
Sector Academic/University 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description MitoSys 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution FP7 Collaborative Grant Task of our group: Investigation of spindle assembly in mouse oocytes and embryos
Collaborator Contribution Exchange of data and techniques
Impact Four recent publications from my lab (Pfender et al. Current Biology 2011; Schuh Nature Cell Biology 2011; Holubcova and Schuh Nature Cell Biology 2013; Clift and Schuh Nat. Rev. Mol. Cell Biol. 2013) were co-funded through this grant. The collaboration is multidisciplinary involving leading European labs working on modelling, biophysical experiments, biochemistry and cell biology.
Start Year 2010
 
Description RNAi Screen and analysis of hits 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Public 
PI Contribution RNAi Screen and analysis of hits
Collaborator Contribution RNAi Screen and analysis of hits
Impact Publication in Nature
Start Year 2014
 
Description Studies of meiosis in human oocytes. 
Organisation Bourn Hall Clinic
Country United Kingdom 
Sector Hospitals 
PI Contribution Studies of meiosis in human oocytes.
Collaborator Contribution Studies of meiosis in human oocytes.
Impact Publications in Science and eLife
Start Year 2012
 
Description Lecture on meiosis for US students 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact 50 pupils attended talk about our research on oocytes and meiosis in general.

class asked for institute visit and several students were interested in applying for PhD programme
Year(s) Of Engagement Activity 2013
 
Description Presentation at meeting of the Senior Infertility Nurse Group UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact The members of the senior infertility nurse group UK were holding their annual meeting in Cambridge, UK. I gave a presentation talking about our research on mouse oocytes. This encouraged questions and discussions afterwards.

Following my presentation, I was also invited by one of the nurses to give a presentation at a conference she was involved in organizing.
Year(s) Of Engagement Activity 2012
 
Description Presentation during George Osborne's visit at the LMB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact explained our research to George Osborne during his visit of the LMB; BBC team was documenting his visit

Many people told me that they saw footage of George Osborne talking to me at his visit of the LMB on TV.
Year(s) Of Engagement Activity 2014
 
Description Presentation during Opening Ceremony of new LMB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact The Queen opened the new LMB building in summer 2013. We gave a short presentation of our work. The Queen also looked at some oocytes on the microscope.

The images and videos of the Queen's visit, including the Queen looking down the microscope at some mouse eggs, were broadcasted worldwide. Thus, this activity has helped to advertise the MRC and work at the LMB.
Year(s) Of Engagement Activity 2013
 
Description Radio interview Cambridge 101 2013 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact an interview about the opening of the new MRC LMB building and the visit of the Queen was broadcasted on Cambridge radio

People in and around Cambridge learnt about opening of new MRC LMB and visit of Queen
Year(s) Of Engagement Activity 2013
 
Description Science Outreach Project Meeting of Minds 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact This project involves encounters between scientists and artists. The encounters are filmed by a film crew. There will a documentary that will screened at an exhibition and might be screened on TV. The artists will create a piece of art that is inspired by the science. There will be also be an exhibition touring several European cities.

The project is still ongoing but has already received strong interest by the media.
Year(s) Of Engagement Activity 2013
 
Description Science outreach project Meeting of Minds TV documentary and art exhibition Lens on Life 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Science outreach project Meeting of Minds TV documentary and art exhibition Lens on Life displayed in varies locations, including Lethaby Gallery, London
Year(s) Of Engagement Activity 2015
 
Description Talk at Bourn Hall IVF Clinic 2013 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact The staff at Bourn Hall IVF Clinic got informed about our research.

The staff at Bourn Hall IVF Clinic felt better informed about our research.
Year(s) Of Engagement Activity 2013
 
Description Talk at MRC LMB Open Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact a wide audience who visited the LMB on its opening day found out about the research in our lab

members of the audience came back to me with positive feedback and questions.
Year(s) Of Engagement Activity 2013
 
Description Talk for Staff at MRC LMB 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Supporters
Results and Impact The MRC LMB's support staff attended a presentation about our work. My presentation encouraged a lively discussion.

Many people working at the LMB told me that they thoroughly enjoyed my presentation and that they found it very useful to gain insights into our research programme, which they are obviously supporting as well. In this way, my presentation helped to motivate the general staff working at the LMB.
Year(s) Of Engagement Activity 2012
 
Description Tea Talk at ARES, Babraham Site 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Supporters
Results and Impact The staff working at the LMB's animal facility, ARES at the Babraham research site was attending a lay talk about our work.

The staff enjoyed my presentation and felt that it was very useful to know more about the research that they are supporting.
Year(s) Of Engagement Activity 2009
 
Description Two lectures within the Zoology Module at Cambridge Univeristy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact I gave two lectures about meiosis within the Zoology Module of the Natural Sciences Tripos at Cambridge University. I gave supervisions and marked essays.

Lecturers in this course were all groupleaders from leading research institutes in Cambridge. My lectures were amongst the best ones within the course, based on scores given by the students. Very many students decided to write an essay about the question that I suggested for their exams. I even received an email from a student, saying how much they had enjoyed the lectures and a request from another student who wanted to undertake an internship in my lab because they enjoyed the lectures so much.
Year(s) Of Engagement Activity 2012