Research Programmes
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Mammalian Reproduction
MVDr. Martin Anger, Ph.D.
Research Group Leader
THEMATIC RESEARCH FOCUS
RESEARCH AREAS
- Acquisition of meiotic competence in mammalian oocytes
- Regulation of chromosome segregation in mammalian meiosis
- Effect of maternal aging on chromosome segregation errors in oocytes
- Fertilisation and transition from meiosis into mitosis
- Regulation of chromosome segregation during early embryonic development
MAIN OBJECTIVES
- To identify the essential factors important for acquisition of meiotic competence in mammalian oocytes, especially those that are conserved between species.
- To obtain detailed description of the crucial molecular mechanisms controlling chromosome segregation in mammalian oocytes.
- To determine which of those mechanisms are primarily affected by maternal aging in mammalian oocytes.
- To study the transition from meiosis into mitosis during fertilisation and accompanying changes of the cell cycle regulatory mechanisms.
- To study the regulation of chromosome segregation during early embryonic development in mammals, especially the role of checkpoint mechanisms in this process.
CONTENT OF RESEARCH
Animal models of mammalian reproduction
Mammalian oocytes are unique cells that first appear during early embryonic development. After the initial stages of the meiotic program, which also involves recombination and exchange of genetic material, oocytes are arrested at the prophase of the first meiotic division until hormonal stimulation triggers resumption of meiosis. This extremely long interruption of the meiotic program that in some species, such as humans, might last for decades can cause cell cycle disorders during later stages of the meiosis. Manifested by insufficient competence to complete meiosis or failure of chromosome segregation leading to aneuploidy, these errors accumulate with age and present serious problems for human reproduction such as increased levels of abortion or developmental disorders.
Research group will focus on two essential events in mammalian oocytes. We will study how the oocytes acquire competence to resume meiosis during growth and how the segregation of chromosomes during the resumption of meiosis is controlled. In particular we are interested in changes introduced into those events by maternal aging. Using mouse oocytes together with oocytes isolated from farm animals, we will be able to take advantage of the mouse knockout and transgenic lines and close to human meiotic progression observed in farm animals. Using techniques such as live cell confocal microscopy and kinase assays based on FRET biosensors, we will be able to study individual cells. Our results will be important for human reproduction, as well as for the improvement of techniques used in the reproduction of farm animals.
In order to obtain a complete picture about regulation of chromosome segregation at the onset of development, apart from studying this process in oocytes we will also focus our attention to the fertilisation and early embryonic development. This part of the mammalian development represents and important transition between meiotic cell cycle and mitosis and for our better understanding of the mechanisms regulating cell division and chromosome segregation and also errors, which might occur in this process, this stage of development is essential. Since the chromosome segregation during early embryonic development in human is highly error prone, our results will be valuable for preventing such errors.
Updating research infrastructure by introducing new state-of-the-art techniques to our laboratory is also one of our goals. To achieve this, we would like to introduce live imaging of oocytes and embryos in combination with kinase assays in single cell. These new techniques will not only substantially increase our chance to compete in the field for the future, but the methods and approaches developed during our study will also potentially have robust impact on reproduction medicine and animal biotechnology.
KEY RESEARCH EQUIPMENT
PLANNED RESEARCH INFRASTRUCTURE
Technology Units
Analysis of mammalian gametes and embryos using live microscopy
CURRENT RESEARCH INFRASTRUCTURE
Our current research infrastructure includes basic equipment for in vitro culture and analysis of oocytes and embryos and basic equipment for molecular biology techniques such as RT PCR, in vitro transcription of mRNA, electrophoresis, gel documentation etc. We have also available facility for housing laboratory animals including transgenic mouse facility and facility for housing large farm animals.
MAIN PROJECTS
- Marie Curie Reintegration Grant, 2009-2011, M. Anger, Institute of Animal Physiology and Genetics, AS CR.
- Regulation of chromosome segregation during meiosis (IAA501620801), Academy of Sciences of the Czech Republic, 2008-2010, M. Anger, Veterinary Research Institute, A. Hampl, Masaryk University.
- EMBO Installation Grant, 2009-2011, M. Anger, Institute of Animal Physiology and Genetics, AS CR.
- The changes in important regulatory mechanisms of meiotically dividing mammalian oocytes induced by ageing (GA523/09/0743), Czech Science Foundation, 2009-2012, M. Anger, Institute of Animal Physiology and Genetics AS CR, M. Ješeta, Veterinary Research Institute.
SELECTED PUBLICATIONS
- HORNAK, M., JESETA, M., MUSILOVA, P., PAVLOK, A., KUBELKA, M., MOTLIK, J., RUBES, J., ANGER, M. Frequency of aneuploidy related to age in porcine oocytes. PLoS One. 2011, 6(4), p. e18892.
- XU, Z., CETIN, B., ANGER, M., CHO, U., S., HELMHART, W., NASMYTH, K., XU, W. Structure and function of the PP2A-shugoshin interaction. Molecular Cell. 2009, 35(4), p. 426-441.
- MCGUINNESS, B., E., ANGER, M., KOUZNETSOVA, A., GIL-BERNABE, A., M., HELMHART, W., KUDO, N., R., WUENSCHE, A., TAYLOR, S., HOOG, C., NOVAK, B., NASMYTH, K. Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint. Current Biology. 2009, 19(5), p. 369-380.
- TAM, O., H., ARAVIN, A., A., STEIN, P., GIRARD, A., MURCHISON, E., P., CHELOUFI, S., HODGES, E., ANEGER, M., SACHIDANANDAM, R., SCHULTZ, R., M., HANNON, G., J. Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes. Nature. 2008, 453(7194), p. 534-538.
- 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. Resolution of chiasmata in oocytes requires separase mediated proteolysis. Cell. 2006, 126(1), p. 135-146.
EUROPEAN UNION
