Dr Anthony Perry
Our research combines molecular and embryological techniques to understand the egg-to-embryo transition in a mouse model: how is it that two cells destined to die (sperm and egg) combine during fertilisation so that they not only do not die, but within a few hours form a cell that gives rise to an entire individual? If this problem may be likened to a 2000-piece jigsaw puzzle, science has so far only completed some of the edges; there's a big hole in the middle. This is because fertilisation uniquely integrates so many intricate processes in a single cell. It triggers a transition from meiotic to mitotic cell cycles involving a unique cytostatic factor, Emi2, which we identified (EMBO J.) and showed to require Zn2+ for its activity (Development).
We have shown links between the cell cycle and chromatin remodeling (Dev Biol) and are trying to find out more. We find parallels between the egg-to-embryo transition and cancer (Development) and are increasingly lead to explore the relationship between fertilisation, the induction of pluripotency and carcinogenesis. We have established and developed techniques and molecular reagents with which to manipulate developmentally critical events during and following fertilisation.
We are the only laboratory in the UK successfully using piezo-actuated micromanipulation, which is essential for the manipulation of delicate mouse eggs. All nuclear transfer cloned mice have been made using piezo; we recently produced England's first cloned mouse. We can monitor the outcome of piezo-actuated micromanipulation by fluorescence imaging, biochemical analyses and developmental profiling. Our approach allows us to harness the biology of fertilisation for new technologies, such as a method of transgenesis developed by us (Science). The egg-to-embryo transition during natural fertilisation is ~100% efficient, so understanding how it works will prove essential for the development of safe strategies in regenerative medicine.
Suzuki, T., Asami, M., Hoffmann, M., Lu, X., Gužvić, M., Klein, C. A. and Perry, A. C. F., 2016. Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes. Nature Communications, 7, 12676.
Okamoto, Y., Yoshida, N., Suzuki, T., Shimozawa, N., Asami, M., Matsuda, T., Kojima, N., Perry, A. C. F. and Takada, T., 2016. DNA methylation dynamics in mouse preimplantation embryos revealed by mass spectrometry. Scientific Reports, 6, 19134.
Bosley, K., Botchan, M., Bredenoord, A., Carroll, D., Charo, R. A., Charpentier, E., Cohen, R., Corn, J., Doudna, J., Feng, G., Greely, H., Isasi, R., Ji, W., Kim, J.-S., Knoppers, B., Lanphier, E., Li, J., Lovell-Badge, R., Martin, G. S., Moreno, J., Naldini, L., Pera, M., Perry, A., Venter, J. C., Zhang, F. and Zhou, Q., 2015. CRISPR germline engineering-the community speaks. Nature Biotechnology, 33 (5), pp. 478-486.
Suzuki, T., Asami, M. and Perry, A. C. F., 2014. Asymmetric parental genome engineering by Cas9 during mouse meiotic exit. Scientific Reports, 4, p. 7621.
Suzuki, S., Iwamoto, M., Saito, Y., Fuchimoto, D., Sembon, S., Suzuki, M., Mikawa, S., Hashimoto, M., Aoki, Y., Najima, Y., Takagi, S., Suzuki, N., Suzuki, E., Kubo, M., Mimuro, J., Kashiwakura, Y., Madoiwa, S., Sakata, Y., Perry, A. C. F., Ishikawa, F. and Onishi, A., 2012. Il2rg gene-targeted severe combined immunodeficiency pigs. Cell Stem Cell, 10 (6), pp. 753-758.
Onishi, A. and Perry, T., 2012. Practical Manual of In Vitro Fertilization:Livestock production via micromanipulation. In: Practical Manual of In Vitro Fertilization.Vol. 41. 7 ed. Springer, p. 371.
VerMilyea, M. D., Maneck, M., Yoshida, N., Blochberger, I., Suzuki, E., Suzuki, T., Spang, R., Klein, C. A. and Perry, A. C. F., 2011. Transcriptome asymmetry within mouse zygotes but not between early embryonic sister blastomeres. EMBO Journal, 30 (9), pp. 1841-1851.
Suzuki, T., Suzuki, E., Yoshida, N., Kubo, A., Li, H., Okuda, E., Amanai, M. and Perry, A. C. F., 2010. Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase. Development, 137 (19), pp. 3281-3291.
Suzuki, T., Yoshida, N., Suzuki, E., Okuda, E. and Perry, A. C. F., 2010. Full-term mouse development by abolishing Zn2+-dependent metaphase II arrest without Ca2+ release. Development, 137 (16), pp. 2659-2669.