PhD position: Embryonic Diapause - pluripotent stem cells placed on hold in Zürich

100%, Zurich, fixed-term

The Animal Physiology Group addresses the complex regulation of reproductive physiology. Challenges include the disentangling of maternal-embryonic interactions and cellular communication prior to implantation in livestock and wildlife.

Embryonic diapause is a peculiar phenomenon, in which the pace of embryonic preimplantation development is temporarily halted or reduced. It highlights a striking similarity to cellular dormancy as quiescent state of non-proliferating cells reacting to a specific environmental condition. Knowledge about the molecular mechanisms involved in regulating embryonic diapause is promising for use during in vitro embryo production as an alternative for cryopreservation, but also for studying cell proliferation inhibition to extend pluripotency, to arrest senescence and to suppress cancer proliferation. Remarkably limited knowledge is available to date. We use the roe deer as an animal model to identify key factors involved in the regulation of embryonic diapause. A multi-omics approach has allowed to identify transcriptional changes in the embryos and the endometrium, while the uterine fluid was used to characterize the proteins, amino acids and acylcarnitines over time. The project aims at finding molecular patterns and identifying key factors that are associated with and drive embryonic developmental pace. If diapause related effects are conserved among species, we hypothesize that specific pathways can be reversibly inhibited to induce dormancy in bovine stem cells and that artifically induced diapausing bovine embryos can be transfered for resumed development in vivo.

This doctoral research study funded by the SNF (Swiss National Science Foundation) comprises a comparative approach and includes bovine and roe deer as model species. We will characterize the molecular patterns during embryo development, translate previously described dormancy markers established in somatic cells to embryonic stem cells as a screening system, and elucidate the impact of dormancy inducing factors on cell cycle progression. We will then introduce CRISPRi in ESCs to screen for novel dormancy inducing factors. Novel chemical inhibitors targeting the discovered factors are applied to reversibly inhibit the identified pathways in bovine stem cells and embryos produced in vitro. Next-generation transcriptome and methylome sequencing will critically assess the developmental competence of the embryos after reversible developmental arrest. Identifying molecular markers of cellular dormancy will allow the development of culture conditions under which embryos may be kept in a reversible diapause-like stage. It may additionally provide implications for further livestock and endangered wildlife species, as well as the field of stem cell research and human medicine.

We offer a very well-equipped facility at ETH Zurich in a working environment of a young, emerging research group. The successful candidate will have access to state-of-the-art molecular laboratories at ETH and UZH, specifically sequencing and high-performance computing facilities. Publication activities and participations at international conferences are promoted.

We are looking for an early experienced, highly motivated young researcher with a strong enthusiasm to conduct cutting-edge research in the field of functional genomics in the context of wildlife physiology and stem cell research. Applicants have completed a master degree in biochemistry, biology, molecular biotechnology, agricultural sciences or related disciplines. Profound experience with techniques of molecular and/or cell biology is required. Candidates have the ability to work independently in an interdisciplinary research environment. Very good knowledge of spoken and written English is essential.

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