PhD: Embryonic Diapause: pluripotent stem cells placed on hold



At the Institute of Agricultural Science, the Animal Physiology Group addresses the complex
 regulation of physiology. Reproductive challenges are specifically in focus and include an epigenetic perspective on 
cellular communication in livestock and wildlife.

Project background
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 a 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 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 have used the roe deer as model organism to identify key factors involved in the regulation of embryonic diapause. A multi-omics approach has been used to identify transcriptional changes in the embryos and endometrium, while the uterine fluid was used to characterize the proteins, amino acids and acylcarnitines over time. This project specifically focusses on the characterization of molecular patterns and factors that drive developmental pace in the bovine and roe deer.

We hypothesize that diapause related effects are conserved among species, specific pathways can be modified to
 reversibly induce dormancy in bovine stem cells and embryos and artificially diapaused bovine embryos can resume 
development and continue normal development after embryo transfer in vivo.

Job description
The research study funded by the SNF (Swiss National Science Foundation) comprises a comparative approach and
 includes bovine and roe deer as model species, in which we will characterize the molecular patterns during embryo 
development of species with differing developmental pace. We will translate previously described dormancy markers 
established in somatic cells to embryonic stem cells (ESCs) 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 will be applied to reversibly inhibit the identified pathways in bovine stem cells and bovine 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 allows 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.

Your profile
We are looking for an early experienced, highly motivated young researcher with a strong enthusiasm to conduct
 cutting-edge research in the interdisciplinary 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 a related discipline. Profound experience with techniques of molecular 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.

ETH Zurich
ETH Zurich is one of the world’s leading universities specialising in science and technology. We are renowned for our excellent education, cutting-edge fundamental research and direct transfer of new knowledge into society. Over 30,000 people from more than 120 countries find our university to be a place that promotes independent thinking and an environment that inspires excellence. Located in the heart of Europe, yet forging connections all over the world, we work together to develop solutions for the global challenges of today and tomorrow.

We look forward to receiving your online application including a letter of motivation and a detailed CV including copies of certificates. Please address your application to: ETH Zurich, Prof. Susanne E Ulbrich, CH-8092 Zurich. Please note that we exclusively accept applications submitted through our online application portal. Applications via email or postal services will not be considered.

For further information about our groups, please visit our website: For further information about the position and questions related to the research opportunities at ETH Zurich please contact Prof. Ulbrich at (no applications).

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