Innovative approaches to embryo implantation research in health and disease
IMPLANTEU is dedicated to pioneering research in the field of embryo implantation in health and disease. This international network is committed to developing a molecular blueprint of implantation, especially in human and cattle. This will advance knowledge and research tools in the field of human implantation and will enhance implantation fitness for agricultural productivity. The project leverages cross-disciplinary expertise spanning reproductive and stem cell biology, medicine, physiology, ethics, law, and advanced technologies such as stem cell-based embryo models, organoids, machine learning, and organs-on-chip. This program is designed to cultivate the next generation of researchers, equipping them with the necessary skills to contribute significantly to the field of reproductive success and embryo implantation research.
We are excited to announce 13 doctoral early stage researcher (ESR) positions, available from October 2024, geared towards candidates passionate about the implications of embryo implantation in human health and agriculture. Selected candidates will engage in multidisciplinary research, participate in international secondments across academic and industrial settings, and contribute to high-impact publications and conferences.
ESR projects:
- ESR1: Impact of chromosomal mosaicism on human peri-implantation in vitro (Host: Eugin Group, Barcelona, Spain, Supervisor: Dr. Mina Popovic)
- ESR2: Understanding molecular mechanisms underlying Recurrent Implantation Failure (RIF) (Host: Eugin Group, Barcelona, Spain, Supervisor: Dr. Irene Miguel-Escalada)
- ESR3: Invasive properties of trophoblast subtypes during implantation (Host: Medical University of Graz, Graz, Austria, Supervisor: Prof. Martin Gauster)
- ESR4: Trophoblastic anticoagulant proteins at the implantation front (Host: Medical University of Graz, Graz, Austria, Supervisor: Prof. Martin Gauster)
- ESR5: Ethical aspects in embryo research developments (Host: KU Leuven, Leuven, Belgium, Supervisor: Prof. Pascal Borry)
- ESR6: Human endometrium-on-chip design and development (Host: BiomimX SRL, Milan, Italy, Supervisor: Dr. Paola Occhetta)
- ESR7: Effects of Progesterone in endometrium during euploid blastocyst transfer (Host: Ghent University, Ghent ,Belgium, Supervisor: Prof. Dominic Stoop)
- ESR8: Optimizing 3D human endometrium models for early pregnancy (Host: Leiden University Medical Centre, Leiden, The Netherlands, Supervisor: Prof. Susana M. Chuva de Sousa Lopes)
- ESR9: Role of embryonic TLR-mediated innate immune system during preimplantation (Host: University of Milan, Milan, Italy, Supervisor: Prof. Alberto M. Luciano)
- ESR10: Machine learning for endometrial receptivity (Host: Valencia Polytechnic University, Valencia, Spain, Supervisor: Prof. Valery Naranjo Ornedo)
- ESR11: Investigating IVF embryo loss in cattle (Host: University College Dublin, Dublin, Ireland, Supervisor: Prof. Patrick Lonergan)
- ESR12: Trained immunity in endometrial cells (Host: University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Supervisor: Prof. Petra Arck)
- ESR13: Drug screening platform combining blastoids and endometrial cells (Host: Institute of Molecular Biotechnology, Vienna, Austria, Supervisor: Dr. Nicolas Rivron)
Application Criteria:
- Applicants must not have resided or carried out their main activity (work, studies, etc.) in the country of the host institution for more than 12 months in the 3 years immediately before the recruitment date.
- Applicants should be in the first four years (full-time equivalent research experience) of their research careers and have not been awarded a doctoral degree.
Application process: Candidates are invited to apply by submitting a detailed CV and motivation letter, specifying the ESR position of interest (ESR1-ESR13). Please send your applications to implanteu@eugin.es or directly contact the host institutions for more details.
Here are the details for the two PhD positions (ESR3 and ESR4) at the Medical University of Graz, Austria:
ESR3
Project Title: Invasive properties of trophoblast subtypes during implantation
Background:
Successful human pregnancy strongly depends on crucial mechanisms, including pre-implantation development of the embryo and its implantation into the uterine wall [1]. Following embryo implantation, the placenta develops, a short-lived organ with a remarkable array of functions at the maternal-fetal interface. It substitutes for fetal organs in early pregnancy and ensures adequate embryonic/fetal growth by transferring nutrients and gases between the mother and the embryo/fetus. [2]. A key placental cell type involved in all these processes is the trophoblast. It originates from the blastocyst and differentiates into either polar cells, serving typical epithelial functions, or into apolar invasive cells that remodel and adapt the maternal endometrial vessels and glands to progressing pregnancy [3,4].
Hypothesis and Objectives:
So far, the knowledge on the behavior of first trophoblast lineages (mononuclear as well as multinucleated / syncytial) is mostly based on animal studies or few images from archival human specimens. Hence, this project aims to elucidate mechanisms of trophoblast-driven blastocyst penetration through the uterine epithelium.
Methodology:
Human trophoblast stem cell (hTSC)-derived organoids will be co-cultured in a hypoxic workstation with endometrial explants from IVF patients or women undergoing elective termination of pregnancy. Co-cultured tissues will be subjected to histological surveys using lightsheet and confocal microscopy to study attachment on and penetration through the endometrial epithelium. Moreover, molecular analyses, including single cell RNA sequencing, in situ hybridization, qPCR and immunoblotting will be applied.
References:
[1] M. Gauster, G. Moser, S. Wernitznig, N. Kupper, B. Huppertz, Early human trophoblast development: from morphology to function, Cell. Mol. Life Sci. CMLS 79 (2022) 345. https://doi.org/10.1007/s00018-022-04377-0.
[2] G. Desoye, M. Gauster, C. Wadsack, Placental transport in pregnancy pathologies, Am. J. Clin. Nutr. 94 (2011) 1896S-1902S. https://doi.org/10.3945/ajcn.110.000851 [doi].
[3] B. Huppertz, V.M. Berghold, R. Kawaguchi, M. Gauster, A variety of opportunities for immune interactions during trophoblast development and invasion, Am. J. Reprod. Immunol. N. Y. N 1989 67 (2012) 349–357.
[4] G. Moser, G. Weiss, M. Gauster, M. Sundl, B. Huppertz, Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro, Hum. Reprod. Oxf. Engl. 30 (2015) 2747–2757. https://doi.org/10.1093/humrep/dev266 [doi].
ESR4
Project Title: Trophoblastic anticoagulant proteins at the implantation front
Background:
Human placentation depends on sufficient invasion of trophoblasts into endometrial blood vessels, allowing their remodeling to provide adequate maternal blood perfusion of the placenta and supply of oxygen and nutrients to the developing embryo/fetus [1]. Erosion and opening of these vessels by invading trophoblasts requires a well-balanced hemostatic system. In particular, anticoagulant factors must be tightly controlled with respect to the timing and location of their expression at the embryo implantation site [2]. Trophoblast insufficiency and coagulation abnormalities have been linked to early pregnancy loss [3]. However, a detailed characterization of the human trophoblastic anticoagulant machinery during the very early stages of placentation does not yet exist.
Hypothesis and Objectives:
The overarching aim of this project is to establish a spatio-temporal map of the trophoblastic anticoagulant machinery in the very early stages of pregnancy. Expression of anticoagulant factors will be analyzed in different trophoblast subpopulations. Moreover, the hypothesis will be tested whether trophoblastic anticoagulant factors are dysregulated in recurrent miscarriage cases.
Methodology:
Early human trophoblast-invaded endometrial samples will be subjected to snRNA sequencing and spatial transcriptomics. Obtained data sets will be validated by in situ hybridization, qPCR, immunoblotting and immunostaining on recurrent miscarriage samples and healthy gestational age-matched controls. Finally, anticoagulant factors will be analyzed in trophoblast stem cell (hTSC)-derived organoids after co-cultures with endometrial explants.
References:
[1] M. Gauster, G. Moser, S. Wernitznig, N. Kupper, B. Huppertz, Early human trophoblast development: from morphology to function, Cell. Mol. Life Sci. CMLS 79 (2022) 345. https://doi.org/10.1007/s00018-022-04377-0.
[2] D. Forstner, J. Guettler, M. Gauster, Changes in Maternal Platelet Physiology during Gestation and Their Interaction with Trophoblasts, Int. J. Mol. Sci. 22 (2021) 10.3390/ijms221910732. https://doi.org/10732 [pii].
[3] J. Kwak-Kim, K.M. Yang, A. Gilman-Sachs, Recurrent pregnancy loss: a disease of inflammation and coagulation, J. Obstet. Gynaecol. Res. 35 (2009) 609–622. https://doi.org/10.1111/j.1447-0756.2009.01079.x.
Link to the EURAXESS website: https://euraxess.ec.europa.eu/jobs/270249
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20 Sep 2024