PhD studentship: Engineering an in vitro human embryo implantation platform to study pathologies arising in early pregnancy

A fully funded PhD opportunity to participate in the world-leading research undertaken by the EPSRC Doctoral Landscape Award at the University of Sheffield.

Embryo implantation is the step in early pregnancy where the founding tissue of the placenta from the embryo, called the trophoblast, establishes a physical connection with the mother at the inner lining of the uterus, called the endometrium. It is estimated that 75% of pregnancy losses occur during the implantation process. This critical step of early pregnancy, often referred to as a “black box”, has remained poorly understood due to its inaccessibility. However, study of this period is now possible in vitro due to advancements in stem cell-based models of the embryo, blastoids (Yanagida et al. 2021, PMID: 33957081 ), and the endometrium, endometrial assembloids (Rawlings et al. 2021, PMID: 34487490).

The main aim of this PhD project is to establish a human implantation platform that integrates blastoids and endometrial assembloids to study aspects of the embryo and endometrium that impact the implantation process. We have recently generated new pluripotent stem cell lines from single cells of embryos which allow us to study the impact of genetic variation in development (Strawbridge et al. 2022, PMID: 34870826). Concurrently, we have developed a base model of the endometrium that captures features of uterine physiology (Rawlings et al. 2024, PMID: 37402095). This interdisciplinary project will combine these tools with methods from stem cell biology, embryology, materials science, advanced imaging, and data science to:

1. Investigate the effects of aneuploidies on human embryonic development potential through blastoid generation.

2. Engineer an advanced endometrial assembloid that mimics the natural environment of the uterus.

3. Assess the impact of genetic variation in the embryo on implantation using a blastoid-endometrial assembloid co-culture system.

Outcomes of this work will be benchmarked against the Carnegie Collection of Embryology (https://www.ehd.org/virtual-human-embryo) and the Boyd Collection (https://www.trophoblast.cam.ac.uk/Resources/boyd-collection).

This highly interdisciplinary project will involve collaboration between four complementary research groups, providing the student with a highly desirable skill set spanning health, science, and engineering. Expertise will be drawn from reproductive physiology (Emma Lucas), developmental biology (Stanley Strawbridge), stem cell biology (Ivana Barbaric), and materials science (Frederik Claeyssens). The student will benefit from interactions with the vibrant community of reproductive physiologists, stem cell biologists, and materials scientists.

This project represents an exciting opportunity to establish a launching pad to advance our understanding of a critical stage in human reproduction which has the potential to identify pathologies and prescribe interventions, ultimately contributing to better reproductive health outcomes.

The University of Sheffield is one of the leading Russell Group universities in the UK. We carry out cutting-edge research with strong links to industry. When you enrol to do a PhD with us, you will be working with world-leading academics and have access to top of the range facilities. As a PhD student you will have the opportunity to gain skills not only to conduct research, but also to take your career to the next level, whether you want to stay in academia, go into industry or the public sector, or set up your own company. You will have access to a range of training and support services to help you excel in your studies and beyond.

How to apply

Interested candidates are strongly encouraged to contact the project supervisors to discuss your interest in and suitability for the project prior to submitting your application.

Please refer to the EPSRC DLA webpage for detailed information about the EPSRC DLA and how to apply.