The University of Nottingham in the UK invites applications for a PhD Studentship on Stem Cell Biology and Disease Modelling in the 2022/23 academic session.
This project will develop an in vitro model of early embryogenesis by combining two novel technologies and then work with key figures in the developmental biology community to share the new methodology. In addition, recognising the Replacement, Refinement and Reduction of Animals in Research (3Rs) ‘valley of death’ that limits widespread uptake of 3Rs relevant technologies, the student will also undertake a placement with a highly regarded peptide manufacturer, to learn how to manufacture, test and market products such as the hydrogels effectively.
Developed and optimised by Dr David Turner during his NC3Rs fellowship, gastruloids are aggregates of mouse embryonic stem cells which activate gene networks and undergo patterning events similar to that seen in a six to ten-day-old embryo. Gastruloids have been demonstrated to provide a replacement technique for genetically modified (GM) mouse embryos in the study of embryogenesis. The stem cells can be directly manipulated, removing the need for breeding GM mouse lines in addition to avoiding the need to kill pregnant mice for embryo collection. However, studying later developmental events such as somitogenesis requires additional support derived from interactions with the extracellular matrix. Currently, that matrix is usually provided by Matrigel, a commercial preparation from mouse tumour extract, with significant batch-to-batch variation and complexity that makes it difficult to unpick complex biological questions. Matrigel can mask disease-specific cell-matrix interactions which are of significance in modelling disorders where these are an important part of the disease pathology and resistance to therapy.
To solve the Matrigel problem, the Merry lab have developed synthetic peptide hydrogels (SPH). We have used them to create in vitro models of breast cancer and demonstrated they support 3D culture for multiple other cell types, including embryonic stem cells. The SPH technology is reproducible and adaptable and has been successfully shared with other groups. The SPH provide a ‘blank slate’ with which to test the role of matrix proteins and glycans as well as to evaluate the role of matrix stiffness. To investigate that aspect further, we’ve also teamed up with an expert in optics, Dr Amanda Wright, with whom we have developed a new microscope that allows us to understand how cell clusters interact with their local matrix at the cellular level. The high levels of reproducibility possible using the gastruloid and SPH technologies will enable us to build a detailed map of the local mechanical forces that impact on early developmental decisions and will showcase the new model system to encourage uptake.
Training will be provided in cross-discipline cutting-edge techniques including the growth and characterisation of gastruloids, in vitro models of development in synthetic 3D hydrogels, light-sheet imaging and microrheology. As well as training in the importance of the 3Rs, the student will also have the opportunity to collaborate with the group of Dr Jesse Veenvliet, a group leader at the Max Plank Institute of Molecular Cell Biology and Genetics in Dresden, Gemany and will also develop entrepreneurial skills will input from a local commercial partner.
Worth of Award
- This is a 4 -year studentship fully funded for UK candidates by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
- International candidates are eligible to apply, however they would need to fund the difference in tuition fee.
- A high 2.1 or 1st class degree in a relevant biological degree.
- This exciting project requires a motivated and inspired candidate with a forward thinking, positive, can-do attitude and a strong interest in the 3Rs principles.
How to Apply
- Candidates should complete an online application.
- Please email a CV along with a covering letter stating why you are interested in the project and how your attributes and skills align with the project goals to [email protected] You are guided to complete this step as soon as possible.
Deadline: The position will be filled when suitable candidates have been identified. Early application is strongly encouraged, by March 31, 2022