Development of vascularisation tools for iPSC-derived organoids
About the role
Development of vascularisation tools for iPSC-derived organoids
In the Crick's Stem Cells and Organoids Platform.
Key information
This sandwich placement will be based in the Stem Cells and Organoids Platform (SCOP) STP supervised by Sara Tamagno.
Project summary
The stem cells and organoids field is rapidly evolving, with broad-ranging applications in developmental biology, disease modelling, tissue engineering, and cell therapies. Induced pluripotent stem cell (iPSC)-derived organoids offer a valuable and versatile tool to study complex biological processes such as human embryonic development, and can recapitulate key features of adult tissue physiology in health and disease. However, current models have limited cellular complexity, rely on prolonged differentiation protocols, and often lack mature functional traits. A strategy to overcome physiological limitations is organoid vascularisation. This can be achieved by differentiating the same iPSC into [1] tissue-specific organoids and [2] an organotypic vasculature comprising endothelial cells and surrounding stromal cells. Upon co-culture, this strategy has the potential to promote nutrient exchange and paracrine signalling for improved differentiation, patterning and morphogenesis.
The project will focus on establishing tools and methodologies to develop vascularised human in vitro models, using human pluripotent stem cells. The project will include one or more of the following aims: 1) development of protocols for the derivation of iPSC-derived endothelial and perivascular cells; 2) optimisation of embedding strategies for iPSC-derived vasculature into vascular chip systems; 3) co-culture of iPSC-derived vasculature and organoids; 4) functional assessment/validation of co-culture systems. The results of this project will contribute towards the development of a versatile organ-on-a-chip vascularisation tool applicable to multiple iPSC-derived organoid models.
As part of the project, the student will learn several cell and molecular biology techniques, including aseptic technique, 2D and 3D cell culture, immunofluorescence (IF), imaging, flow cytometry, RNA extraction, PCR, and data analysis.
Candidate background
The post holder should embody and demonstrate the Crick ethos and ways of working: bold, open and collegial. The candidate must be registered at a UK Higher Education Institution, studying in the UK and must have completed a minimum of two years’ undergraduate study in a relevant discipline, and on track to receive a final degree grade of 2:1 or 1. In addition, they should be able demonstrate the following experience and key competencies:
- This project would suit a candidate studying biomedical sciences, biotechnology, biology or related discipline.
- Good knowledge in relevant scientific area(s)
- Good written and spoken communication skills
- Ability to work independently and also capable of interacting within a group
References
- Heinzelmann, E., Piraino, F., Costa, M., Roch, A., Norkin, M., Garnier, V., . . . Brandenberg, N. (2024) iPSC-derived and Patient-Derived Organoids: Applications and challenges in scalability and reproducibility as pre-clinical models.Current Research in Toxicology7: 100197.PubMed abstract
- Salmon, I., Grebenyuk, S., Abdel Fattah, A.R., Rustandi, G., Pilkington, T., Verfaillie, C. and Ranga, A. (2022) Engineering neurovascular organoids with 3D printed microfluidic chips.Lab on a Chip22: 1615–1629.PubMed abstract