About the Project
Although extremely promising, organoid technologies are still in their infancy and some challenges need to be overcome before they can be widely implemented. In particular, organoid-based assays lack high-throughput screening capabilities: 3D fluorescence imaging allow the study of various processes mimicked in organoid platforms, but achieving high-throughput imaging with high spatial resolution is essential for their use as disease modelling platforms. In the case of host-microbe interaction studies, simplifying the analysis of the complex interplay between organoid cells and colonising microorganisms will greatly contribute to the establishment of these technologies as transformative research tools.
Recent advances in genome-editing tools, such as the CRISPR/Cas9 technology, have allowed the development of organoids for gene therapy. Stem cells from which organoids are derived can be modified, and the resulting organoids used to generate healthy tissues. These modified organoids have opened new possibilities for the development of ‘synthetic’ organoids. In a same way, stem cells can be engineered with synthetic gene circuits that endow derived organoids with customisable functions. This synthetic biology approach allows to program organoids with new behaviours and in particular with new reporting capabilities that can facilitate the microscopic analysis of a wide variety of organoid-based investigations (host-pathogen interaction, drug screening, etc.).
This project aims at designing ‘intelligent’ organoids that can spatially report on their interaction with microbes. As a proof-of-concept, ES cells will be programmed with synthetic gene circuits that allow reporter expression upon bacterial interaction. These engineered cells will be used to derive intestinal organoids and their 3D spatiotemporal imaging optimised. The cellular interactions between bacteria and organoid cells will be investigated to answer various questions relating to pathogen gut infection and the effect of drug treatment on different bacterial populations. Within this project, the student will receive training in scientific research skills and analytical methods (such as microscopy and flow cytometry), but also acquire specific skills in molecular and synthetic biology, as well as stem cells and organoid biology.
The School of Biological Sciences is committed to Equality & Diversity: https://www.ed.ac.uk/biology/equality-and-diversity
How to Apply:
The “Institution Website” button will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process.
Based on your current searches we recommend the following search filters.
Based on your current search criteria we thought you might be interested in these.