Modelling brain development with microglia-containing three-dimensional cerebellar organoids

This research will develop novel methodologies to i) generate the first human iPSC-derived microglia containing cerebellar organoids to more accurately model aspects of human cerebellar development in vitro, ii) better understand the role of microglia during cerebellar development, and iii) to advance UK-based drug discovery. Our study will have an immediate impact on the academic community, who will benefit from access to our novel methods and their application in wider contexts.

We hope that our newly developed methods will replace some of the currently used in vivo mammalian models for cerebellar research, and thus have an impact on the number of animals used for research, contributing to the 3Rs.

Further impact will be achieved by engaging the student in public engagement and outreach events that will highlight the relevance of this research and further its public understanding.

The DPhil student will benefit from training in cutting-edge technology and the immersion in both an academic and industrial environment, which will greatly enhance their future career prospects. The developed hiPSC models will provide a unique platform for future preclinical drug discovery, optimisation,

and testing. By partnering with IIUK, the research will have direct impact on UK-based industrial R&D activities. IIUK is based in Cambridge, UK and is an early-stage R&D centre for Insmed Inc., identifying and validating new targets with relevance in many disease areas for this global pharmaceutical company.

In the future, cerebellar models derived from patient iPSCs are poised to provide important insight into disease-causing mechanisms and have enormous potential for the development of personalized medicine. Thus, in the long term our research will impact on patients as well as the pharmaceutical sector in the UK and worldwide, enhancing quality of life and society's health and wellbeing.