Project No. 2427

STANDARD PROJECT

Primary Supervisor

Dr Sassan Hafizi – University of Portsmouth

Co-Supervisor(s)

Dr Sandrine Willaime-Morawek – University of Southampton

Summary

Microglia are the principal immune cells of the brain and play important roles in neuronal development and homeostatic functions.

Microglia are the principal immune cells of the brain and play important roles in neuronal development and homeostatic functions. Also, as key regulators of neuroinflammation, microglia also feature greatly in the progression of neurodegenerative diseases such as Alzheimer’s disease. The majority of studies on this highly specialised brain cell type have been conducted using rodent cells, and mainly in 2D cell culture models. Although much information has been gained from these models, they are limited in lacking a 3D environment, and one that includes multiple cell types and of human origin. Therefore, there is a need for in vitro models that recapitulate better the true conditions within the human brain, which would enable neuroinflammation researchers to gain valuable new insights into the role of CNS microglia in both health and disease. The advent of novel cell culture models derived from human induced pluripotent stem cells (iPSCs) represents a major leap in cell biology research

and promises to deliver much needed information to complement as well as supersede that already gained from animal-based models. Recently, a few protocols have been reported for differentiation of microglia from human iPSCs. These enable one to generate large numbers of highly pure human microglia in culture. Whilst the Hafizi lab has expertise in microglial research and cell culture methods, the Willaime-Morawek lab has developed a novel human iPSC-derived 3D neural culture model consisting of a mix of astrocytes and mature neurons. The aim of the PhD project is to bring this expertise together to develop a further refined human 3D CNS cell culture model that additionally contains microglia. This will represent the most relevant in vitro human culture model yet, to enable study of the biology of CNS cells under specific experimental conditions, improving reliability, reproducibility and concomitantly reducing the need for dependence on animals.