Interplay between cholesterol homeostasis and neural development

The brain is the most cholesterol rich organ in the body. Cholesterol is an essential structural molecule in cell
membranes, a major component of myelin sheaths and is important for synapse formation. Inborn errors of
cholesterol biosynthesis lead to neurodevelopmental defects, in addition altered cholesterol homeostasis has been
linked to neurodevelopment disorders, including autism. Mounting evidence argues that neurodevelopment defects
cannot be simply explained by alterations in the steady state level of cholesterol per se. Indeed, cholesterol precursors
and metabolites display biological activities towards signalling pathways that are important for neural development,
e.g. hedgehog signalling. Little is known about what type of sterols are produced during human neural development
and what roles they play. It is also important to find out how neuronal cells regulate their cholesterol homeostasis
during different developmental stages.
This studentship will combine state-of-the-art neural stem cell technology (Cardiff) and advanced mass spectrometry
(Swansea) to address these questions. The student will benefit from a multidisciplinary collaboration of two leading
laboratories. She/he will learn how to differentiate cortical neurons from human stem cells, immunostaining and
imaging analysis of neural cell markers. He/she will also learn how to identify and quantify sterol molecules using liquid
chromatography-mass spectrometry. The student will also be trained in other modern molecular biology techniques
to study gene expression, protein-DNA interactions and protein-protein interactions