The hypothalamus is now recognised as a neurogenic niche in the adult rodent brain, with radial glial-like cells, termed tanycytes, serving as its resident neural stem cells. Tanycytes add new neurons to the hypothalamic circuitry that controls appetite/ energy expenditure, suggesting that these circuits can be modulated. Identifying factors that regulate tanycyte biology and postnatal hypothalamic neurogenesis therefore will be beneficial to strategies for regulating appetite/energy expenditure and tackling eating disorders. Fibroblast Growth Factors (FGFs) have emerged as strong putative modulatory candidates, but their role/s and mode of action remains unknown.
This project draws on the recent discoveries that region-specific brain organoids can be generated in vitro to study the intricate steps of neurogliogenesis. However, hypothalamus is less well explored and thus the project aims to generate both ex vivo whole organ models as well as ips-derived hypothalamic stem cells. Existing organoid recipes and novel tissue isolation approaches will be integrated to generate ex vivo and in vitro models and the successful model will be used to dissect the role of several FGF signalling molecules in directing tanycyte division, survival and differentiation into specific neuronal populations, using FGF knockdown and overexpression strategies.
We seek a highly motivated candidate with a background in neurobiology, developmental biology or closely related subjects. The candidate will be trained in a range of concepts and techniques, including fine brain dissection, ips, tissue and cell culture, immunofluorescence labelling, time-lapse microscopy, image analysis, transgenic mouse biology, neuroanatomy and neural stem cell biology. Moreover, through generic and tailor-made packages, the candidate will acquire a set of transferrable skills, ranging from statistical analysis of biological data to delivering effective presentations, science communication and leadership. The project has the potential to provide the candidate with high impact publication/s and prepare him/her for a research career in neurosciences.