Investigating the cellular functions of Trappc9 in brain development and microcephaly

Description

This PhD project will investigate the cellular functions of the Trafficking protein particle complex subunit 9 (Trappc9) and its roles in brain development. Mutations of Trappc9 in human and mice cause a neurodevelopmental disorder characterised by postnatal microcephaly, intellectual disability and obesity. Trappc9 is a subunit of the TrappII complex, which is involved in regulating vesicle trafficking and cellular lipid droplets (LDs). Using our Trappc9 knock-out mice, we found a reduced brain size, differences in neuronal LD size and LD-associated proteins as well as increased body weight and enlarged adipocytes.

This project aims to investigate the underlying cellular defects that cause these phenotypes, especially how neurons, neural stem cells and the brain are affected by the mutation. The project will mainly use cell and molecular biological approaches to analyse the roles of Trappc9 in regulating LD size and mechanisms of lipid metabolism. You will be working with neuronal cell cultures, fibroblasts and/or adipocytes. The project will also utilise the new technology of brain organoid cultures derived from Trappc9 WT/KO mouse embryonic stem cells. Techniques will involve specific fluorescent markers and advanced microscopy (confocal, live-cell imaging) as well as various molecular biology techniques, e.g. qRT-PCR, Western blotting. Apart from lipid droplet physiology, vesicle transport processes might also be investigated, for example retrograde transport in neuronal cells. In addition to the cell and molecular biology aspects, this project might involve analysis of mouse tissues through histology and immunohistochemistry. Furthermore, throughout this PhD programme you will acquire training in quantitative skills, statistical analysis, data presentation and software applications for biosciences (e.g. image analysis, Python, R) through courses at the University of Liverpool.

The project is suited to a student with at least a good B.Sc. (Upper Second) in Biological or Life Sciences (e.g. Biomedical Sciences, Biochemistry, Physiology, Molecular Cell Biology, Neurobiology). 

Applications will be reviewed until a suitable candidate is appointed. The deadline is therefore subject to change, and applicants are encouraged to submit their application as soon as possible.