Roles of the microcephaly and obesity-associated gene Trappc9 in the cellular regulation of lipid droplets and lipophagy

In this PhD project, you will investigate the cellular functions of the Trafficking protein particle complex subunit 9 (Trappc9), which is involved in vesicle trafficking and lipid droplet regulation. Mutations of Trappc9 in human and mice cause a neurodevelopmental disorder characterised by microcephaly, intellectual disability and obesity. Trappc9 is a subunit of the TrappII complex, and it has been shown that Trappc9-deficient cells form unusually large lipid droplets and have defects in fatty acid degradation. Using our Trappc9 knock-out mice, we found a reduced brain size 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 lipid droplet size, metabolism and lipophagy/autophagy mechanisms. Vesicle transport processes might also be investigated. You will be working mainly with primary cell cultures from this mouse line, e.g. neuron and neural stem cell cultures, fibroblasts and/or adipocytes. The work will involve specific fluorescent markers and advanced microscopy (confocal, live-cell imaging) as well as molecular biology techniques (e.g. sub-cellular fractionation, Western blotting). In collaboration with a partner laboratory at Newcastle University, we will also be investigating lipophagy mechanisms in these cells. As part of this training programme, you will spend three months in the partner laboratory at Newcastle University to acquire specific experimental skills in this field. Apart from lipid droplet physiology, other vesicle transport mechanism might also be investigated, for example retrograde transport in neuronal cells. In addition to the cell and molecular biology aspects, this project might further involve analysis of mouse tissues through histological and immunohistochemistry techniques.

Apart from these experimental skills, by the end of this PhD programme you will also have acquired 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.

Supervisors:

Dr. Antonius Plagge (plagge@liverpool.ac.uk)

https://www.liverpool.ac.uk/systems-molecular-and-integrative-biology/staff/antonius-plagge/

Dr. Viktor Korolchuk

https://www.ncl.ac.uk/medical-sciences/people/profile/viktorkorolchuk.html

HOW TO APPLY

Applications should be made by emailing bbsrcdtp@liverpool.ac.uk with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2^nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to bbsrcdtp@liverpool.ac.uk. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to plagge@liverpool.ac.uk

The deadline for all applications is 12noon on Monday 9^th January 2023.