BBSRC EASTBIO DTP: In vivo live imaging and multi-omic analysis of pre-neoplastic cell metabolic change

“Warburg metabolism” is characterised by an increased uptake of glucose and its conversion to lactate by glycolysis under normoxia. It is an important feature of cells under physiological/pathological stress such as immune cell activation during inflammation or cancer metabolism; moreover glycolysis is a characteristic of undifferentiated stem cells. To date, metabolic reprogramming of cancer cells has been recognized as a target for therapeutic intervention. However, it is unclear as to when and how metabolic changes occur during pre-neoplastic cell progression. We hypothesized that Warburg metabolism or metabolic change is an early event during pre-neoplastic cell initiation and plays an important role in supporting pre-neoplastic cell (PNC) progression. Until recently, it has been difficult to investigate PNC initiation and progression in vivo with precise spatiotemporal information due to limitations of available animal models. My lab has developed a tamoxifen-inducible system whereby fluorescent labeled PNCs can be induced in skin tissue with precise temporal control and their interaction with host tissues followed with live imaging. Using this model we have been monitoring PNC and innate immune cell interactions in vivo in real time. Our preliminary study using the Seahorse Analyzer® showed impaired mitochondria respiration and enhanced glycolysis in PNCs.

In the current project we seek first to characterize metabolic changes within the PNC niche, second to identify pathways in PNCs that are important for these metabolic alterations and finally to determine how metabolic alternations contribute to PNC progression.

Aim 1 Characterize metabolic alteration within the PNC niche
Aim 2 In vivo live imaging of metabolic alterations
Aim 3 Manipulating metabolic pathways within PNCs using a lineage specific Cas9 system
The PhD candidate will be part of a team working alongside a computational biologist and research assistant on the project.
Student training includes:
Wet lab: zebrafish genetic manipulation techniques, in vivo live imaging; Imaging Mass Spectrometry sample preparation and handling.
Computational lab: Cutting-edge analytical tools for single cell RNA-seq data analysis and interpretation; 4D imaging data analysis and Imaging Mass Spectrometry data analysis.

Applications:
Completed application form along with your curriculum vitae should be sent to our PGR student team at [Email Address Removed]

References:
Please send the reference request form to two referees. Completed forms for University of Edinburgh College of Medicine and Veterinary Medicine project should be returned to [Email Address Removed] by the closing date: 5th December 2018.

It is your responsibility to ensure that references are provided by the specified deadline.

Download application and reference forms via:
https://www.ed.ac.uk/roslin/postgraduate/bbsrc-eastbio-dtp