Expanding the possible: Expansion microscopy of tumour spheroids to examine genome instability and molecular effects of DNA-damaging therapeutics in 3D culture.

The Opportunity

This 3.5 year, North West Cancer Research funded, PhD presents the opportunity to join our interdisciplinary team applying advanced imaging techniques to cancer research.

Background

Most cell biology and cancer research to date has been carried out in 2D cell cultures. However, 3D models of cancer cell growth are more physiologically relevant in both understanding the biology of cancer and in assessing the efficacy of cancer therapeutics. Researchers, including ourselves, have been optimising the culture of “tumour spheroids” as cancer-relevant 3D models. However, although excellent physiological models, they are challenging to image at high resolution, often limiting outputs to simple parameters.

To overcome this limitation, we have developed a robust and reproducible Expansion Microscopy (ExM) protocol for tumour spheroids, a first of its kind. ExM works by physically enlarging samples, allowing the interrogation of cellular ultra-structures normally beyond the resolution limit of light microscopy. Importantly, we also show the technique allows robust penetration of both probes and antibodies into the spheroid core, revealing previously inaccessible molecular details in 3D.

Your Project

In this project, you will harness the power of this new technique to assess parameters key to understanding cancer biology, and the mechanism of action of therapeutics, as well as examining drug penetration and pharmacology throughout the depth of the spheroids.

The project will focus on Head and Neck Squamous Cell Carcinoma models, which we already have significant research expertise with, including well-established methods to grow HNSCC spheroids.

In addition to the laboratory research, a key output of the project will be a workshop to share the technique and findings with other cancer researchers in the North-West, which will be an excellent opportunity for you to showcase your work to leaders in the field as you approach the end of your PhD.