Lucy Flint, a final-year PhD student at the Biomolecular Sciences Research Centre (BMRC) at Hallam, has been working with AstraZeneca to successfully characterise a 3D cell culture model. It is hoped the research findings can assist in the development of new anticancer drugs. Analytical Chemistry, a scientific journal published by the American Chemical Society, will also be featuring the research on its upcoming front cover.

We have been speaking to Lucy about her research project.

Lucy Flint

​​​​​​​​​​​​​​How did your joint research project with AstraZeneca come about?

There has been a long-standing collaboration between Sheffield Hallam and AstraZeneca through previous part-time PhD students who are employees at AstraZeneca and were supervised by Professor Malcolm Clench, including Dr John Swales, who completed his PhD in MS imaging in 2018.

Can you tell us a little bit about what you were hoping to achieve?

My visit to AstraZeneca was a brilliant opportunity for myself to work in an established research laboratory and experience industry. My aim was to learn and develop skills of experimental procedures and the use of high-performance imaging instrumentation available at AstraZeneca to apply these techniques for the analysis of my 3D cell culture models. It was also hoped that I could generate high-quality data that could be published. Through my first visit I was able to establish the basis of the formal collaboration agreement for my project between Sheffield Hallam and AstraZeneca, with the aim of exchanging knowledge on MS imaging and 3D cell culture.

You mention 3D cell culture – can you explain this to us?

3D cell culture is an emerging method to study disease, helping to determine therapeutic targets in drug development. They are a product of a laboratory-created environment in which cells grow and interact with each other and their surroundings in three dimensions. This allows the cells to mimic the biological microenvironment of human tissues, promoting cell-cell interactions and the expression of essential molecules. The purpose of using 3D cell culture in scientific experiments is to create a realistic environment for drug testing whilst addressing the 3Rs principle, which is the reduction, replacement, and refinement of the use of animals in such research.

How did your own skills and experience help make the project a success?

I had been working on my PhD for 18 months prior to my first visit to AstraZeneca. During that time, I had developed my 3D cell culture models and practice MS imaging. Because of my experience of MS imaging, after instrument-specific training I was then able to carry out most of the experimental and analysis work independently at AstraZeneca. From the collaboration I was also able to bring my experimental skills and background of imaging 3D cell culture and specific MSI protocols for viewing peptides to the research group.

What were the main challenges you faced?

As I was using different instrumentation to analyse my 3D model, one of the main challenges was developing an experimental workflow for each method, considering the different sample preparation steps required for the appropriate technique. I further developed protocols that were originally established for animal or clinical tissues and optimised methods for my 3D lung tumour model. The next challenge was to actually mine through the large data sets from each technique, finding key molecules, their relevance to specific regions of the tissues and complementary links between the different data sets which took some time.

Analytical Chemistry front cover

Can you provide a summary of your findings?

In this paper, we used MS imaging to characterise our novel 3D model of lung cancer. This was with the purpose of understanding how these molecules within the tumour behave for potential applications in cancer research and drug development. MS imaging is a technique in which we can visualise a variety of molecules within a tissue without the use of labels. By determining the spatial information of a molecule, such as if the molecule is localised to a specific area or distributed throughout, we can understand the biological functions and interactions within a tissue.

We were able to show that the lung tumour model had a similar structure to a human solid tumour with three distinct regions. This is significant in terms of drug delivery because it is difficult to deliver drug to the inner region of a solid tumour, and the fact that our model replicates this shows that it is a useful tool for drug development.

What is the next step for the project?

Now that we have characterised the 3D lung tumour model, we want to demonstrate the capabilities of this method for drug development applications by studying biopharmaceutical effectiveness. We aim to utilise the techniques we have developed to detect and quantify a commercial anticancer drug, Cetuximab, within the 3D model and determine its effects.

And finally, how did you feel about your research being recognised by Analytical Chemistry?

It is a really great feeling! Analytical Chemistry is a well-established journal, so to have my work recognised by them is very exciting. I am extremely passionate about MS imaging and 3D cell culture, so I hope it will open up a lot of opportunities. Since my paper has been published, I have had a lot of interest and one of my images is going to be featured on the front cover of the journal issue. I really enjoyed doing the work and I am proud of my paper, so it is an amazing feeling to see its success.