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Cancer Grand Challenges Rosetta Project

The Rosetta Project

Find out more about the Rosetta project

Using the best imaging techniques to understand cancer

The team uses a variety of new mass spectrometry imaging techniques and instruments they've developed to study individual breast, bowel and pancreatic tumours; the cancers where they believe they can make the biggest difference, fastest. From the whole tumour right down to the individual fats and proteins in cells (the metabolites), to the tumour microenvironment, they will map and visualise every bit of these tumours to create faithful 3D representations of them for the first time. By doing this, they aim to create the equivalent of a 'Google Earth' that will allow you not only to identify a house and where it is in a country, but also who's inside, what they're eating and watching on TV.

The project so far

May 2017

Cancer Grand Challenges Rosetta Programme commences

December 2017

Full team of researchers is recruited

A team is recruited, uniting physicists, biologists and chemists with technology innovators and industry partners. 

May 2018

Proof-of-principle of Rosetta’s new imaging pipeline

The pipeline can successfully map the distribution of drugs within a tumour, including islands of drug resistance, and visualise changes in cellular metabolism. Their approach could be used to identify potential drug targets or to stratify patients according to their tumour biology.

Mid 2019

A wealth of historical preserved tissue is made accessible for analysis

The iKnife is a handheld device that uses rapid evaporative ionisation mass spectrometry (REIMS) to discriminate between healthy and malignant tissues. Having previously used fresh samples, the team shows that a similar quality of metabolic information can be attained from preserved tissue, making a wealth of historical preserved tissues accessible for analysis. 

May 2019

30% reduction in sample and data analysis time

A refinement of technology improves throughput of imaging pipeline meaning the team achieves an impressive 30% reduction in sample and data analysis time, primarily through automated processing, image segmentation and feature reporting. This makes the pipeline more practical for use in academic, clinical and commercial settings, for example to aid drug development. 

June 2020

Identification of a new metabolic signature   

Characterising a new metabolic signature in mouse breast cancer cells – enhanced arachidonic acid production – identifies a link between dietary fat and a tumour’s response to treatment. The change can be detected using the iKnife and correlates with a mutation in the PI3KCA gene, commonly mutated in breast cancer.

Besides highlighting the potential for metabolic phenotyping in stratified medicine, the study reveals an important role for activated PI3K signalling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction.

January 2021

A new role for SLC7A5 in KRAS-driven colorectal cancer

Using their multimodal imaging pipeline, the team identified the role of glutamine antiporter SLC7A5 in KRAS-driven colorectal cancer, for which treatment options are currently limited. Targeting SLC7A5 could provide a novel treatment avenue, exploiting tumour cells’ metabolic needs while having little impact on normal tissue.

Mutant KRAS is common in colorectal cancer, usually associated with poorer survival and increased tumour aggressiveness and often co-occurring with inactivation of the APC tumour suppressor. The team shows that co-mutation of apc and kras profoundly rewires metabolism in mouse intestinal epithelium, increasing glutamine consumption. SLC7A5 supports the increased metabolic demand and subsequent proliferation of these tumour cells by maintaining intracellular amino acid levels.

Thanks to Grand Challenge, we've been able to build a collective force of physicists, chemists and biologists – all coming together for the first time to map cancer in unprecedented detail. Our goal is to find out how tumours survive and why they keep growing. By applying our powerful analysis techniques to this problem, we want to gain new insight into these fundamental processes and develop new and better ways to diagnose and treat cancer

Dr Josephine Bunch - Lead Investigator, NPL

Multidisciplinary collaboration driving new discoveries

The future of science lies in the hands of the next generation of researchers. Cancer Grand Challenges aims to develop a cohort of brave, daring future leaders who are willing to unite and challenge the status quo – whatever their discipline and wherever they are in the world. Chelsea Nikula (chemist and higher research scientist) and Rory Steven (analytical chemist and senior research scientist), two early-career researchers helped identify SLC7A5 as a target for KRAS-driven colorectal cancer, answered questions about the project.

What is your role within the Rosetta team and this project?

Chelsea: I’m a chemist working in mass spectrometry imaging (MSI). For this particular work, I used matrix assisted laser desorption ionisation (MALDI) and desorption electrospray ionisation (DESI) MSI to analyse samples before assisting in the data processing. I’m very interested in how we can apply MSI techniques to the investigation of complex biological systems.

Rory: I’m an analytical chemist, working primarily in the fundamentals of MSI and its application in biological research. My contribution to this work has been acquiring MALDI and DESI MSI data, associated data analysis and helping to coordinate communications between team members and institutions.

How has the multidisciplinary, collaborative nature of the Rosetta team contributed to these findings and the team’s work?

Rory: A huge part of working on a large interdisciplinary project is effective communication – both in the context of technical discussions and on a more administrative level. Learning to speak one another’s language is key. It’s here that many of the challenges of interdisciplinary working occur, but the benefit of these interactions is massive. As an analytical scientist, I depend on the knowledge and insight our biologically focussed partners bring.

Chelsea: Having close working collaborations with cancer biologists, data scientists, chemists and physicists within our Cancer Grand Challenges team is incredibly beneficial, bringing unique perspectives to the complex datasets we produce. The mix of expertise enhances the interpretation of our results and means we gain a better understanding of our MSI data in relation to biological impact – which is absolutely crucial when forming hypotheses and conclusions. This paper illustrates the high impact science that can be achieved through highly multidisciplinary collaborations.

How have you found being part of a Cancer Grand Challenges team?

Chelsea: Being such a large, multidisciplinary team, there was definitely a learning curve at first, learning each other’s models, analytical techniques and methods of data processing. We’ve learnt how to present data to each other to facilitate understanding and discussion – I find it very rewarding, both intellectually and personally. I enjoy engaging with experts from a variety of areas, learning from them while sharing my passion for MSI. What an amazing experience!

Rory: Rewarding, challenging, exciting, frustrating, confusing… and a wonderful opportunity to be part of a unique and internationally leading community. I believe the most important work is done in multidisciplinary scenarios, so I really value the opportunity to work in this setting.

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