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Mass spectrometry imaging

Cancer Grand Challenges: Rosetta Project

Overcoming the biggest challenges in a global effort to beat cancer sooner through collaboration

Through Cancer Research UK's Grand Challenge programme, NPL's Professor Josephine Bunch leads a team of multidisciplinary chemists, physicists and biologists from across the UK. We deliver new insights which have the potential to revolutionise our understanding of cancer and pioneer more effective treatments.  

The team are developing reproducible, standardised methods to fully map tumours with unprecedented detail and precision. This is delivering extraordinary results, opening the door to new and better ways to diagnose, treat and manage cancer.  

The information unlocked by the Rosetta pipeline provides a much deeper understanding of cancer, which could offer a radical change in clinical decision making at every point of the patient journey. This enables us to define new targets for diagnosis, therapy and prognosis.

Josephine Bunch - Principal Investigator on the Rosetta project and NPL Fellow

Sharing the outputs from Rosetta

The goals of Rosetta are delivered through the development of multimodal molecular imaging technologies, centred on mass spectrometry. These technologies are supported by advanced bioinformatics tools that enable us to map, characterise and understand cancer metabolism in unprecedented detail.  

The Rosetta team has achieved substantial advances in the technologies needed to achieve the programme’s objectives. Research to date has enabled new analytical imaging techniques, enhanced lasers and ionisation approaches and new approaches to sample handling. This will allow us to analyse the millions of tumour samples held in biobanks around the world. Dissemination of the Rosetta team’s research has been a key part of the programme, enabling the global cancer research community to benefit from the team’s work.

To achieve this we have delivered:  

  • Peer-reviewed scientific papers 

  • A multidisciplinary team of researchers tackling the challenge, directly or in collaboration with the team since its inception in 2017

  • An MSI pipeline integrated into around 85% of AstraZeneca's drug development projects

  • More than 100 talks and presentations at scientific conferences around the world

The 'Rosetta Stone' of cancer cell metabolism

In the same way cartographers build maps of cities and countries to help people get around, scientists build maps of tumours to better understand their inner workings. But our tumour maps remain incomplete. What has been missing is our ability to see down to the very core of cancer cells and understand how changes in their metabolism can impact their overall state and function within a tumour. No one has ever mapped tumours to this level of detail – until now. 

The Rosetta team have initially focused on breast, bowel and pancreatic tumours, as well as investigating an aggressive type of brain tumour. They are working to capture changes to metabolites as tumours develop or respond to treatments, while simultaneously recording information about the cell's exact location within the tumour. 

Superimposing this data with maps revealing information about the underlying genetics of these cells will produce is enabling our research team to assemble the world's first 'Rosetta Stone' of cancer cell metabolism. This will be a high-resolution metabolic “map” that offers unprecedented insight into a cell's biochemical state. This cutting-edge approach is generating vast amounts of data, which will be made freely available to the research community, providing a Google Earth-type view of a tumour, on a scale that we have never known before. 

The Rosetta Project

                         

Contact us

 

Meet the team

Grand Challenge team

I'm very excited about the progress we have made. We now have data to suggest that the major mutation that occur in colorectal and pancreatic cancer drives a metabolic signature that can be easily identified using image-based mass spectrometry approaches. This demonstrates the power of this methodology to stratify cancers. Going forward I'm looking forward to discovering if we can see if we can use these approaches to predict therapeutic responses in these cancers.

Professor Owen Sansom - Beatson Institute

A global collaboration - the work has featured in many recent publications:

Bunch J, Steven R, Taylor A, Thomas S, Race A, Dexter A, ... Takats Z. (2018). Abstract 5661: A multi modal mass spectrometry imaging strategy to profile the metabolic hallmarks of colorectal cancer.
doi: 10.1158/1538-7445.AM2018-5661

Colclough N, Chen K, Johnström P, Strittmatter N, Yan Y, Wrigley GL, ... Cross DAE. (2020). Preclinical Comparison of the Blood-brain barrier Permeability of Osimertinib with Other EGFR TKIs. Clinical cancer research : an official journal of the American Association for Cancer Research,
doi: 10.1158/1078-0432.CCR-19-1871

Dannhorn A, Kazanc E, Ling S, Nikula C, Karali E, Serra MP, ... Takats Z. (2020). Universal Sample Preparation Unlocking Multimodal Molecular Tissue Imaging. Analytical chemistry, 92(16), pp. 11080-11088.
doi: 10.1021/acs.analchem.0c00826

Dexter A, Thomas S, Steven R, Robinson K, Taylor A, Elia E, ... Bunch J. (2020). Training a neural network to learn other dimensionality reduction removes data size restrictions in bioinformatics and provides a new route to exploring data representations.

Elia EA, Niehaus M, Steven RT, Wolf JC, Bunch J. (2020). Atmospheric Pressure MALDI Mass Spectrometry Imaging Using In-Line Plasma Induced Postionization. Analytical chemistry, 92(23), pp. 15285-15290.
doi: 10.1021/acs.analchem.0c03524

Fala M, Somai V, Dannhorn A, Hamm G, Gibson K, Couturier DL, ... Goodwin RJA & Brindle K. (2020). Comparison of 13C magnetic resonance images of hyperpolarized [1-13C]pyruvate and lactate with the corresponding mass spectrometry images in a murine lymphoma model. Magnetic Resonance in Medicine,

Flint LE, Hamm G, Ready JD, Ling S, Duckett CJ, Cross NA, ... Clench MR. (2020). Characterization of an Aggregated Three-Dimensional Cell Culture Model by Multimodal Mass Spectrometry Imaging. Analytical chemistry, 92(18), pp. 12538-12547.
doi: 10.1021/acs.analchem.0c02389

Goodwin RJA, Takats Z, Bunch J. (2020). A Critical and Concise Review of Mass Spectrometry Applied to Imaging in Drug Discovery. SLAS discovery : advancing life sciences R & D, 25(9), pp. 963-976.
doi: 10.1177/2472555220941843

Hulme H, Meikle LM, Strittmatter N, van der Hooft JJJ, Swales J, Bragg RA, ... Wall DM. (2020). Microbiome-derived carnitine mimics as previously unknown mediators of gut-brain axis communication. Science advances, 6(11), pp. eaax6328.
doi: 10.1126/sciadv.aax6328

Koundouros N, Karali E, Tripp A, Valle A, Inglese P, Perry NJS, ... Poulogiannis G. (2020). Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids. Cell, 181(7), pp. 1596-1611.e27. doi: 10.1016/j.cell.2020.05.053

Koundouros N, Poulogiannis G. (2020). Reprogramming of fatty acid metabolism in cancer. British journal of cancer, 122(1), pp. 4-22.
doi: 10.1038/s41416-019-0650-z

Koundouros N,, Tripp A, Karali E, Valle A, Inglese P, Anjomani-Virmouni S, ... Poulogiannis G. (2019). Near real-time stratification of PIK3CA mutant breast cancers using the iKnife. 211th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland.

Kreuzaler P, Panina Y, Segal J, Yuneva M. (2020). Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion. Molecular Metabolism,
doi: 10.1016/j.molmet.2019.08.021

Mair R, Wright AJ, Ros S, Hu DE, Booth T, Kreis F, ... Brindle KM. (2018). Metabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma. Cancer research, 78(18), pp. 5408-5418.
doi: 10.1158/0008-5472.CAN-18-0759

Moss J, Barjat H, Emmas S, Strittmatter N, Maynard J, Goodwin R, ... Barry S. (2020). High-resolution 3D visualization of nanomedicine distribution in tumors. Theranostics, (2),
doi: 10.7150/thno.37178

Najumudeen AK, Ceteci F, Fey SK, Hamm G, Steven RT, Hall H, ... Sansom OJ. (2020). The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer. Nature Genetics,

Niehaus M, Robinson KN, Murta T, Elia EA, Race AM, Yan B, ... Bunch J. (2020). MALDI-2 at Atmospheric Pressure-Parameter Optimization and First Imaging Experiments. Journal of the American Society for Mass Spectrometry, 31(11), pp. 2287-2295.
doi: 10.1021/jasms.0c00237

Ros S, Wright AJ, D'Santos P, Hu DE, Hesketh RL, Lubling Y, ... Brindle KM. (2020). Metabolic Imaging Detects Resistance to PI3Kα Inhibition Mediated by Persistent FOXM1 Expression in ER Breast Cancer. Cancer cell, 38(4), pp. 516-533.e9.
doi: 10.1016/j.ccell.2020.08.016

Schuijs M, Png S, Richard A, Tsyben A, Hamm G, Stockis J, ... Halim T. (2020). ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung. Nature Immunology, (9),
doi: 10.1038/s41590-020-0745-y

Seth Nanda C, Venkateswaran SV, Patani N, Yuneva M. (2020). Defining a metabolic landscape of tumours: genome meets metabolism. British journal of cancer, 122(2), pp. 136-149.
doi: 10.1038/s41416-019-0663-7

Smith AL, Whitehall JC, Bradshaw C, Gay D, Robertson F, Blain AP, ... Greaves LC. (2020). Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis. Nature cancer, 1(10), pp. 976-989.
doi: 10.1038/s43018-020-00112-5

Tzafetas M, Mitra A, Paraskevaidi M, Bodai Z, Kalliala I, Bowden S, ... Kyrgiou M. (2020). The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease. Proceedings of the National Academy of Sciences, (13),
doi: 10.1073/pnas.1916960117

Upendra Rao J, Gibson K, Hamm G, Wright A, Fala M, Mair R, ... Brindle K. (2019). CBMT-33. VISUALIZING THE METABOLISM OF GLIOBLASTOMA PATIENT-DERIVED ORTHOTOPIC XENOGRAFTS BY MASS SPECTROMETRY IMAGING. Neuro-Oncology, (Supplement_6),
doi: 10.1093/neuonc/noz175.155

Yan B, Murta T, Elia EA, Steven RT, Bunch J. (2020). Direct Tissue Mass Spectrometry Imaging by Atmospheric Pressure UV-Laser Desorption Plasma Postionization. Journal of the American Society for Mass Spectrometry,
doi: 10.1021/jasms.0c00315