Research Groups
Introduction
Blundell Brindle Broadhurst Brown Carrington Dupree Evan  Head of Dept. Farndale Gay Grace Griffin Hendrich Hesketh Higgins Hollfelder Hong Howe Hyvonen Jackson S Jackson T Jackson R Laue Leadlay Lester Lilley Lipkow	Livesey Luisi Lummis Mata McCafferty Metcalfe Mishima Miska Monie Mott Murzina Nietlispach Owen Oliver Packman Pellegrini Robinson Salmond Scadden Silva Smith A Smith C Standart Thomas Timmers Tolkovsky Welch Zhang
Past members

Application of Magnetic Resonance Imaging and Spectroscopy to Biology and Medicine

Research Groupings: Cancer | Structural and molecular cell biology | Medical imaging

A targeted MRI contrast agent that binds to apoptotic cells can be used to detect tumour cell death in vivo post-therapy.  The false colour image indicates contrast agent concentration, with the colder colours indicating a higher concentration.  The agent accumulates in a treated tumour (a), when compared to an untreated tumour (c), or in treated or untreated  animals injected with an inactive agent (b & d).  See larger image

Tumour Therapy
Magnetic resonance imaging (MRI) is a well-established and clinically applicable tool for determining tissue morphology. The techniques of molecular imaging seek, through the use of appropriate probe molecules, to transfer into the MR image of tissue anatomy, information about underlying tissue biochemistry and physiology. We are developing novel magnetic resonance-based molecular imaging techniques to detect the early responses of tumours to therapy, with a view to translating these into clinical application. This has included methods for detecting and predicting responses to an anti-vascular drug and for detecting early tumour responses to immunotherapy. An early apoptotic response following treatment with a chemotherapeutic drug is a good prognostic indicator for treatment outcome. Therefore, a major focus is the development of magnetic resonance imaging (MRI) and spectroscopy (MRS) methods for the non-invasive detection of tumour cell apoptosis in vivo.

Images of tumours before and after drug treatment.  The grayscale image shows tissue anatomy.  The false colour image indicates the activity of an enzyme in the tumour, which is decreased in dying cells (the less yellow the colour the lower the enzyme activity).  Enzyme activity was measured by a acquiring a series of images following injection of a hyperpolarized enzyme substrate. See larger image

Through a commercial partnership, we are developing nuclear spin hyperpolarization as a novel tool for molecular imaging. Nuclear spin polarization offers enormous gains in sensitivity, as much as 10,000x, which makes it possible not only to image the distribution of isotopically-labelled cellular metabolites, but also their enzymatic transformation into other species. This approach could revolutionise molecular imaging using MR techniques, giving new insights into disease processes in vivo.

Metabolomics
Metabolomics, the comprehensive analysis and quantification of the metabolite complement of cells or tissues, has an important role to play in studies of toxicology, the diagnosis of disease, and as a new tool for functional genomics.  We have shown that ¹H MRS-based metabolite profiling can be used to distinguish tumour cell lines in which the genes for specific transcription factors have been ablated.

Multivariate statistical analysis of the metabolite profiles obtained from yeast gene deletion mutants.  On this principal components plot, mutants with lesions in the same areas of cellular metabolism are grouped together.  Thus if the metabolic profile of a yeast strain with a mutation in a gene of unknown function is grouped with those of known function, then we propose that the function of the unknown gene can be inferred. See larger image

This approach may also be useful in the analysis of patient tumour biopsies, where the expectation is that it could be used to give information about drug sensitivity and prognostic information about treatment outcomes.  Our future goal is to use the same approach that we adopted in yeast to understand metabolic network structure in tumour cells and to use this information to understand the effects of specific drugs.

Prof. Brindle holds a joint appointment between the University and Cancer Research UK.  He also has another laboratory in the CRUK Cambridge Research Institute.

Lab members
Israt Alam, Sarah Bohndiek, Tom Booth, Joan Boren, Holly Canuto, Sarah Fawcett, Ferdia Gallagher, Arjun Goyal, Becky Harmston, De-En Hu, Brett Kennedy, Mikko Kettunen, David Lewis, Scott Lyons, Andre Neves, William O'Dell, Dmitri Soloviev, Henning Stöckmann, Sui Seng Tee, Tim Witney

References