Optical Molecular Imaging

Over the past 10 years the Bradley group has had a very close relationship with the groups of Professor Chris Haslett and Dr Kev Dhaliwal (both in the Medical School) in the area of Optical Molecular Imaging.

The driver for all the activity in this area is clinical pull and need – working with clinicians on a day-to-day basis. The ambition and desire is to translate into man to provide clinicians with enhanced information on disease status.

• The team’s first reagent (from bench to beside) has entered first-in-man trials.
• The team has set up its own GMP production facility.

One of our main research lines is focused in the field of optical imaging, in collaboration with Prof. Haslett and Dr. Dhaliwal groups (MRC/Centre for Inflammation Research, University of Edinburgh). The aim of this multidisciplinary research programme is the development of ‘smart probes’ for the non-invasive fluorescent imaging of key targets in several diseases including cancer, inflammatory disease and cystic fibrosis. The ability to use this approach to specifically monitor the presence of a pathogen, the activity of an enzyme or other biological processes, in a non-invasive manner at the target organs would aid early diagnosis and enable stratification of patient care. This approach also allows the rapid design and testing of new drugs.

Different projects in this area are being funded by MRC, WT and EPSRC. As a result, "smart" probes for Human Neutrophil Elastase and activated neutrophils to detect lung inflammation in real time have been developed and led to the first "smart" probe for human use with Optical Confocal Laser Endomicroscopy (OCLE) filing the first patent in the area.

Other projects in course are aimed to create novel active chemical "smart" probes for detection or bacteria, and optical molecular probes for the in situ measurement of different biomarkers in fibrosis.

Most recently, the Bradley group has developed probes for neutrophil imaging shown by the following image.

neutrophil imaging

Recent papers include:

1) In situ identification of Gram-negative bacteria in human lungs using a topical fluorescent peptide targeting lipid A
A. R. Akram, S. V. Chankeshwara, E. Scholefield, T. Aslam, N. McDonald, A. Megia-Fernandez, A. Marshall, B. Mills, N. Avlonitis, T. H. Craven, A. M. Smyth, D. S. Collie, C. Gray, N. Hirani, A. T. Hill, J. R. Govan, T. Walsh, C. Haslett, M. Bradley and K. Dhaliwal

2) Enhanced avidity from a multivalent fluorescent antimicrobial peptide enables pathogen detection in a human lung model
A. R. Akram, N. Avlonitis, E. Scholefield, M. Vendrell, N. McDonald, T. Aslam, T. H. Craven, C. Gray, D. S. Collie, A. J. Fisher, P. A. Corris, T. Walsh, C. Haslett, M.Bradley and K. Dhaliwal

3) Bimodal fluorogenic sensing of matrix proteolytic signatures in lung cancer
Megia-Fernandez, B. Mills, C. Michels, S. V. Chankeshwara, N. Krstajić, C. Haslett, K. Dhaliwal and M. Bradley

4) Super-silent FRET Sensor Enables Live Cell Imaging and Flow Cytometric Stratification of Intracellular Serine Protease Activity in Neutrophils
Craven, T.H., Avlonitis, N., McDonald, N. et al.

5) A Labelled-Ubiquicidin Antimicrobial Peptide for Immediate In Situ Optical Detection of Live Bacteria in Human Alveolar Lung Tissue
Akram, A. R., Avlonitis, N., Lilienkampf, A., Perez-lopez, A. M., Mcdonald, N., Chankeshwara, S. V., Scholefield, E., Haslett, C., Bradley, M. & Dhaliwal, K.

6) Wash‐free, peptide‐based fluorogenic probes for microbial imaging
A. Baibek, Muhammed Üçüncü, E. A. Blackburn, A. Lilienkampf and M. Bradley

7) Polymyxin-based photosensitizer for the potent and selective killing of Gram-negative bacteria
M. Ucuncu, B. Mills, S. Duncan, Matteo Staderini, Kevin Dhaliwal and M. Bradley

8) In-situ imaging of neutrophil activation in the human alveolar space with neutrophil activation probe and pulmonary optical endomicroscopy
T. Craven, T. Walton, A. Akram, N. McDonald, E. Scholefield, T. Walsh, C. Haslett, M. Bradley and K. Dhaliwal

Further Information

Professor Bradley is the principal investigator of the EPSRC project PROTEUS in Optical Imaging and Sensing. This £11.3M project is an Interdisciplinary Research Collaboration and involves some 18 post-docs and some 10 research groups that includes groups in optical physics, chemistry, biology and informatics. There are also some 20 PhD students working in the PROTEUS project.

Proteus (http://www.proteus.ac.uk) - funded by EPSRC

The company Edinburgh Molecular Imaging was spun-out in 2014 as a result of the team's work in the area of Optical Imaging Probes.

Edinburgh Molecular Imaging (http://www.edinimage.com/)

• Professor Mark Bradley is principal Investigator of the EPSRC and MRC CDT in Optical Medical Imaging which has been established to ensure that the UK has a strong and sustained pipeline of future scientific leaders and innovators in optical medical imaging encompassing the molecular, cellular, preclinical and clinical applications of physical and biomedical science in this priority area. 60 PhD students will be recruited over the following five years with the programme running for eight years.

In conjunction with OPTIMA CDT (http://www.optima-cdt.ac.uk/) - funded by EPSRC and MRC

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