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Details of Grant 

EPSRC Reference: EP/T011637/1
Title: A bottom-up approach to the rational design of new bioluminescence emitters
Principal Investigator: Fielding, Professor H
Other Investigators:
Worth, Professor GA Anderson, Professor JC
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: UCL
Scheme: Standard Research
Starts: 01 July 2020 Ends: 31 July 2024 Value (£): 1,373,812
EPSRC Research Topic Classifications:
Physical Organic Chemistry
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
11 Sep 2019 EPSRC Physical Sciences - September 2019 Announced
Summary on Grant Application Form
This research will improve our molecular level understanding of bioluminescence for the rational design of new near-infrared emitters for advanced bioluminescence imaging applications.

Bioluminescence is the emission of light by living organisms. It is one of Nature's most spectacular phenomena and continues to challenge those who try to understand it. The yellow-green glow of fireflies is one of the brightest and most beautiful examples of bioluminescence. The biochemical process involves the catalytic oxidation of a small molecule (luciferin) by an enzyme (luciferase) to form an electronically excited oxyluciferin that subsequently relaxes to its ground state by emitting light.

Harnessing bioluminescence for imaging applications has revolutionised the biosciences. Bioluminescence imaging is now a standard tool for visualising molecular and cellular processes in vivo. However, more advanced applications are limited by reduced sensitivity in deep tissue arising from the absorption of visible light by blood and tissue. New far-red and near-infrared bioluminescence systems for enhanced sensitivity and resolution in deep tissue have recently become available; however, they are limited by their brightness and narrow spectral range. There is a pressing need for bright, multicolor, far-red and near-infrared emitters.

To date, modifications to bioluminescent systems have relied on incremental changes and small library-based approaches. We propose to use a fundamentally new, bottom-up approach. We will use state-of-the-art spectroscopy measurements and quantum chemistry calculations to learn which electronic states and molecular motions of far-red and near-infrared luciferins are important in the competing non-radiative relaxation pathways that reduce the brightness of bioluminescence and we will learn how luciferase enzymes tune the bioluminescence wavelength. We will then use this information to design new, bright bioluminescent emitters for multicolour, far-red and near-infrared bioluminescence imaging.
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