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Details of Grant 

EPSRC Reference: EP/T002123/1
Title: MEGA-FLIM: quantum technologies for megapixel time-resolved imaging and control across biological scales
Principal Investigator: Machesky, Professor L
Other Investigators:
Faccio, Professor DFA Insall, Professor R Harvey, Professor A
Gadegaard, Professor N Taylor, Dr J
Researcher Co-Investigators:
Project Partners:
Department: College of Medical, Veterinary, Life Sci
Organisation: University of Glasgow
Scheme: Standard Research
Starts: 01 April 2019 Ends: 31 March 2022 Value (£): 1,875,030
EPSRC Research Topic Classifications:
Analytical Science Biophysics
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
19 Mar 2019 Building Collaboration at the Physics of Life Interface Announced
Summary on Grant Application Form
Embryos, organs and tumours are composed of many cells, which interact with each other and communicate across distances of several cells. While it is routine to study single cells under a microscope, it is much more difficult to study collectives due to their size, light scattering properties and complexity. Fluorescence lifetime imaging (FLIM) and FRET (Forster resonance energy transfer) use the principles of energy transfer that occur when a light particle (photon) jumps from an excited fluorescent donor molecule to a nearby acceptor, thus changing the fluorescence lifetime of the donor. FLIM is used to measure close molecular interactions inside of living cells by measuring this lifetime change. We will combine physics, engineering, computation and biology to build a new light microscopic system, with extremely high spatial and temporal resolution. We call our system MEGA-FLIM and we will use it to study larger cell collectives of cells to discover how cells communicate and organise in response to both mechanical and chemical signals. MEGA-FLIM will allow much faster collection of light signals across a much larger field than previously possible. We will also develop technology to use light to control cell behaviour across these collectives using the technique called optogenetics. Our unique team of optical physicists, bioengineers and biologists is ideally placed to break down current barriers, leading to landmark discovery in each of these fields.

Why do we need a new FLIM microscope system?

Commercial systems are lacking that allow, simultaneously:

- fast acquisition (0.1 second or faster) so as to allow real-time measurements in live cells or embryos

- across a widefield area with high resolution (1 million pixels or higher), so as to allow imaging of the full cell environment and large collectives

- with high time resolution (50-100 pico seconds), so as to allow precise discrimination of lifetimes

- two-photon excitation, so as to allow precise full 3D reconstruction of cell collectives.

- widefield optogenetic activation (light-controlled cell behaviour), so as to allow study of the dynamics of collectives in the presence of complex activation stimuli that act across multiple sites.

What problems will this new system solve and what impact will it have?

-MEGA FLIM will provide a system that will allow us to interrogate living systems at molecular resolution and discover how cells collectively signal using both chemical and mechanical signals to steer when they migrate. This kind of steering allows cells to recognise each other and other cell types and to form complex patterns in 3 dimensions (like in an organ or an embryo).

-Our new system will be of great commercial interest, as it will advance capabilities in imaging and optogenetic control of cell behaviour with light.

-By building a system whereby we can discover new pathways governing how cells behave in collectives, we will gain the ability to reliably and predictably control collective cell behaviour. This discipline, known as synthetic biology, is highly desirable for medical and commercial use in building organ/tumour-on-chip systems or creating physiologically relevant systems to use in drug discovery.

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Organisation Website: http://www.gla.ac.uk