A multiphoton confocal microscope for deep tissue imaging in live organisms

Abstract

We are a team of scientists at King's College London who wish to buy a specialist microscope that can image tiny structures in living organisms, such as blood vessel walls or nerve processes.
This particular microscope is specially adapted to allow researchers to analyse events that occur deep within tissues, which are usually not accessible using normal research microscopes. It is also adapted to prevent any damage occurring from the imaging protocols we use, so we can visualise cell and tissue behaviour without affecting their function.
We would use this microscope to conduct research in many different areas of biological science, including immunology, tissue organisation and neuroscience. We will be able to image individual cells within organs, analyse their interactions with other cells and compartments and determine how these cells respond to wounds or pathogens.
Our results will help us understand more about how our bodies work, how we combat normal everyday infections and how our cells and tissues change during ageing.
The microscope would be placed within a purpose-built facility that has highly trained, dedicated staff to look after it. They will train other people how to use it in future for their own research questions. This means that the instrument would not only benefit our team, but also other scientists at our university and beyond.

Technical Summary

This bid proposes the installation of a new upright multiphoton microscope for intravital imaging at King's College London. It will be used by a multidisciplinary research community, including students and early-career researchers. Our team includes immunologists, cell and developmental biologists, neuroscientists, and imaging specialists, spread across multiple departments and campuses. We have significant expertise in intravital and tissue imaging, and in management of advanced imaging instruments within our core microscopy facility, where this instrument would be located.

This two-photon confocal microscope represents the state-of-the-art in deep tissue imaging, including advanced sensitive detectors, tuneable laser source for flexible wavelength applications, large field of view and automated 3D imaging. We can use it to leverage our expertise and skills to answer a diverse set of mechanistic questions, for example, through imaging of leukocyte recruitment, platelet motility, epithelial tissue integrity, extracellular matrix remodelling, neuro-immune interactions and activity in central nervous system circuitry.

Our findings will provide critical insight into the dynamic interplay between cells and tissue architecture, and how homeostasis is maintained following external insult. Our results will thus accelerate scientific progress in BBSRC strategic priority areas. Specifically, our work will be collaborative, in keeping with the 3Rs, and contribute to our understanding of the 'rules of life' and 'healthy ageing across the life course'.

Finally, by virtue of its accessible location, the microscope will be available to the wider community of scientists at King's and beyond, with excellent technical support and training readily available for future users.

Publications

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