Purchase of a confocal microscope for Plymouth Light Microscopy Services (PLiMS) at Peninsula Medical School

We apply for the purchase of a specialised microscope for the light microscopy core facility at the Derriford Research Facility (DRF), Faculty of Health, University of Plymouth.
In 2017 the University of Plymouth opened the DRF next to the University Hospitals Plymouth NHS Trust. This major investment by the University strengthened and facilitated its medical research by locating medical and biomedical teams into the same building. The location next to the hospital was chosen to underpin the translational character of the investigations from basic molecular discoveries to clinical trials to find and establish new treatments. Our teams' research falls into the remit of the MRC, focusing on infection and immunity, molecular and cellular medicine, neurosciences and mental health, antimicrobial resistance, obesity research and regenerative medicine and stem cells.
Due to our national and international success the DRF grew significantly since its opening. The research accomplishments of our scientists depend on the use of highly specialised microscopes, confocal microscopes. These machines yield precise images of molecules in biopsies and other samples which are necessary not only for the diagnosis and study of diseases but also to follow efficacy of treatments. Currently, we have two confocal microscopes serving 44 researchers, of which one is already 10 years old and the other is a 5-year old basic model. Both are heavily used, with a waiting time of 14 days for either. This severely hampers progress of our research and discovery of new treatments. A third confocal microscope will shorten our waiting times to 2 to 3 days. Critically, we not only need a new machine to strengthen existing research but we want to look into the future and enter new research avenues to stay competitive and productive. The proposed microscope is equipped with a new state-of-the-art laser, novel high-sensitive detectors and a novel laser application allowing to gain insight into deep tissues. These are the features we identified as required to be at the forefront of discovery in future biomedical research.
Our internationally recognised research excellence is well illustrated by work on the discovery of brain tumour therapies and on novel antibiotics. Brain tumours are the most common and lethal of cancers in young adults and children, making treatment discovery extremely urgent. Treatment development in our Brain Tumour Centre of Excellence requires multiplexed imaging, recording up to 12 different molecules simultaneously in one tumour sample. Our microscopes only allow us to detect 5 molecules. Speed and capacity to determine tumour composition with multiplexing is key for identification and probing the efficacy of treatment options.
The growing resistance against available antibiotics threatens to leave us defenceless against infections, which would make even minor skin cuts potentially lethal. It is therefore pivotal to discover new antibiotics. The microscopes at our facility are not able to detect bacteria. The proposed microscope would allow us to detect up to 12 different bacteria in one sample per day and quickly test the efficacy of new antibiotics, which we are successfully isolating from deep sea sponges among other sources. Finally, the requested confocal microscope will be part of a well-established, supervised and core funded imaging facility, which runs smoothly. All users will be trained and benefit from on-site, on-demand assistance. Together with the planned and paid regular servicing, the machine will be well-cared for and used for decades.
In summary, the pressing need for a new confocal microscope due to capacity and capability limitations of our extant microscopes will guarantee an efficient use of the new machine. The proposed microscope's novel tools and its modular versatile base will enable our research excellence to grow and generate outstanding results.

The Derriford Research Facility (DRF) of the Faculty of Health was opened by the University of Plymouth in 2017. Translational research is core to our interdisciplinary research with internationally recognised excellence in areas such as brain tumour therapy, neurosciences/ neurodegeneration and antibiotic discovery. In the last five years DRF grew significantly and currently 44 staff and associated students use two confocal microscopes stationed at the microscopy core facility, Plymouth Light Microscopy Services (PLiMS). The heavy use of the instruments creates a bottleneck, with 14-17 days waiting times, severely hampering research progress. The proposed confocal will release this bottleneck and speed-up discovery. Critically, we also need to enhance our microscope capabilities to allow us to enter novel avenues and remain at the forefront of biomedical research. Our current confocals are limited to five-wavelength imaging and obsolete photomultiplier tube (PMT) detectors. We thus apply for a modular machine with white light laser (WLL), HyD/ HyX detectors, software enabled resolution enhancement and Fluorescence Lifetime Imaging Microscopy (FLIM). WLLs allow all wave-length excitation, while the new detectors will increase emission detection by 100%. Detectors and WLL will add multiplexing capabilities to PLiMS, enabling superior and faster stratification of and therapeutic development for brain cancers, and kick-start novel research in antibiotic development by bacterial identification via fluorescent in situ hybridisation (FISH). The microscope is also equipped with Fluorescence Lifetime Imaging Microscopy (FLIM) and its reduced photon scattering permits the study of filament interactions, cell signalling and autophagy in thick tissues - essential for advancing research in neurodegeneration. If granted the instrument will be embedded into the well-established structure of PLiMS and is anticipated to last for decades boosting and transforming our research.