Automated high-resolution microscope platform with robotics to study pharmacodynamics in 3D cell cultures

Cells in an animal are exposed to changes in their environment (biochemical signals, temperature, mechanical forces, light variations...). They have to interpret this information to adapt and respond appropriately. However, cells in an organism do not function in isolation - they are part of a complex three dimensional (3D) environment. The ability to experimentally recreate such environments and visualise individual cells within, and even subcellular organisation in 3D is therefore essential to study biological processes. Imaging technologies are developing fast to study individual cells in a multicellular environment including overtime, and science is progressing at a fast pace. To be able to image a large number of living samples simultaneously, we need fast, automated microscopes, which ensure high-quality images over time without the need for manual user input. We propose to purchase an easy-to-use microscope (Celldiscoverer 7, from Zeiss), which allows:
1) Automated imaging of the biological processes in real-time
2) High-quality imaging of 2D & 3D samples, fixed or living, without the need for specific or complex sample preparation
3) Imaging in physiological conditions (controlled temperature, humidity, CO2, O2).
The Celldiscoverer 7 is a versatile microscope, with multiple capabilities enabling fast imaging of fine structures in 2D and 3D samples. We will install it in the Liverpool Centre for Cell Imaging (CCI), an open-access shared facility with ~100 registered users/year, from academia and industry. The microscope will serve a breadth of science across the MRC remit.

We will install a new high-content imaging widefield & confocal microscope platform (Celldiscoverer 7) in the Liverpool Centre for Cell Imaging (CCI), capable of long term automated fast and gentle imaging of multiple plates, at high-resolution. It will serve a range of projects within the MRC remit from the University of Liverpool. This investment and the proposed projects benefiting from the new instrument, directly address the MRC priority "molecular and cellular medicine". Specifically, research groups will work towards 1) New advanced therapies (Mesenchymal stromal cell therapy; Monitoring of matrix metalloproteinase inhibitors in 3D cultures; Real time monitoring of immune response to long-acting injectables 2.) Experimental medicine (Adverse outcome pathways of Gastrointestinal Toxicity; Drug induced cardiovascular and liver cytotoxicity; in vivo detection of GTPase activity; nuclear dynamics in hypoxia) and 3.) Antimicrobial resistance (screening of novel antimicrobial coatings).
We will build strong foundations by fostering collaboration, generating knowledge transfer and training the next generation of scientists in state-of-the-art microscopy. The CCI is ideally placed to offer an intensive and cost-effective usage of the equipment as it is an open-access facility with prior expertise in advanced fluorescence microscopy and with a strong support team for optimal exploitation of the quantitative data generated.