In this groundbreaking episode, we are joined by Dr. Kirkland, a leading expert in the field of biomedical imaging, who guides us through his trailblazing research on bioluminescence imaging (BLI) in the central nervous system. While BLI has become an indispensable technique in biomedical research, allowing non-invasive visualization of cells and biochemical events in vivo, its application in the brain has been a challenge due to the relatively poor performance of luciferases with existing substrates.

Dr. Kirkland discusses his recent discovery of a NanoLuc substrate, cephalofurimazine (CFz), which significantly improves the performance of BLI in the brain. When paired with Antares luciferase, CFz produces over 20-fold more signal from the brain compared to the standard pairing of D-luciferin with firefly luciferase. This leap forward in sensitivity opens up exciting new possibilities for the application of NanoLuc-based indicators in brain research.

We delve into the application of CFz in practical scenarios, including the achievement of video-rate non-invasive imaging of Antares in the brains of freely moving mice and the demonstration of non-invasive calcium imaging of sensory-evoked activity in genetically defined neurons.

With Dr. Kirkland's insights at the forefront, this episode shines a light on the future of neuroimaging, offering listeners a look at the cutting-edge advancements that are enhancing our understanding of brain activity.

Dr. Kirkland, Bioluminescence Imaging, BLI, Central Nervous System, Luciferases, NanoLuc Substrate, Cephalofurimazine, CFz, Antares Luciferase, D-Luciferin, Firefly Luciferase, Brain Research, Non-Invasive Imaging, Calcium Imaging, Neurons.

Su, Y., Walker, J.R., Hall, M.P. et al. An optimized bioluminescent substrate for non-invasive imaging in the brain. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01265-x