A novel Drosophila platform to replace the use of mice and zebrafish for the study of ER-mitochondria interactions

Why did we fund this project?

This award supports the transfer of the use of a non-invasive Drosophila imaging approach to replace mice and zebrafish in live imaging studies of organelle function and interaction in neuronal ageing.

Dr Alessio Vagnoni previously developed procedures for imaging axonal mitochondrial transport in the sensory neurons of the marginal nerve in the Drosophila wing. Since the wing is translucent and the fly has a short lifespan, axonal transport can be studied in the intact nervous system throughout ageing. During his David Sainsbury Fellowship, Alessio expanded the utility of the fly wing model as a potential replacement for the use of mice by developing new assays to assess interactions between the mitochondria and endoplasmic reticulum, which are often perturbed in neurodegenerative diseases, and to measure intracellular calcium levels following neuronal stimulation. The relatively short lifespan of Drosophila makes longitudinal studies of neuronal ageing more feasible and functional genetic studies can be performed by creating transgenic lines of flies. To validate the replacement potential of the fly model, comparative studies were conducted in the exposed sciatic nerve of ageing MitoMice – transgenic mice in which mitochondrially-targeted fluorescent proteins are selectively expressed in neurons.

Dr Tito Cali at the University of Padova works on mitochondria-ER interactions. With NC3Rs funding, Alessio will work with Tito to transfer the Drosophila model and imaging techniques replacing the use of some experiments using mice and zebrafish in his laboratory.