Molecular mechanisms of central nervous system regeneration

The aim of the project is to discover and test candidate molecular mechanisms underlying regeneration after central nervous system (CNS) injury using the fruit-fly Drosophila melanogaster as a model organism. The human CNS does not regenerate after injury or disease, but some animals can regenerate their CNS and this generally involves restoring cell populations, natural in vivo cell reprogramming, de novo neurogenesis followed by integration of new neurons into functional neural circuits. We aim to understand how using genetics it may be possible to promote regeneration. The cellular processes underlying structural CNS change include neurogenesis and gliogenesis, cell death and cell loss, changes in cell shape (generation or loss or axons, dendrites, glial projections), synapse formation and loss, leading to neural circuit modification and modification of behaviour. The fruit-fly Drosophila is the most powerful model organism to carry out functional genetic analysis in vivo. The team lead by Prof Alicia Hidalgo pioneered research into injury in the ventral nerve cord of Drosophila, in embryos and larvae and discovered a gene network that regulates the regeneration of glial cell populations after injury. They also discovered a neurogenic conversion of glial cells into neural stem cells upon injury. They have applied the larval contusion method to the adult VNC to investigate regeneration in adult flies. The project will also use molecular biology, laser scanning confocal microscopy and time-lapse imaging, computational image analysis, stimulating neuronal function with opto- and thermos-genetics in vivo, and recording and analysing fruit-fly behaviour. Discovering novel mechanisms of CNS regenerative responses will contribute to understanding fundamental cell biology of the CNS, ultimately with an impact in understanding how to promote regeneration after injury, brain damage or disease also in humans.