Structural Brain Plasticity & Degeneration in Drosophila
The brain is plastic: neurons and glia make adjustments in cell size and shape (dendrites, axons), in synapses, and in cell number, throughout life. Such structural plasticity enables the brain to change with experience. But counteracting mechanisms constrain the brain’s ability to change in order to stabilise circuits. The healthy brain is kept in balance between plasticity and homeostasis, resulting in normal behaviour. Exercise and learning increase plasticity, whilst aging and brain diseases (from neurodegenerative like Alzheimer’s and Parkinson’s disease to psychiatric) are linked to loss of this balance towards circuit degeneration. We want to understand how these forces operate in the brain. Ultimately, this will reveal fundamental principles of how the brain works. Importantly, understanding this at a fundamental and mechanistic level will reveal how to help find therapeutic solutions to brain disease.
We tackle this big question by aiming to discover underlying genetic mechanisms, and investigate the interaction between gene networks, cell biology, neuronal activity and behaviour - in the healthy brain, throughout the life-course, in aging and upon genetic manipulation.
We will use the fruit-fly Drosophilaas a model organism, as it is the most powerful genetic model organism. Drosophila genetics has for over a century provided ground-breaking discoveries of immense relevance for human health. Drosophila research so far has resulted in six Nobel Prizes, ranging from the discovery of the chromosomal basis of inheritance, to the universal mechanism of innate immunity and the biological clocks. The Drosophila genome was the first complex genome to be sequenced; all the neural circuits have virtually been mapped in the fruit-fly brain, way ahead of the mapping of human circuits. There are cutting edge genetic and molecular (e.g. CRISPR/Cas9 gene editing) tools to visualise and manipulate neurons and glia, neural circuits, genes, neuronal activity, in vivo and visualise how this changes behaviour. It is an extremely exciting time to investigate neuroscience with the fruit-fly Drosophila, to discover fundamental principles about the brain, including the human brain.
We will use a combination of genetics, molecular cell biology including CRISPR/Cas9 gene editing technology and transgenesis, microscopy, including laser scanning confocal microscopy and calcium imaging of neuronal activity in time-lapse and 2-photon imaging, computational imaging approaches for analysis of images and movies, stimulating and inhibiting neuronal function in vivo, and recording and analysing fruit-fly behaviour.
Ultimately, the findings from our research will have implications beyond Drosophila, with an impact also in understanding how any brain works, in health, injury or disease, including the human brain.
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