The brain is plastic: neurons and glia make adjustments in cell size and shape (dendrites, axons), in synapses, and in cell number, throughout life. This structural plasticity is necessary for learning and long-term memory, for the brain to change with experience, and for regeneration and repair. 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 brain diseases are linked to loss of this balance, e.g. brain tumours (e.g. gliomas) or neurodegeneration (eg Alzheimer’s and Parkinson’s disease). Conversely, the homeostatic mechanisms that keep the brain stable also prevent the central nervous system from regenerating upon damage. We want to understand how these forces operate in the brain. Ultimately, this will reveal fundamental principles of how the brain works. Importantly, it will reveal how to help treat brain disease, brain damage and spinal cord injury.
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, in regeneration and repair.
We will use the fruit-fly Drosophila as a model organism, as it is the most powerful genetic model organism. Drosophila genetics has for nearly a century provided ground-breaking discoveries of immense relevance for human health. Drosophila research so far has resulted in five Nobel Prizes, ranging from the discovery of the chromosomal basis of inheritance, to the genetic basis of the body pattern and the universal mechanism of innate immunity. The Drosophila genome was the first complex genome to be sequenced. All the fruit-fly neural circuits are currently being mapped, 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, not in a dish, 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.
To investigate molecular and genetic mechanisms of brain structural plasticity and regeneration in the fruit-fly Drosophila
We will use a combination of genetics, molecular cell biology including CRISPR/Cas9 gene editing technology and transgensis, microscopy, including laser scanning confocal microscopy and calcium imaging of neuronal activity in time-lapse, 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.
Anthoney N, Foldi I and Hidalgo A (2018) Toll and Toll-like receptor signalling in development. Development, 145, dev156018. Doi:10.1242/dev.156018
Kato K, Losada-Perez M, Hidalgo A (2018) The gene network underlying the glial regenerative response to central nervous system injury. Developmental Dynamics DOI 10.1002/dvdy.24565
Hidalgo A and Logan A (2017) Go and stop signals for glial regeneration. Current Opinion in Neurobiology 47, 182-187
Ulian- Benitez S, Bishop S, Foldi I, Wentzell J, Okenwa C, Forero M, Zhu B, Moreira M, Phizacklea M, McIlroy G, Gay NJ, Hidalgo A (2017) Kek-6: a truncated Trk-like receptor for Drosophila Neurotrophin 2 regulates structural synaptic plasticity. PLoS Genetics, 13(8): e1006968.
Foldi I, Anthoney N, Harrison N, Gangloff M, Verstak B, Ponnadai Nallasivan M, AlAhmed S, Phizacklea M, Losada-Perez M, Moreira M, Gay NJ and Hidalgo A (2017) Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila. J Cell Biol 216(5):1421 JCB selected “One of Top 10 articles of 2017”; JCB Selected for special collection on Cellular Neurobiology 2018 as “one of the most exciting findings in cellular neurobiology”.
Losada-Perez, Harrison, Hidalgo (2016) Molecular mechanism of central nervous system repair by the Drosophila NG2 homologue kon-tiki. Journal of Cell Biology 214 (5) 587-601.
McIlroy G, Foldi I, Aurikko J, Wentzell JS, Lim MA, Fenton JC, Gay NJ and Hidalgo A (2013) Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS. Nature Neuroscience 16, 1248-1256
Kato K, Forero MG, Fenton JC and Hidalgo A (2011) The glial regenerative response to central nervous system injury is enabled by Pros-Notch and Pros-NFkB feedback. PLoS Biology 9: e1001133
Zhu, Pennack, McQuilton, Forero, Mizuguchi, Gu, Fenton and Hidalgo (2008) Drosophila neurotrophins reveal a common mechanism of nervous system formation. PLoS Biology 6, e284.
How good is research at University of Birmingham in Biological Sciences?
FTE Category A staff submitted: 42.80
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