Research Theme within School of Biosciences: Structural and Molecular Cell Biology
Lab website address: www.biosciences-labs.bham.ac.uk/hidalgo/
Birmingham Fly Facility: https://www.birmingham.ac.uk/research/birmingham-fly-facility/birmingham-fly-facility.aspx
Nervous system development: structural and developmental plasticity
Our lab aims to understand how the nervous system is formed, and how it works. Structure and function come together in the course of development, and influence each other throughout life, endowing the nervous system with plasticity. As the animal grows and nervous system volume and cell number increase, the two cell types in the nervous system - neurons and glial cells - make adjustments that modify migration patterns, axonal trajectories, cell division and cell survival. These plastic adjustments result in the robust, reproducible formation of the nervous system across individuals, and over evolutionary time. Conversely, these cell interactions fail in diseases of the nervous system and brain (e.g. neurodegenerative diseases, psychiatric disorders and brain tumours) and upon injury (e.g. upon spinal cord injury and stroke).
We use the fruit-fly Drosophila because it is a very powerful model organism to address questions swiftly, in vivo and with single cell resolution. Our approach combines genetics, molecular biology, cell culture, computational analysis and in vivo confocal microscopy in fixed specimens and in time-lapse.
We collaborate with biochemists (Prof. N.J. Gay, Cambridge), electrophysiologists (Dr I. Robinson, Plymouth) and experts using mice and rats as model organisms (Prof. A. Logan, IBR Birmingham and Dr F. Matsuzaki, Riken, Japan).
We have recently discovered:
1. Drosophila Neurotrophins (DNTs):
That a neurotrophin protein family in Drosophila formed of DNT1, DNT2 and Spz regulate neuronal cell number, connectivity and synaptogenesis. This demonstrated conserved structure and function of the neurotrophin super-family from flies to humans. The findings support the notion that a common mechanism underlies the origin and function of all brains in evolution and that there are fundamental aspects in the way brain structure and function are linked, in fruit-flies and humans. These findings are important to use Drosophila as a model to understand the brain and to model brain diseases.
2. DNT receptors of the Toll superfamily
That the receptors for the DNTs belong to the Toll receptor super-family. Whereas Toll receptors have universal functions in innate immunity, we found that Toll-6 and Toll-7 in flies function as neurotrophin receptors to regulate neuronal number and targeting, and hebaviour. This reveals the distinct evolution of neurotrophin signalling, shared origins of the immune and nervous systems, and unforeseen relationships between the neurotrophin and Toll protein superfamilies.
3. A gene network for CNS repair in Drosophila.
We have a discovered a gene network that can promote injury repair in the CNS of Drosophila. We have established a novel paradigm to investigate central nervous system regeneration and repair in fruit-flies. We have shown that we can manipulate this gene network to prevent or promote injury repair. We are collaborating with mammalian experts to directly test whether this gene network also operates in mammalian glia using mice - closer to human conditions.
4. Research in Imaging.
To address questions on structural plasticity, it is essential to acquire quantitative information on cell number (e.g. the number of dying or dividing cells, neurons or glia, in different genotypes or conditions) and number of synapses. Thus we developed programmes to enable us to do exactly that, for the whole central nervous system of Drosophila embryos, larvae and the adult brain. We also developed a programme to track crawling larvae. All of our programmes were developed as ImageJ plug-ins and are freely available through our lab web-page.
Research by the Hidalgo group is funded by: The Wellcome Trust, BBRSC project grants and EU Marie Curie IntraEuropean and International Incoming Fellowship and The Royal Society, and in the past has also received funding from the MRC and EMBO and PhD studentships from the BBSRC, MRC and the Government of Brunei.