Sussex Neuroscience

Professor Claudio Alonso

Claudio

From genes to behaviour

Given that all circuit components of behaviour –i.e. sensory neurons, interneurons, motor neurons and their synaptic connections– are constructed under the direction of the genes, mutations affecting the structure or function of any of these components are likely to alter behaviour and offer a window into the molecular processes that underlie brain function at the cellular level. My lab uses a genetic approach to investigate the formation and function of neural circuits. We exploit the simplicity and genetic accessibility of the fruit fly’s brain, where we can identify and study the function of individual neurons in different genetic and physiological conditions. Our use of Drosophila builds on the principle that, at a fundamental level, the processes that build and activate neural circuitry are evolutionarily conserved across all animals, including humans.

This project builds on a discovery recently made in our lab (Picao-Osorio et al. 2015 Science; Issa et al 2019 Current Biology) that mutation of single fruit fly genes can affect a complex behaviour termed self-righting, a motor sequence that is evolutionarily conserved all the way from insects to humans and that allows a subject to return to its normal position if turned upside-down. Using state-of-the-art neural connectomics approaches we have recently mapped the cellular circuitry underlying self-righting opening an opportunity to investigate the impact of genetic changes on the function of an entire circuit.

In this project, will use the self-righting system (and other motor paradigms) to investigate the molecular and physiological mechanisms by which neurons control movement. We will combine modern quantitative behavioural approaches and genetic and optogenetic manipulations of single neurons to establish how genetic information affects the activity of neural circuits. These will involve single-cell transcriptomics, advanced optical imaging, 2-photon microscopy, optogenetics and computational modelling of circuits and behaviour. All in all, the project will take us all the way from the gene to neural function and behaviour and contribute to the understanding of the molecular basis of behaviour.

The Alonso Lab is a competitive and dynamic laboratory generously supported by The Wellcome Trust and the Medical Research Council (MRC). The team is driven by an international group of talented PhD students and post-docs with diverse backgrounds including Molecular Biology, Genetics, Neurobiology, Animal Behaviour and Bioinformatics. The common denominator across all members is our commitment to understand how genes control the formation and function of the brain. If this interests you, you should join us!

For informal enquiries please contact Claudio Alonso: c.alonso@sussex.ac.uk

Key References

(N.B. to see all our papers go to the Alonso lab pages on the School of Life Sciences website)

1. Picao-Osorio, J, Johnston, J., Landgraf, M., Berni, J. and Alonso, C.R. (2015) microRNA encoded behavior in Drosophila, Science 350:815-20

2. Issa, A.R., Picao-Osorio, J., Rito, N., Chiappe, M.E. and Alonso, C.R. (2019) A Single MicroRNA-Hox Gene Module Controls Equivalent Movements in Biomechanically Distinct Forms of Drosophila, Current Biology 29:2665-2675.e4

3. Picao-Osorio J, Lago-Baldaia I, Patraquim P and Alonso, C.R. (2017) Pervasive behavioural effects of microRNA regulation in Drosophila, Genetics 206(3):1535-1548

4. Kaschula R., Pinho, S. and Alonso, C.R. (2018) microRNA-dependent regulation of Hox gene expression sculpts fine-grain morphological patterns in a Drosophila appendage, Development pii: dev.161133. doi: 10.1242/dev.161133 (published online 24 August 2018)

5. Rogulja-Ortmann, A., Picao-Osorio, J., Villava, C., Patraquim, P., Lafuente, E., Aspden, J., Thomsen, S., Technau, G.M. and Alonso, C.R. (2014) The RNA binding protein ELAV/Hu regulates Hox RNA processing, expression and function within the Drosophila nervous system, Development 141:2046-56

6. Mallo, M. and Alonso, C.R. (2013) The regulation of Hox gene expression during animal development, Development 140(19): 3951-63.

7. Alonso, C.R. and Wilkins A.S. (2005) The molecular elements that underlie developmental evolution, Nature Reviews Genetics, 6 (9): 709-715.