The goal of the lab is to understand how evolution sculpts nervous systems, giving rise to novel behaviours. Studying the evolutionary forces imposed on neural circuits can provide us with important insights on how brains work and what goes wrong in diseases. We study these questions using as a model the olfactory systems of several fly species, some of which are pests or contribute to the spread of diseases.

We have a multidisciplinary approach, combining a variety of methodologies including field-work, bioinformatics, electrophysiology, imaging, behavioural analysis, and genetic manipulations. These are some of the projects we are currently doing in the lab.

Evolution of sensory coding

Sensory systems have evolved to optimally process information, however, it is an open question to which extent this optimisation takes place across the sensory systems of closely related species adapted to environments with different stimulus statistics. We address this question by combining fieldwork, enviroment volatile analyses, behavioural studies, and functional imaging from the entire repertoire of olfactory sensory neurons across species.

 

Evolution of central neural circuits

Sensory evoked behaviours can evolve through changes in the periphery, at the level of sensory neurons, or via modification of the way sensory information is processed in the brain by central neural circuits. There is increasing understanding of how receptors and sensory neurons evolve across different species. However, we know little about how central neural circuits are re-shaped during evolution. We are investigating this question using as models the adult and larval olfactory circuits of different Drosophila species with divergent behaviors. We employ a combination of techniques, including:

– Synaptic resolution reconstruction of neural circuits across species. In collaboration with the Cardona and Zlatic labs we are acquiring electron microscopy volumens of the full brain of several larval Drosophila species, and we are tracing their olfactory circuits to identify conserved and divergent elements.

 

– Whole brain calcium imaging. We are combining the development of genetic tools accross Drosophila species and new two-photon microscope imaging methods to image how olfactory information is diferentially processed in brain of  species with divergent odour-guided behaviours.

– High-resolution behavioural tracking in real and simulated enviroments.

 

Function, mechanisms and evolution of neuron-specific read-through

We previously found that some pseudogenes containing premature stop codons, and thus supposedly non-functional, are expressed and function thanks to neuron-specific read-through of their stop codon (Prieto-Godino et al. 2016 Nature).We are interested in understanding  the potential function of neuronally regulated stop codon read-through in the generation of alternative neuron-specific protein functions,  the mechanisms of this tissue-specific read-through, and its consequences for evolution and diseases. We address these questions by combining the power of Drosophila genetics with human induced pluripotent stem cells and advanced sequencing technologies, in collaboration with the Patani and Ule labs at the Crick.

 

Evolution of olfactory receptors in tsetse flies

Tsetse flies (Glossina sp.) are the sole vector for African trypanosomasis, which causes sleeping sickness in humans and nagana in cattle – both of which constitute an important burden particularly in rural areas of Africa. Different tsetse fly species have different host preferences, and the genomes of five of these have recently been sequenced (Macharia et al. 2016 PLoS Negl Trop Dis). We are investigating how the olfactory receptors of tsetse flies detect hosts odours and how they have evolved in different species.

Ecology and evolution of olfactory systems under fluctuating selection

How selection shapes olfactory circuits is still poorly understood. An ideal place to look into this question is across populations subjected to recent and ongoing selection. We are studying this question in populations of D. erecta, a West African fly species that feeds on a host with seasonal availability that imposes fluctuating selection.