Mechanisms of neural circuit evolution: from molecules to networks

A Crick PhD position for the 2021 programme in the lab of Lucia Prieto-Godino.

Project background and description

Our lab is interested in understanding at the genetic and cellular level how neural circuits develop, function and evolve. We address these complex questions through a multidisciplinary approach, using the olfactory system of flies as our main model circuit.

We and others have previously shown that olfactory guided behaviours can evolve through changes in the periphery, at the level of olfactory sensory neurons (Prieto-Godino et al. 2017 Neuron, Prieto-Godino et al. 2016 Nature, Prieto-Godino et al. 2020 Science Advances).  In addition, behavioural diversity can evolve through modification in how sensory information is processed in the brain, but we know much less about how this happens. In the lab we investigate these processes by combining behavioural studies, with two photon imaging, electron-microscopy based connectomics, and single cell transcriptomics. We have found that evolutionary relatives of the lab model D. melanogaster display species-specific behaviours towards odour sources. This is associated with changes their olfactory sensory neuron ensemble representations of the chemical environment. Furthermore, by performing comparative connectomics between D. melanogaster and D. erecta larvae, we found differences in how their central olfactory processing neurons are interconnected, and by using transcriptomics we are investigating the genetic bases of these changes. Addressing these questions often require the development of novel imaging and behavioural set-ups (Zimmermann et al. 2020 bioRxiv, Janiak et al. 2020 bioRxiv, Chagas et al. 2015 PLoS Biology), as well as analysis tools, and can benefit from modelling approaches. This project will investigate the question of how neural circuits evolve by following up on the lab findings.

Another project in the lab investigates how the olfactory system of different tsetse fly species, vectors of sleeping sickness in sub-Saharan Africa, has adapted to blood feeding on diverse animal hosts. In the future this knowledge will be used to create novel vector control strategies. The project combines molecular techniques such as evolutionary analysis of olfactory receptor families and transcriptomics of olfactory organs, with neuroscience approaches, including behaviour, neuroanatomy and physiology in different tsetse fly species.

Other interest of the lab resides on understanding the contribution of neuron-specific read-through to neuronal transcriptomic diversification. 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). This project aims at understanding the generality of this phenomenon, the mechanisms of the tissue-specificity, and its consequences for evolution and diseases.

These are examples of the sort of questions you could ask in this research group. The precise project will be developed with the supervisor and driven by the individual student’s interests and background.

Candidate background

Applicants should be curious about how neural circuits evolve. A background in neuroscience or molecular biology, as well as skills in bioinformatics or computational approaches would be useful, but ample opportunities for training will be provided.

References

1.         Prieto-Godino, L.L., Rytz, R., Cruchet, S., Bargeton, B., Abuin, L., Silbering, A.F., . . . Benton, R. (2017)

            Evolution of acid-sensing olfactory circuits in Drosophilids.

            Neuron 93: 661-676 e666. PubMed abstract

2.         Prieto-Godino, L.L., Rytz, R., Bargeton, B., Abuin, L., Arguello, J.R., Dal Peraro, M. and Benton, R. (2016)

            Olfactory receptor pseudo-pseudogenes.

            Nature 539: 93-97. PubMed abstract

3.         Prieto-Godino, L.L., Silbering, A.F., Khallaf, M.A., Cruchet, S., Bojkowska, K., Pradervand, S., . . . Benton, R. (2020)

            Functional integration of “undead” neurons in the olfactory system.

            Science Advances 6: eaaz7238. PubMed abstract

4.         Zimmermann, M.J.Y., Maia Chagas, A., Bartel, P., Pop, S., Prieto-Godino, L.L. and Baden, T. (2020)

            LED Zappelin’: An open source LED controller for arbitrary spectrum visual stimulation and optogenetics during 2-photon imaging.

            HardwareX 8: e00127.

5.         Janiak, F.K., Bartel, P., Bale, M.R., Yoshimatsu, T., Komulainen, E., Zhou, M., . . . Baden, T. (2019)

            Preprint: Divergent excitation two photon microscopy for 3D random access mesoscale imaging at single cell resolution.

            Available at: BioRxiv. https://www.biorxiv.org/content/biorxiv/early/2019/10/29/821405.full.pdf

6.         Maia Chagas, A., Prieto-Godino, L.L., Arrenberg, A.B. and Baden, T. (2017)

            The €100 lab: A 3D-printable open-source platform for fluorescence microscopy, optogenetics, and accurate temperature control during behaviour of zebrafish, Drosophila, and Caenorhabditis elegans.

            PLOS Biology 15: e2002702. PubMed abstract