Project highlights

  • Nervous system
  • Phylogeny
  • Metazoa
  • Monoamines.

Overview

While it is well established that the Cambrian explosion required a radical change in animal behaviour (e.g. predator-prey arms races), the innovation of the nervous system associated with the diversification of the animals are poorly understood.

Recently we discovered (Goulty et al., 2022) that the genes animals use the monoamine neurotransmitter (a small group of neuromodulators that controls for example, aggression and memory) originated in the bilaterian stem group, pre-dating the Cambrian explosion. This pattern of gene duplication, combined with their role in modulating behaviours, led us to speculate that the evolution of monoamines was one of the key bilaterian innovations associated with the Cambrian explosion. However, in the absence of molecular and functional data, it is not possible to rule out that non-bilaterians use alternative metabolic pathways to synthetize monoamines (e.g. Yu et al., 2022) or from the microbiota (Liu et al., 2020). This project aims to test the presence of monoamines in non-bilaterian animals using a combination of chemistry, evolutionary biology, and genomics. To this aim we have defined three objectives:

  1. To test the presence of monoamines in non-bilaterian metazoans, you will use mass spectrometry.
  2. To study the effect of monoamines on non-bilaterians behaviour.
  3. To identify the putative monoaminergic neurons, you will study the co-expression of the monoamines pathway genes (see Goulty et al., 2022) by combing single-cell RNA-sequencing data and in-situ hybridisation.

This project uses a multidisciplinary approach and recently developed technologies (e.g., single-cell biology) and the field of molecular paleobiology to provide insight into key events in the diversification of animals. Importantly it relies upon model systems and protocols already established in my laboratory.

Figure shows a origin of monoaminergic genes and the presence of neurons over time - Neoprotozeric and Paleozic
Click to enlarge

Figure 1. A simplified time-calibrated species tree illustrating the origin of the key monoaminergic genes and the presence of neurons. A = Sturtian glaciation; B = Marinoan glaciation; C = Gaskiers glaciation; D = Occurrence of Ediacaran Biota/early animal fossils; and E = the Cambrian explosion (from Goulty et al., 2022)

 

Host

University of Leicester

Theme

  • Organisms and Ecosystems

Supervisors

Project investigator

Dr. Roberto Feuda, University of Leicester ([email protected])

Co-investigators

How to apply

Methodology

First, you will perform mass spectrometry on several non-bilaterians metazoans (sponges, placozoans, ctenophores and cnidarians) to evaluate the presence of monoamines. This will be complemented with a phylogenetic analysis of alternative monoaminergic enzymatic pathways (e.g. Yu et al., 2022).

Second, you will test whether the different non-bilaterian animals respond to the different monoamines. You will module the level of the monoamine and record the effect on behaviour using video recording (e.g. DeepCutLab Mathis and Mathis, 2020).

Finally, you will capitalize on existing single-cell RNA-seq data from different animals’ (Sebé-Pedrós, Saudemont, et al., 2018; Chari et al., 2021; as well as new dataset generated in the lab) phyla to identify neuronal diversity in the different groups and use whole-mount in situ hybridization to validate the neuronal diversity in carefully selected taxa.

In summary, this project will equip the candidate with a unique combination of cutting-edge expertise in experimental and computational biology, and the data analyses can be transferred to large, diverse sets of biological problems.

Training and skills

Students will be awarded CENTA2 Training Credits (CTCs) for participation in CENTA2-provided and ‘free choice’ external training. One CTC equates to 1⁄2 day session and students must accrue 100 CTCs across the three years of their PhD.

You will be trained in molecular biology, genomics and phylogenetic methods.

The PhD student will join a large and successful Neurogenetics research grouping that includes 8 PIs, 14 PhDs students and 9 PDRAs working on different aspects of neurobiology (from electrophysiology and molecular neurogenetics to computational genomics). This position offers ample opportunity for training and collaboration with the U.K. and European laboratories. Finally, this project will also provide the opportunity to publish in international 4-star general journals, which are regularly generated by the Neurogenetics group.

Partners and collaboration

Dr. Roberto Feuda and Prof Ezio Rosato of Unversity of Leicester partnering with Dr Vengamanaidu Modepalli of Marine Biological Association UK and Prof. Simon G. Sprecher of University of Fribourg, Switzerland.

Further details

Please contact Roberto Feuda: [email protected] for further information or to discuss the project in more detail.

If you wish to apply to the project, applications should include:

  • A CV with the names of at least two referees (preferably three and who can comment on your academic abilities)

Applications to be received by the end of the day on Wednesday 11th January 2023.

Possible timeline

Year 1

Mass spectrometry.

 

Year 2

Perturbation of the monoamine system.

Year 3

In situ hybridization.

Further reading

  • Chari, T., Weissbourd, B., Gehring, J., Ferraioli, A., Leclère, L., Herl, M., Gao, F., Chevalier, S., Copley, R.R., Houliston, E., Anderson, D.J. and Pachter, L. 2021. Whole-animal multiplexed single-cell RNA-seq reveals transcriptional shifts across Clytia medusa cell types. Science Advances. 7(48), p.eabh1683.
  • Goulty, M., Botton-Amiot, G., Rosato, E., Sprecher, S. and Feuda, R. 2022. Neuromodulation by Monoamines is a Bilaterian Innovation. , 2022.08.01.501419.
  • Liu, Y., Hou, Y., Wang, G., Zheng, X. and Hao, H. 2020. Gut Microbial Metabolites of Aromatic Amino Acids as Signals in Host–Microbe Interplay. Trends in Endocrinology & Metabolism. 31(11), pp.818–834.
  • Mathis, M.W. and Mathis, A. 2020. Deep learning tools for the measurement of animal behavior in neuroscience. Current Opinion in Neurobiology. 60, pp.1–11.
  • Sebé-Pedrós, A., Chomsky, E., Pang, K., Lara-Astiaso, D., Gaiti, F., Mukamel, Z., Amit, I., Hejnol, A., Degnan, B.M. and Tanay, A. 2018. Early metazoan cell type diversity and the evolution of multicellular gene regulation. Nature Ecology & Evolution. 2(7), pp.1176–1188.
  • Sebé-Pedrós, A., Saudemont, B., Chomsky, E., Plessier, F., Mailhé, M.-P., Renno, J., Loe-Mie, Y., Lifshitz, A., Mukamel, Z., Schmutz, S., Novault, S., Steinmetz, P.R.H., Spitz, F., Tanay, A. and Marlow, H. 2018. Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq. Cell. 173(6), pp.1520-1534.e20.
  • Yu, J., Vogt, M.C., Fox, B.W., Wrobel, C.J.J., Fajardo Palomino, D., Curtis, B.J., Zhang, B., Le, H.H., Tauffenberger, A., Hobert, O. and Schroeder, F.C. 2022. Parallel pathways for serotonin biosynthesis and metabolism in C. elegans. Nature Chemical Biology., pp.1–10.

COVID-19

This work has a strong computational aspect (e.g. analysis of existing single-cell RNA-seq data and phylogenetic inference) that does not require access to the laboratory and can be performed from home. The experimental part is expected in the second year, it is flexible, and it can be reduced without affecting the outcome of the project.