Reconstructing the evolution of monoamines as neurotransmitters

The monoamines are one of the most important groups of neurotransmitter molecules. In humans, they are synthesized in the brain, nerve tissue and adrenal glands. These molecules help to regulate processes such as: emotions, memory, blood-flow, appetite, sleep, cognition and many more. The most classic examples of monoamines include serotonin, dopamine and noradrenalin, and they typically act through coupling to a group of receptors known as G-protein coupled receptors (GPCRs). They are the largest group of receptors in animals (including humans) and they are a significant pharmacological target.
Intriguingly, monoamines and the enzymes responsible for their synthesis have been identified not only in different animals but also in plants, fungi and some bacteria. Indicating that the synthesis and occurrence of these neurotransmitter molecules predate the existence of the nervous system and neurons.

To date, it is not clear how and when during animal evolution monoamines acquired their functions in neuronal signalling, and why they became so important for neuronal functions. Thus, the goal of this fellowship is to reconstruct the evolution of monoaminergic signalling in non-bilaterian animals. To achieve this, I will use a wide set of computational and experimental strategies that will allow me to answer very interesting key biological questions such as:

"How, when, and why did the monoamines (present in plants and bacteria) become neurotransmitters in animals?"
"How ancestral is the use of monoamines as neurotransmitters?"
"How did the nervous system evolve"?
"What is the role of monoamines in the evolution of neurons and nervous systems?"

One of the most important groups of animals in which to study evolution are the early-diverging animals known as 'non-bilaterians', which comprise organisms such as sea sponges, jellyfish, corals, and comb-jellies. These animals are believed to have appeared before the emergence of animals belonging to the Bilateria-which include species such as mice, fish, flies, and humans. One of the main characteristics of the non-bilaterians is the lack of a brain or a complex centralised nervous system. In fact, some of them, such as the sponges and placozoans, completely lack a nervous system or neurons. Being an "ancestral" group of animals, the non-bilaterians will allow us to understand the evolution and development of more complex animals.

The aims of this multidisciplinary fellowship align with the BBSRC's future directive of "Advancing the frontiers of bioscience: Understanding of the rules of life" and the strategic priority area "Data driven biology". This research has exciting potential for breaking new ground in fundamental science, and also for practical applications in fields such as:
Ecology and conservation: Most of the known non-bilaterian animals are marine animals. Some of them have extremely important ecological roles, such as the jellyfish and corals (Cnidarians). Coral reefs provide an important ecosystem for marine animals, including valuable marine resources for local communicates and environments. Corals are currently threatened by processes such as bleaching, climate change, storms and invasive species such as the crown-of-thorns starfish (Acanthaster planci). Understanding the processes involved in cellular signalling and cell communication will help to understand and predict their behaviour, reproduction and conservation.
Neurosciences and medicine: Monoamines act through the activation of GPCRs, which are very important pharmacological targets. There are still many human receptors for which no ligands have been identified. Reconstructing the evolution of these receptors including non-bilaterian animals will allow us to better understand how these receptors appeared and evolved in humans animals and potentially identify the ligands that activate them.

Monoamines are an important group of neuromodulators and neurotransmitters that regulate appetite, cognition and behaviour in animals. Monoamines and the enzymes responsible for their synthesis have been identified in animals but also in plants, fungi and bacteria. Thus, the synthetic pathways and occurrence of monoamines predate the evolution of neurons and nervous systems. To date, it is not clear how during animal evolution monoamines acquired their functions in neuronal signalling and why they became so important for neuronal functions. Reconstructing these events is important for understanding the emergence of the nervous system and neurons as specialised cell-types in animal evolution.

The main goal of this proposal is to reconstruct the evolution of monoaminergic signalling in non-bilaterian animals. To achieve this, I aim to carry out large-scale bioinformatic and receptor-ligand screenings, in vivo experimental pharmacology, spatial expression assays, gene-expression and single-cell RNA-sequencing comparisons to identify and characterise monoamine signalling systems in non-bilaterian animals. After having identified monoamine GPCRs in I will focus on the neuron-less animal Trichoplax. By doing so, I will have the opportunity to study the mechanisms by which monoamines directly impact on effector-cells without the intervention of a synaptic nervous system. The objectives covered by this fellowship will fill substantial knowledge gaps about the origin and evolution of the monoaminergic signalling systems. Additionally, the project is expected to deliver the first experimentally characterised monoamine receptors from non-bilaterians. I also aim to clarify how monoamines integrate cellular communication in a neuron-less animal. Ultimately, the data obtained in this project will provide the first insights into the genes and networks responsible for the emergence and evolution of the neuronal cell-types and the role of monoamine signalling in this process