The role of autism-related genes in brain wiring and social behaviour

Project background and description 

Social interactions are fundamental to animals. However, the groups of interconnected neurons—neural circuits—underlying social behaviours are poorly understood in humans, and technologies to identify and study them at the synaptic level do not yet exist.

Our lab therefore uses the larva of the fruit fly, Drosophila melanogaster, an established neuroscience model that engages in complex social behaviour. While foraging for food, individual animals choose between foraging on their own and joining forces in cooperative digging groups [1]. To understand the neural basis of this behaviour, we have mapped the entire brain of the larva, including all neurons and their synaptic connections [2]. We linked this map to genetic tools allowing us to active or inactive individual neurons and determine the effect on behaviour. We identified neural circuits that are required for cooperative behaviour, but how those neural circuits wire together and which genes are involved in this process is unclear.

The proposed project will focus on investigating whether genes associated with autism spectrum disorders (ASD) are important for social behaviours in the fruit fly larva. The fruit fly shares many of the same genes as humans, including ~75% of disease-causing genes. Many ASD-related genes regulate dendrite morphology, synaptogenesis, or neuronal connectivity and could therefore be involved in the development of social circuits. This project will involve mutating ASD-related genes and testing their effect on larval cooperative behaviour using custom behavioural rigs and AI-based animal tracking. This work will open the door to comparative brain mapping in the future to determine how different ASD-related mutations affect brain wiring.

The student will learn a variety of techniques, including fruit fly genetics, behavioural experiments, and python-based data analysis.

Candidate background

The post holder should embody and demonstrate the Crick ethos and ways of working: bold, open and collegial. The candidate must be registered at a UK Higher Education Institution, studying in the UK and must have completed a minimum of two years’ undergraduate study in a relevant discipline, and on track to receive a final degree grade of 2:1 or 1. In addition, they should be able demonstrate the following experience and key competencies:

• This project would suit candidates studying biomedical sciences with a strong interest in experimental work.
• Good knowledge in relevant scientific area(s)
• Good written and spoken communication skills
• Ability to work independently and also capable of interacting within a group

References

1.         Dombrovski, M., Poussard, L., Moalem, K., Kmecova, L., Hogan, N., Schott, E., . . . Condron, B. (2017)

            Cooperative behavior emerges among Drosophila larvae.

            Current Biology 27: 2821-2826 e2822. PubMed abstract

2.         Winding, M., Pedigo, B.D., Barnes, C.L., Patsolic, H.G., Park, Y., Kazimiers, T., . . . Zlatic, M. (2023)

            The connectome of an insect brain.

            Science 379: eadd9330. PubMed abstract