From genes to movement: the role of microRNA regulation during the development of motor circuitry in flies and fish - Dual-PhD program between Sussex and HKUST

Summary.
We are looking for an ambitious student interested in participating in a joint PhD project between the University of Sussex (UoS; Alonso laboratory) and the Hong Kong University of Science and Technology (HKUST; Miller laboratory) to investigate the molecular mechanisms that underlie the origins of movement in two modern genetically-tractable systems, Drosophila and zebrafish. The project will combine the use of modern genetics, CRISPR-gene editing, RNA analysis, advanced microscopy, optogenetics and neural activity analyses to study the emergence and development of movement in Drosophila and zebrafish focusing on the roles played by small non-coding RNAs (microRNAs) in this critical biological process. The student will benefit from the international stature and complementary strengths of the Alonso Lab in Drosophila Genetics, RNA biology, Neural Development and Behaviour, and the Miller Lab in Zebrafish Genetics, Embryonic Development and Neural Physiology analysis. We aim to develop an ambitious and exciting research plan to compare and contrast the genetics underlying the development of movement in vertebrates and invertebrates using two key animal systems in modern molecular and developmental biology.

Scientific background.
The cellular components underlying behaviour are in one way or another affected by the activity of genes. Through meticulous analysis of individual gene mutations and their effects on behaviour, it became possible to identify several genes linked to specific behavioural programs. Indeed, recent work in the Alonso Lab showed that mutation of a single Drosophila microRNA affects a specific movement [Picao-Osorio et al (2015) Science 350:815-20]. Furthermore, a recent genetic screen carried out by the Alonso group revealed that ≥40% of all microRNAs expressed in early Drosophila have roles in movement control demonstrating an unprecedented role of microRNA regulation in the control of locomotor behaviour [Picao-Osorio, Baldaia et al (2017) Genetics]. microRNAs are small non-coding RNAs that repress gene activity and as such may represent a key genetic component in the coordination of multicellular processes such as those underlying motor control. Interestingly, several of these ‘motor-miRNAs’ are evolutionarily conserved between Drosophila and zebrafish and are actively expressed during zebrafish early development suggesting that they may play similar roles in the development of movement in the fish.

Biological question and approach.
The project emerges from an exciting collaboration between two international laboratories, the Alonso Lab at Sussex (UK) and the Miller Lab in Hong Kong (China). The project will involve experiments in Drosophila and zebrafish aiming at discovering the genetic basis of movement control in vertebrates and invertebrates. We will use a range of genetic and CRISPR-based gene editing approaches to test the roles of non-coding RNAs in the development of behaviour and investigate the molecular, cellular, developmental and neuro-physiological bases of the effects of RNA control on the development of movement in flies and fish. The work is expected to contribute to the understanding of the molecular basis of movement and provide insights into how this fundamental process operates in health and disease.

For informal enquiries please contact Claudio Alonso at [Email Address Removed]