The transcriptional basis of psychostimulant-induced Parkinsonism

Project Description

Psychostimulant drugs are usually prescribed to treat ADHD and narcolepsy, or consumed as recreational euphoriants. They target the transport of dopamine, a neurotransmitter essential for learning, motivation, sleep, and motor control. Chronic exposure to these drugs can dramatically alter the structure and function of dopaminergic circuits, therefore increasing the risk of developing symptoms of Parkinsonism. A better knowledge of the mechanisms by which psychostimulants disrupt dopaminergic signalling may inform strategies to prevent or alleviate their long-term consequences on brain function.

The goal of this MRes project is to establish the simple brain of the fruit fly, Drosophila melanogaster, as a new model to investigate how psychostimulants undermine the function of dopaminergic neurons. Anatomy and single-cell transcriptomics studies have identified individual clusters of dopaminergic neurons in the fly brain, each with their own connectivity and genetic profile. Powerful genetic tools to manipulate neuronal function in vivo have helped decipher how individual clusters modulate distinct behaviours. This unparalleled knowledge provides a unique opportunity to understand the molecular and cellular impact of psychostimulants on the brain, with a resolution impossible to achieve in other organisms.

The student will establish how chronic consumption of psychostimulants affects dopamine-driven behaviours, with a particular focus on sleep, locomotion and memory. They will also perform 3D reconstruction of dopaminergic neuron anatomy and image registration to quantify potential morphological defects due to drug exposure. Based on this information, they will design and perform an RNA-seq experiment to measure how psychostimulants affects gene expression in dopaminergic neurons isolated with FACS. This experiment will help distinguish idiosyncratic molecular consequences of Parkinsonism from those also triggered by chronic drug consumption, and identify new candidate targets for functional studies investigating the relationships between drug abuse and Parkinsonism.

The work will take place in the group of Dr Vincent Croset in the Department of Biosciences at Durham University. The successful applicant will have the opportunity to work in a dynamic scientific environment and learn essential skills to prepare them for a career in research. They can expect to learn about the physiology of drug abuse and neurodegeneration, behaviour, brain anatomy and histology, genetics, molecular biology, and transcriptomics, including the associated computational aspects. Moreover, they will acquire transferrable soft skills in oral and written scientific communication, critical scientific thinking, and good laboratory practice, including organisation, planning and the ethics of science. Some experience in neurobiology, Drosophila or transcriptomics would be a plus, but curiosity and motivation are more important.

How to Apply

If you are interested in applying for this project, in the first instance contact the supervisor, Dr Vincent Croset, with a CV and covering letter, detailing your reasons for applying for the project.