Down’s syndrome: understanding the molecular and neurophysiological bases of changes in the brain

Down’s syndrome occurs in ~1 in 700 - 1000 live births. It is caused by the presence of a third copy of human chromosome 21 (trisomy 21; OMIM ID: 190685), which results in altered expression of genes on human chromosome 21 and on other chromosomes. Brain size is reduced and there is a decrease in neuron number and distorted neuronal morphology. These changes are more pronounced in certain regions of the brain, such as the cerebellum and hippocampus. People with Down’s syndrome show impaired learning and memory, poor fine motor skills, altered balance and unclear speech. How information processing in the brain is affected to cause these cognitive and motor deficits is not understood.

The aim of this project is to pioneer the use of Drosophila as a model system in which to study the molecular, synaptic and neurophysiological bases of changes in brain function in Down’s syndrome. It will take advantage of the amenability of Drosophila to genetic manipulation and molecular, electrophysiological and behavioural analyses. The effects of increased expression of individual human genes or sets of human genes that are present in three copies in Down’s syndrome will be explored.

You will receive training in molecular genetics, quantitative PCR, patch-clamp recording, and analysis of synaptic transmission and intrinsic electrical properties. You will learn to use confocal microscopy to quantify changes in neuronal morphology and brain structure, and will develop locomotor and learning assays to help model aspects of the behavioural changes associated with Down’s syndrome. Lastly, you will employ exciting new optogenic techniques to image neural activity, live in circuits controlling locomotion and memory formation. Therefore, you will gain expertise in a range of techniques that enable research from the genome to the whole organism, helping address important medical questions.