The transcription factor code: defining the role of a developmental transcription factor in the adult brain.

For the human brain to develop and function correctly, each of its 100 billion neurons must follow a specific and pre-programmed code of gene expression. This code is driven by key transcription factors that regulate the expression of numerous proteins, moulding the neurons identity to create its unique shape and electrical behaviour. A fundamental question in neurobiology is how this neuronal identity is maintained in the adult brain. In Drosophila, some elements of the developmental transcription factor code are also necessary to maintain adult neuronal identity, raising the possibility that an adult transcription factor code also exists.

In this project we aim to identify the role of one of these developmental transcription factors in the maintenance of projection neurons in the adult brain, specifically in the motor cortex. Viral vectors expressing knockdown RNAi have been generated and tested in primary neural cultures. Now, we aim to use these vectors to selectively knockdown transcription factor expression in mature cortical projection neurons in vivo. These neurons will be isolated and analyzed by RNA seq to identify molecular pathways regulated by these transcription factors. This work forms part of a larger project that also examines the effects of knockdown on electrophysiological and morphological properties of these neurons.

This project will develop skills in molecular biology, next gen sequencing technologies and analysis, viral vector packaging and mouse neuroanatomy. The ideal candidate will have a strong interest in Neuroscience. They will hold a BSc(Hons) or MSc in molecular neuroscience, genetics or biochemistry. The ideal candidate should express a strong desire to expand their knowledge in particular towards development and application of new tools to manipulate gene expression in living neurons, and be fluent in spoken and written English.