What’s upstream of loss of nuclear TDP-43 function? -The impact of phosphorylation on RNA binding

The protein TDP-43 is dysfunctional in almost all MND patients, failing to process RNA, and toxically clumping in neurons. This project will elucidate how early protein alterations impact correct RNA binding and processing. We will assess this not only in cultured cells, but also within our unique transparent zebrafish model. This model allows us to look within a living animal to track protein behaviour in single neurons in real time. Uncovering how early changes lead to disease gives us new potential targets for delaying or altering the course of MND.