African sleeping sickness is caused by infection with trypanosome s. Infection of domestic livestock causes a range of diseases that restrict the development of small holder agriculture. The WHO estimates that up to half a million people currently suffer from sleeping sickness, which is fatal if untreated. Trypanosomes are single-celled eukaryotes that have several unusual features including the mechanism used to regulate gene expression. Whereas most organisms regulate gene expression by only turning on a gene when it is needed, trypanosomes keep the genes on all the time and degrade the gene product (messenger RNA) that is not required. This is an unusual system of regulation and may be exploitable as a target for therapeutics aimed to force the trypanosome to express the wrong genes. This proposal aims to investigate further how the messenger RNA is degraded by identifying how unstable messenger RNAs are identified in the cell and by characterising the pathway(s) and cellular components necessary for degradation. This work is greatly facilitated by the recently completed genome sequence and will contribute to the interpretation of the genome sequence.