Structural studies on macromolecular complexes in translational control and ribosome biogenesis

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The ribosome is a large molecular machine central to the survival of all living cells. Genetic information is brought to the ribosome in the form of messenger RNA (mRNA) which is a mobile, molecular copy of a given gene sequence. The ribosome reads the information stored in the mRNA and translates it by synthesising a protein with a specific structure and function. By understanding the structure of a particular protein, we can often gain insights into its function (and malfunction in disease states) in the cell. Producing ribosomes requires a large proportion of a growing cell‘s resources and several genetic diseases are associated with inefficient ribosome production. Ribosome synthesis goes through a number of ordered steps, involving many proteins that ensure synthesis proceeds correctly. My research will examine two related aspects of protein production, firstly how a particular protein recognises certain mRNAs and prevents them from being translated. Interestingly, this protein is also hijacked by hepatitis C virus, which disguises its genes by mimicking cellular mRNA. The virus might use the normal function of this protein to aid its reproduction. Secondly, I will look at proteins involved in producing ribosomes and how they control the final stages of ribosome maturation.