BBSRC MIBTP - Understanding nuclear functions of ribosomal proteins in synchronising gene expression during growth.

Gene expression is the process that leads from gene to active protein. The process involves three fundamental steps in eukaryotic organisms such as animals: transcription of DNA into RNA, processing of the primary transcript (pre-mRNA) and then translation of the mRNA into protein. Similar to other complex biochemical processes, the different steps of gene expression are coordinated in the cell. There are two levels of coordination; one involves coupling between the different biochemical reactions, for example, pre-mRNA processing reactions such as splicing of introns are coupled to transcription so that the newly synthesized RNA is still attached to the RNA polymerase while it is spliced; the other level of coordination requires synchronized expression of several genes to produce a given functional output. For example, the cell capacity to synthesize proteins is strictly dependent on the number of ribosomes present, so during growth the number of ribosomes must be doubled before cell division. The ribosome, however, is one of the most complex molecular machines in the cell, composed of about 80 different proteins and 4 RNAs. The building of such a complex machine requires synchronized expression of hundreds of genes. How cells achieve this level of synchronization is not well understood, particularly in multicellular organisms. This research project aims to understand these mechanisms in the fruit fly Drosophila melanogaster which is one of the most amenable model organisms used in many labs throughout the world. We envisage that the results of this research will advance our knowledge of basic cellular processes and, because about 70% of disease associated genes are conserved between Drosophila and humans, lead to a better understanding of human diseases, which, like cancer, are often the result of the failure of mechanisms that coordinate ribosome production with growth.