Molecular recognition in post-transcriptional regulation 2

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The functioning of the human body and of complex organisms in general requires different proteins to be produced in different types of cells. This cell-type-specific protein production is achieved by precisely regulating the translation of the genetic code into proteins. The two steps in this process of translation are, first, the translation of the DNA-encoded information into RNA and, then, the translation of the RNA code into a protein molecule. Both processes are regulated by biological machines, which are composed of proteins and, in some cases, RNA molecules. We focus on the regulation of the RNA-to-protein step (or post-transcriptional regulation) and investigate how the protein RNA machines assemble in a solution environment and regulate gene expression. Our structural studies complement other techniques such as X-ray crystallography, which can be used to study molecules in a static crystalline state. Analysing the structures of the molecules that govern regulation of protein synthesis has a direct medical relevance, as this process lies at the basis of common genetic diseases, cancer and viral infections. We work on an important regulatory mechanism, called ARE mediated mRNA decay (AMD), that increase the synthesis of specific proteins in inflammation and healing processes. This mechanism, if permanently switched on, can lead to inflammatory arthritis and cancer. We want to understand how the switch works at the molecular level and design specific therapies to switch in off when required.||Using a similar technical approach we are also investigating a key regulatory protein from herpes virus. This project wants to facilitate the design of anti-herpes drugs to treat people infected with this virus, which forms a major threat to immunodepressed patients, increases the risk of organ transplantation and chemotherapy and reduces the life expectancy of AIDS sufferers. Molecular insight into the interaction of ICP27 with its functional binding partners needs to be obtained if we are, for example, to design or optimise compounds to lock protein and RNA in a non-functional conformation or to (de)stabilise protein RNA complexes.