C2D2 establishment 4a - Evaluating how phosphorylation alters the structure/function relationship of the microRNA biogenesis protein TRBP

The growth, function and death of human cells needs to be tightly controlled. Key to this are the mechanisms for accessing and utilizing the information stored in our genomes. Malfunctions in regulatory mechanisms can mean that information is no longer or incorrectly accessed. One recently identified cellular regulatory system involves small molecules of RNA, a chemical relative of DNA. A large array of regulatory RNA molecules - termed microRNAs due to their small sizes – has been identified including many that are implicated in cancers. Cells produce the majority of these microRNAs via the same manufacturing process. The research outlined here aims to characterize the mechanisms by which cells produce small RNA regulators. A comprehensive understanding of a biological process, or how a disease affects it, requires knowledge at every biological level, from physiology to biochemistry to molecules and atoms. Here we aim to characterise the production of microRNAss at the molecular level, to combine these data with information about modifications to the production machinery, and to relate atomic level understanding to observations at the cellular level. Why is this level of understanding important? Because such information shapes our fundamental understanding of cell function and the process of disease, and because it drives the design of molecular therapies.