Grant: Operating Grant

In cancer, proper gene regulation is lost. 'RNA silencing' is a fundamental process of gene regulation that affects a wide array of cellular functions including cell growth, conversion to different cell types and cell death. Here, short length RNA molecules called small RNAs combine with members of the Argonaute family of proteins, and together target specific messenger RNAs (encoding for proteins), resulting in a lowering of the amount of that protein present in the cell, hence the term 'silencing'. Research into RNA silencing has exploded in recent years and much has been learned about how this process works at the cellular level. This has led to the development of powerful tools for manipulating cellular protein levels and studying gene regulation by way of laboratory synthesized small RNAs, called small interfering RNAs (siRNAs). siRNAs can also be used in a therapeutic manner to manipulate the levels of proteins associated with cancer and other diseases. However, the mechanisms that underlie RNA silencing at the molecular level in humans are at present poorly understood. This proposal aims to use structural biology to unravel the molecular basis of RNA silencing in humans. These studies will substantially progress our understanding of this fundamental mechanism of gene regulation, improve the use of existing tools for studying gene function (i.e. siRNAs), and potentially lead to the development of new siRNA-based drugs against cancer causing genes, which can have a great impact on human health.