Investigating metabolite-RNase communication

Within living cells a whole series of chemical reactions occur in order to provide the energy the cell needs to sustain life. This series of reactions is collectively known as a cell's metabolism. Understanding how metabolism is controlled within a cell is fundamentally important and is directly applicable to medical, environmental and biotechnological advances. At the present time, some aspects of how metabolism is controlled are understood, but we have recently discovered a whole new control mechanism of key importance.

It is already known that messenger molecules (RNA) within a cell play a role in controlling metabolism and that in turn, destroyer molecules (RNA degraders) in the cell keep the number of RNA molecules in check. Our studies have identified that one of the chemicals involved in metabolism, known as a metabolite, interacts with an RNA degrader and affects its ability to destroy RNA. Our work therefore indicates that a full feedback system exists within a cell, with metabolites altering the ability of RNA degraders to destroy RNA, which in turn affects cellular metabolism, which impacts metabolites, which then interact with RNA degraders and so the loop continues.

The aim of the proposed work is to investigate the newly identified interactions between metabolism and RNA-degraders in detail. Specifically, our objectives are to answer a number of key questions. What changes occur to the population of messenger molecules within the cell when this mechanism takes place and are some messenger molecules targeted earlier than others? By monitoring the population of messenger molecules can it be seen whether the mechanism changes once the RNA-degraders form larger complex structures with other RNA degraders? If we specifically change the metabolite-recognition site on the RNA-degrader, what happens to the population of messenger molecules and what can this tell us about the mechanism? Is this mechanism of communication between metabolism and RNA-degraders found in all types of cells from simple bacteria to complex animal cells? To answer these questions our research will use a comprehensive state-of-the-art toolset of proven practical and computational biological research techniques.

Understanding these additional details about the communication between metabolism and RNA-degraders allows us to take the next step towards realising the full impact of our recent discovery. In the longer term, such knowledge could allow scientists to artificially control metabolism within living cells. For example, simple bacterial cells play an important role in many industrial applications and this artificial metabolic control could optimise their use. This may potentially increase efficiency by reducing energy costs, increasing yields and reducing starting material requirements, all of economic and environmental value. Examples include exploitation within the pharmaceutical industry (e.g. more efficient drug production), the food industry (e.g. improvements in food production) and particularly in relation to environmental concerns (e.g. aiding biofuel production and bioremediation projects). In a similar manner, the artificial control of metabolism within animal cells has the potential to offer far reaching therapeutic benefits.