Translational responses to stress: a global view

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Our bodies are made of very different types of cells: Skin cells are flat and protect our body, while brain cells have cables that pass messages around. Despite being so different, all our cells carry exactly the same information in their genes. What makes them special is what information they use, that is, which genes they switch on and off.Cells need to respond to changes in their environment (stress) to avoid damage or even death. Stress conditions include high or low temperatures, lack of nutrients or a poor supply of oxygen. Cells react to stress by varying the way in which they use the information from their genes.The information on how to make a cell is stored in the form of a DNA molecule. However, this information cannot be read directly: it first needs to be copied into another molecule called messenger RNA (mRNA), from which it can be 'translated' into a protein. Proteins are the components that directly build the cell and make it function, and it is also proteins that are responsible for protecting the cell from the damage caused by stress.Cells react to stress by switching on 'defence' genes and by switching off the genes that are not needed during the response to stress. The process of turning on and off genes often takes place at the level of the translation of messenger RNAs (that is, by selecting which messenger RNAs will be translated into proteins). Studying translation is relevant for human cells, because the mechanisms that regulate translation often go awry during cancer and several inherited conditions.Our aim is to understand how cells change the information they use - especially through translation - to cope with situations of stress. A recently-developed experimental technique allows the simultaneous detection of the translation of every messenger RNA in the cell, thus providing unprecedented insight into how cells regulate translation. The method is called 'ribosome-profiling' after the ribosome, which is the cellular machine that carries out translation. We will apply this approach to study how cells modify translation of messenger RNAs in response to several stress conditions.One way to study a complicated process of the human body is to use a model organism: this is a simpler creature, but similar enough to allow us to learn about ourselves. To study these questions we will employ a simple yeast -made of a single cell- that can react to many different types of stress. We will investigate how the yeast cells regulate translation in response to stress: which mechanisms they use, which genes are turned on an off, and what is the importance of these genes. We expect this information will be useful to understand how human cells behave and, eventually, help us devise cures for disease.