Grant: Project Grant

The secret to cure human disease is to understand how the cell, the fundamental building block of the human body, functions. We simply cannot fix what we do not understand and the key to understanding cellular behavior is determining how the static information stored within genes is converted into visible effects. Recently my lab has shown that by and large, the amount and type of gene-output, i.e. the amount and type of proteins made, depend on the nature of a certain part of the coding tape dedicated to this synthesis. The coding tape is called RNA and it contains in fact non-coding fragments, or introns, that interrupt the code of protein synthesis. These non-coding fragments need to be removed in order for the tape to work, a process called splicing. Dysregulation of splicing is the hallmark of many human diseases including cancer. Indeed, our work indicates that introns play an important role in improving cell fitness under stress and that variation in splicing patterns promotes the survival of cancer cells. However, we know very little about why introns were first inserted in the coding tape nor do we understand the signaling pathways leading to the removal of a specific intron at a given time. Understanding the function of introns and the mechanisms of normal and alternative splicing represents a key challenge for future biomedical research, the discovery of biomarkers and therapy development. We will draw on our world-leading expertise in RNA biology and yeast genetics to generate the first global assessment of intron function on an organismal scale and annotate factors that modify splicing in human diseases.