An organism's ability to adapt to stress or new environments has major impacts on both its evolutionary success, and its potential to transform into diseased states. Genetically encoded traits—those “written” in the DNA—store selected information that protects against numerous destabilizing forces, experienced over evolutionary timescales. Epigenetic traits, on the other hand, can promote rapid phenotypic change, controlling how the genome is expressed upon stress or novel environmental signals.
The Garcia Lab aims to uncover, in molecular detail, epigenetic traits that influence how cells respond to changing growth conditions or stress. We focus on prion-based forms of RNA-modifying enzymes in budding yeast. Prions are proteins that can fold into stable, alternate structural conformations that become self-templating/heritable, and can alter their functions. RNA-modifying enzymes are evolutionarily conserved enzymes involved in the chemical modification of all RNA species throughout nature. We are interested in how these prion protein conformations form, how their activities on RNA are affected, and how consequent chemical changes to RNA affect which genes are expressed and at what levels. In the long-term, we are interested in taking what we learn in yeast and exploring its conservation in humans, to understand how these epigenetic traits may affect health or influence disease.
Apart from studying models of RNA-modifying enzymes that can act as prions in yeast, we are also investigating more general features of how these enzymes catalyze chemical changes to RNA, and developing direct RNA-sequencing technology to profile a variety of RNA modifications in vivo.