Carson Thoreen, PhD

The mammalian target of rapamycin (mTOR) pathway is an evolutionarily conserved master regulator of cell growth with important roles in metabolism, aging and cancer. The pathway senses nutrient and growth signals, and responds to these by regulating many major metabolic pathways, but particularly mRNA translation. We found that acute inhibition of mTOR selectively inhibits the translation of large class of mRNAs containing a terminal oligopyrimidine (TOP) motif at the 5’ terminus by disrupting the mRNA cap-binding complex, eIF4F. The mTOR pathway has many additional targets in the translational machinery, but the functional significance of these is unknown. We want to understand how mTOR-regulated translational mechanisms work in molecular detail, what features in mRNAs determine their dependence on mTOR activity, and how these controls are employed physiologically.