Proteins are synthesized by ribosomes that translate information encoded in messenger RNA (mRNA) to proteins. Nascent proteins on the ribosome can have different fates; 1) targeted to different organelles (i.e., ER, Mitochondria), 2) start to fold into structures necessary for their function, 3) assemble into complexes. These processes are mediated by many factors (chaperones) to ensure proper maturation of nascent proteins.
Ribosomes move through mRNA like cars on the roads. There are traffic lights and stop signs controlled by various factors. Moreover, stopping abruptly can also cause ‘accidents’ where ribosomes collide. Interestingly, as organisms age, we find that traffic lights malfunction and stop signs fade, leading to more ‘accidents’ (ribosome collisions). These abnormal ribosome collisions, directly and indirectly, disrupt protein homeostasis to cause and accelerate aging phenotypes. This highlights the importance of ‘regulated’ translation speed (ribosome movement) during the biogenesis of proteins.
Our lab is broadly interested in understanding how the speed of ribosome translation impacts protein synthesis and maturation during different cotranslational events. One of our main experimental approaches is ribosome profiling (Ribo-seq), which allows us to obtain high-resolution information on the movement of ribosomes along the mRNAs. Our goal is to discover novel mechanisms that regulate protein biogenesis and maturation through bioinformatic analysis of sequencing data coupled with biochemical/biophysical approaches.