IRES

IRES
A typical mammalian cell contains about 10,000,000 ribosomes, each of which can synthesize an average-sized protein within 1–2 minutes. These millions of protein-synthesis assembly lines are controlled by intricate mechanisms to ensure that the right proteins are made at the right place at the right time. Such translational control mechanisms are crucial for a wide range of cellular activities, including homeostasis, development, and memory. Intriguingly, many RNA viruses have evolved RNA sequences called internal ribosome entry sites, or IRES, that can hijack the host translational control system to produce vast amounts of viral proteins. Our goal is to thoroughly understand how these IRESs control the host translation and apply these mechanistic insights to advance mRNA-based therapeutics. We have established a fully reconstituted eukaryotic translation system to study these IRES sequences in vitro. Building upon this core technology, we will explore along two major directions: 1) experimentally study novel IRES candidates that we have computationally predicted from viral metagenomes; and 2) use in vitro selection to evolve new IRES sequences for therapeutic applications.