Gene expression control of proteotoxic stress response

RNA-based drugs—including the vaccines that helped end the worst of the pandemic—can trigger unintended side effects, and no one yet knows exactly why. This project will work directly with companies that manufacture these drugs to find out. The problem is urgent. RNA therapeutics are not a distant possibility; they are already in clinics and will soon treat cancer, genetic disorders, and rare diseases. But their side effects—inflammation, organ stress, immune overreaction—limit how widely and safely they can be used. Without understanding the root cause, manufacturers are essentially designing drugs in the dark. The researchers will grow human cells in the lab and test them in mice, systematically tracking how different RNA drug designs trigger a cellular stress response called proteotoxic stress—the buildup of misfolded proteins that can damage or kill cells. By identifying which molecular features cause this stress, they aim to give drug designers a clear set of rules for building safer RNA medicines. If successful, this work will not produce a new drug itself. Instead, it will provide a fundamental understanding of how cells react to RNA-based therapies, allowing companies to engineer out side effects before clinical trials begin. That could accelerate the entire pipeline of personalised RNA medicine.