A Holistic View of Gene Expression in Archaea

Archaea — single-celled organisms that look like bacteria but operate more like us — are transcribing their genes and building proteins at the same time, in the same place, without a nucleus to separate the two processes. This project tackles a fundamental gap in biology. Scientists understand gene expression in bacteria and in complex cells (eukaryotes), but archaea sit in between. They use a stripped-down version of the same molecular machinery that humans rely on, yet they couple transcription and translation like bacteria do. No one has mapped how their RNA polymerase and ribosome work together in real time, across the entire genome, or how those machines sense the cell’s metabolic state. If successful, this work will produce the first genome-wide profiles of coupled transcription–translation in a living archaeon, along with structural snapshots of the molecular complexes involved. The impact is primarily on fundamental science: understanding how gene expression evolved, and how a streamlined version of our own machinery handles tasks that in humans require far more components. That knowledge could eventually inform synthetic biology efforts to build minimal expression systems, or help interpret why certain human transcription factors malfunction in disease. But for now, the value lies in filling a blind spot in the tree of life.