From Code to Protein: Translational Regulation and Quality Control

The Question

Cells don’t just “make proteins”. They translate genetic information into proteomes that are tuned to cell identity, developmental stage, and environmental conditions. This requires tight control of translational output and fidelity in the face of changing demands. We aim to define the principles that keep translation robust under these shifting conditions.

We focus on three connected questions: how gene expression machines are assembled into functional systems; how translational disturbances are sensed and contained; and how defective or surplus components are removed to maintain homeostasis. A central theme is context dependence: why the same perturbation is buffered in some cell states, but leads to marked proteostasis defects in others.

The Approach

We study defined human cell states and analyse what happens when translation is pushed off balance. We use hiPSCs and differentiated lineages to compare translational regulation and quality control across contexts. Using scalable genetic perturbations and quantitative readouts, we track how cells reshape translation output, engage quality control pathways, and recover proteome integrity or undergo proteostasis collapse. Key findings are followed up mechanistically with targeted genetics and biochemical experiments to connect phenotypes to underlying molecular events.