Research
The accurate and timely production of functional proteins is critically important for cellular activities. Thus, cells have evolved an extensive molecular network to monitor both the quality and quantity of newly synthesized proteins. In particular, the co-translational surveillance of newly synthesized proteins at the ribosome is the earliest point for the cell to assist protein maturation and perform quality control. Our group integrates chemical, biochemical and cell biology approaches to discover and understand the co-translational pathways that regulate the fate of newly synthesized proteins and their associated mRNAs. Such co-translational molecular network is an emerging and under-examined area of research in a wide range of diseases, including infectious diseases, neurodegenerative disorders and cancers.
Quality control at the ribosome
Building a protein is not just about assembling a chain of amino acids in the right order. As a polypeptide emerges from the ribosome, it must begin folding into its precise three-dimensional structure, navigate to the correct cellular compartment, and avoid inappropriate interactions with other molecules. However, errors can arise from genetic mutations, defective mRNAs, or misfolding during synthesis. If left unchecked, these aberrant translation products can accumulate and disrupt cellular homeostasis.
To safeguard the cell, intricate quality control systems monitor nascent proteins as they are being synthesized. These early surveillance pathways detect faulty translation events, prevent harmful interactions, and target defective products for degradation before they can cause damage. Our research focuses on identifying the key molecular players and uncovering the mechanisms that govern these co-translational quality control processes. By understanding how cells maintain protein integrity from the very beginning of synthesis, we aim to reveal fundamental principles of cellular proteostasis and their implications for human disease.
Quantity control at the ribosome
Besides safeguarding the fidelity of protein synthesis, cells must also precisely control how much protein is produced from their transcriptome. A striking example of this quantitative control is tubulin autoregulation—a negative feedback mechanism in which cells selectively reduce tubulin mRNA levels when the pool of soluble tubulin rises. In this pathway, a specialized ribosome-associated factor recognizes nascent tubulin polypeptides as they emerge from actively translating ribosomes. This interaction couples the cellular tubulin state to the translation machinery, triggering targeted degradation of tubulin mRNAs. Our research uses tubulin autoregulation as a model system to uncover how ribosomes integrate regulatory signals to control protein output.
Host factors in viral infection
All viruses depend on host factors to complete multiple stages of their infection cycles, including the translation of viral proteins. A promising antiviral strategy is to target and disrupt host cell factors that are required for viral replication or persistence. An ideal host factor target would be non-essential for normal cellular function, yet even moderate inhibition would significantly impair viral production. Such a host-directed therapeutic (HDT) approach is less prone to the development of resistance caused by viral mutations, as resistance would require the virus to adapt to and exploit alternative host factors for replication. We integrate two latest proteomic techniques, based on in situ proximity labelling and chemical crosslinking methods, to uncover host-virus protein-protein interactions in living cells and provide anti-viral strategies.
