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Welcome to Dr. Qian's laboratory
Mysteries of protein folding


Last Update:
Dec 5, 2012


How does the presence of nutrients lead to protein synthesis? How is mRNA translation controlled by nutrient signaling?  How does protein folding and degradation occur during protein synthesis?  How do cells get rid of misfolded proteins?  These are a few of the problems we would like to understand.  Elucidation of the molecular mechanisms underlying protein quality and quantity control will ultimately define new therapeutic strategies to human diseases such as cancer, diabetes, and neurodegenerative disorders.   

Research Projects

    Translational Control in Gene Expression

In eukaryotic cells, a single gene can generate different types of mRNAs by alternative splicing.  A single mRNA can also produce different protein products through alternative translation.  A major challenge in biology is to understand how protein synthesis is regulated with exquisite temporal and spatial precision.

We developed an approach called global translation initiation sequencing (GTI-seq) that enables precise mapping of translation initiation sites (TIS) across the entire transcriptome.  This allows for a comprehensive cataloguing of novel open reading frames (ORFs), which not only contribute to proteome diversity and complexity, but add a new layer of translational regulation mechanisms.

    Nutrient Signaling in Growth and Aging

Mammalian target of rapamycin (mTOR) is a central regulator of cell growth by integrating signals from nutrients, growth factors and energy status.  The rapamycin-sensitive mTORC1 plays a critical role in controlling protein synthesis through a poorly understood mechanism.  Dysregulation of mTORC1 signaling has been implicated in several age-associated diseases, such as cancer and metabolic disorders.

We discovered that mTORC1 signaling not only controls protein quantity, but also influences protein quality as well. We are addressing the critical role of nutrient signaling in growth and aging by focusing on mRNA translation. In addition, we are investigating other cellular pathways, such as autophagy, in response to nutrients starvation.

    Ribosome Dynamics in Co-translational Events

The translation machinery ribosome is a large ribonucleoprotein complex composed of two subunits that associate upon the initiation of translation. The small subunit decodes mRNA and the large subunit catalyzes peptide bond formation. In spite of its fundamental role in protein biosynthesis, current endeavors aiming to understand co-translational events have been hindered by technological limitations.

By employing high resolution ribosome profiling technique, we are interested in addressing a number of outstanding questions during ribosome elongation. Such co-translational events include co-translational folding, co-translational degradation, and co-translational chaperone interaction. In addition, we study ribosome dynamics in response to various stress conditions.

    Chaperone Network in Protein Homeostasis

Molecular chaperones and ubiquitin-proteasome degradation pathway represent two main systems that protect eukaryotic cells against the buildup of unfolded polypeptides.  Failure to eliminate misfolded proteins in cells can result in aggregates associated with conformational diseases such as Parkinson’s and Huntington’s.

We discovered distinct functions of chaperones in the metabolism of misfolded proteins.  Currently we are creating high-content shRNA library, aiming to identify regulators (repressor and enhancer) of misfolded protein aggregation at a genome-wide scale.