MARCH 2015
Potential Discovery of New Protein Therapeutics
Prof Mingjie Zhang (middle) and the IAS HKUST-Scripps researchers in Hong Kong.

A team of scientists at the IAS HKUST-Scripps R&D Laboratory has discovered 250 new proteins with previously unidentified activities. Prof Mingjie Zhang, Kerry Holdings Professor of Science, IAS Senior Fellow and Division of Life Science, and Prof Paul Schimmel, the Ernest and Jean Hahn Professor of Molecular Biology and Chemistry at the Scripps Research Institute (California and Florida) and a visiting professor of the IAS, co-authored the research paper.

“The breakthrough finding not only uncovers a vast area of new biology, but also provides opportunities to develop protein-based drugs for various human diseases associated with malfunctions of these newly discovered proteins,” said Prof Zhang. Detailed findings were published in Science in July 2014.

After six years of research study in a protein-building enzyme called aminoacyl tRNA synthetase (AARS), the team discovered more than 250 previously-unidentified AARS variants in different human cell types with activities spanning from stem cell biology to immunology. This highlights an intriguing oddity of protein evolution as well as a potentially valuable new class of therapeutic proteins.

Further investigations to understand this enzymatic gene family now leads the team to a completely new horizon for human physiology, such as stem cell biology, immune pathways, vascularization and metabolism.

The team is undergoing more comprehensive studies of the new AARS variants and their specific functions. They believe that these proteins have relevance to multiple human diseases, representing an important class of new protein therapeutics analogous to widely-used injectable protein therapeutics such as growth hormone, insulin, erythropoietin (which regulates red blood cell production) and granulocyte colony-stimulating factor (which stimulates the bone marrow).



Prof Paul Schimmel.
Muscle fibers were significantly increased in the AARS splice-variants-treated human skeletal muscle cells (below).