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Lei Wang

 

Lei Wang

Lei Wang

Assistant Professor and Frederick B. Rentschler Developmental Chair
Chemical Biology and Proteomics Laboratory

"We are trying to insert artificial amino acids into proteins in mammalian cells and multicellular organisms, because novel properties of these amino acids will enable us to explore a variety of biological processes at the molecular level with great precision and accuracy. We are currently focusing on studying how stem cells differentiate and how cells communicate with each other during development."

Cells provide a dazzling variety of functions that cover all of our body's needs, yet they make do with a very limited number of molecular building blocks. With few exceptions, all known forms of life use the same common 20 amino acids—and only those 20—to make all the proteins necessary to keep alive organisms as diverse as humans, earthworms, tiny daisies, and giant sequoias. Using nature's own techniques, Wang developed a novel strategy to expand the natural repertoire of 20 amino acids in bacteria and successfully inserted tailor-made amino acids into proteins in these cells. However, most biomedical questions have to be studied in the cells of higher organisms and animal models to arrive at meaningful answers.

During protein synthesis, amino acids are brought out one by one by molecules known as transfer RNAs (tRNA) and added to the growing protein chain according to the instructions spelled out in the genetic code till a stop codon—for which no corresponding tRNA/ amino acid pair exists—lets everybody know that this particular job is done. For his initial study in bacteria, Wang selected an aminoacyl-tRNA synthetase—the enzyme that loads tRNAs with their corresponding amino acids—that would attach a desired artificial amino acid to a tRNA that recognizes one of the stop codons. Every time the stop codon appeared in the genetic code, the tRNA would insert the artificial amino acid that came along with it. But doing the same trick in mammalian cells proved much more complicated.

Coercing mammalian cells to express bacterial tRNAs and relying on yeast to perform the grunt work of finding a synthetase that recognizes tRNA and attaches the right unnatural amino acid helped Wang and his team to overcome the hurdles thrown up by mammalian cells. Then Wang teamed up with Salk professor Paul Slesinger, who studies ion channels in the brain, to illustrate that this technology can solve otherwise intractable biological questions. Inserting modified amino acids into these ion channels not only allowed them to uncover how the gates open or close but also marks the first time that non-natural amino acids were successfully introduced into neurons.

Lab Photo

Left to right:
Zheng Xiang, Bin Shen, June Brennan, Lei Wang, Angela Parrish,David Johnson, Vanessa Lacey, Phillip Kyriakakis, Jeff Takimoto

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Lei Wang

Faculty

Lei Wang

Lei Wang

Assistant Professor and Frederick B. Rentschler Developmental Chair
Chemical Biology and Proteomics Laboratory

Cells use a limited number of molecular building blocks to achieve an amazing variety of functions for life needs. Understanding, utilizing, and enhancing such capabilities depend on how at will we are able to manipulate molecules inside cells. Our laboratory is interested in developing new strategies for molecular evolution and molecular imaging. These new methods will be applied to study cellular functions and to generate new biological activities. We combine chemistry, biochemistry, molecular biology and fluorescence techniques to achieve these goals.

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