Chang Liu Brings Synthetic Biology Expertise to UCI

Chang Liu was hired as an assistant professor in BME in January by the Center for Complex Biological Systems. Professor Liu received his bachelor’s degree in chemistry with highest honors, summa cum laude at Harvard University, and his doctorate in chemistry at the Scripps Research Institute. He was most recently a Miller Fellow at the Miller Institute for Basic Research in Science at UC Berkeley.

Professor Liu’s research focuses on the engineering of genetic systems. His doctoral work focused on expanded genetic codes and their use to evolve proteins, including anti-HIV antibodies, containing novel unnatural amino acids. In the natural genetic code, 20 amino acids are used, each assigned to a three-base sequence of DNA called a codon. Genetic engineering has allowed codons to be reassigned to specify new, unnatural amino acids and thus create completely new biological functionality. Liu was successful in the genetic encoding of sulfotyrosine in E. coli, which enabled a new avenue to study this common posttranslational modification. Furthermore, Liu leveraged his expanded genetic codes to ask the question of whether additional amino acids could provide a selective advantage in protein evolution. He found that by utilizing sulfotyrosine and other unnatural amino acids, he could generate stronger antibodies against HIV and other disease targets. This work is described in first-author papers published in leading journals such as Nature Biotechnology, PNAS, JACS, and Annual Reviews of Biochemistry. During his postdoctoral training, Liu expanded his expertise into the field of synthetic biology. Specifically, he exploited regulatory leader peptides to control gene expression in a programmable way, allowing cells to respond to environmental stimuli based on Boolean logic operations and higher-order functional relationships. This work has been published as first-author papers in Nature Biotechnology and Nature Methods, with additional papers to come.

Looking forward, Liu is aiming to improve the process of directed evolution, in which we harness the power of natural selection to create genes and proteins with characteristics that are defined by the scientist, rather than nature. Currently, this is a slow process because mutations must be introduced slowly, or else the genome of the host cell becomes compromised too quickly. Liu’s vision is to create an orthogonal genetic system. That is, the host cell will still have its own natural DNA and its own genetic machinery for duplicating and reading its genome; this natural genetic machinery will function with a low error rate, keeping the host cells healthy. At the same time, Liu will introduce a separate genetic system with completely new replication machinery. The two sets of genetic machinery will be separate and will not replicate each other. Thus, the second set of genetic machinery can be engineered to replicate genes using a high error rate, allowing for very rapid evolution of desired genes while protecting the integrity of the natural host genome. This will represent a seminal advancement and transform directed evolution into a much more powerful tool than it is currently.

Liu will provide the BME department with a formidable foothold in the burgeoning field of synthetic biology. Over the past five to 10 years, a number of leading research institutions have begun investing resources into developing programs in synthetic biology. Liu’s unique expertise will make him a powerful collaborator not only within the department, but also cross-departmentally through the Center for Complex Biological Systems.