Managing Gene Behavior Helps Cells to Excel
Researchers with the Synthetic Biology Engineering Research Center (SynBERC), an NSF-funded center headquartered at the University of California at Berkeley, have developed a new system for controlling gene expression in an organism. Gene expression is the process by which information from a gene is used in the synthesis of large biological molecules that perform a vast number of functions within living organisms. It is used by all known life.
The ability to control gene expression in an organism is an essential goal of synthetic biology. Gene expression is used in the synthesis of functional biochemical material, i.e., ribonucleic acid (RNA) or protein. RNA is a ubiquitous family of large biological molecules that perform vital roles in the coding, decoding, regulation, and expression of genes. Proteins are large biological molecules, or macromolecules, consisting of one or more chains of amino acid residues. Proteins perform a vast array of functions within living organisms, including catalyzing metabolic reactions, replicating DNA, responding to stimuli, and transporting molecules from one location to another. Control of the process of gene transcription affects patterns of gene expression, allowing a cell to adapt to a changing environment, perform specialized roles within an organism, and maintain basic metabolic processes necessary for survival.
The SynBERC researchers collaborated with a number of investigators to tailor a naturally occurring genome editing system named CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to interfere with the expression of multiple genes within an organism, tissue, or cell. This system, CRISPRi, is compact and can be used in both bacterial and mammalian cells.
The SynBERC investigators altered a CRISPR component, Cas9, to “home” to a specific genomic sequence via associated RNA and then “park” on the target gene. This prevented it from being transcribed by RNA polymerase enzymes, effectively silencing gene expression. The investigators also showed that CRISPRi can be made capable of being formed, activated, or expressed and that it is remarkably specific in E. coli. The CRISPRi system can be used in a general genetic programming platform that is suitable for a variety of applications, including genome-scale functional profiling, microbial metabolic engineering, and cell reprogramming.