Joung Lab

The Joung lab studies how naturally occurring transcription factors mediate specific interactions with DNA and other proteins (molecular recognition) and uses bacterial cell-based selection methodologies to construct synthetic “designer” transcription factors (protein engineering). 

Our efforts focus primarily on Cys2His2 zinc fingers, the most common structural motif found in eukaryotic transcription factors.  Cys2His2 zinc finger proteins mediate specific protein-DNA and protein-protein interactions, many of which are central to normal and disease-related cell processes.  In addition, selection and design methods have been used to engineer synthetic Cys2His2 zinc fingers capable of recognizing novel DNA sequences of interest.

Structure-function studies of biologically important zinc finger proteins

We use a combination of genetic, biochemical, structural, and mammalian cell-based approaches to gain a physical-chemical understanding of DNA and protein recognition mediated by biologically important zinc finger proteins.  Two major projects in the lab focus on studying the recognition of extended DNA sequences by the NRSF/REST zinc finger repressor and on understanding how zinc fingers in the Ikaros family of transcription factors mediate specific homo- and hetero-typic interactions.  

Engineering “designer” zinc fingers with novel DNA-binding specificities 

The Joung lab is a founding member of The Zinc Finger Consortium (http://www.zincfingers.org).  As part of this effort, we are developing high-throughput methods for rapidly engineering synthetic zinc finger domains with novel, defined DNA-binding specificities.  These “designer” zinc fingers provide powerful tools for biological research and potentially for gene therapy as they can be used to target functional domains to any desired gene of interest.  For example, designer zinc fingers fused to a non-specific endonuclease domain can be used to introduce double-stranded DNA breaks into specific genomic loci in mammalian or plant cells.  The site-specific breaks introduced by such “zinc finger nucleases” can be used to promote gene correction or gene mutation of specific endogenous genes.  We are also exploring the use of large combinatorial libraries of zinc finger transcription factors to screen for specific phenotypic changes in cells ranging from bacteria to humans.