Zhang, Zhiwen Jonathan, Ph.D.
Assistant Professor
BME 6.202E
512-471-4551
zhang@mail.utexas.edu

The research in Zhang lab is scientific question-oriented biotechnology development. In general, we are studying weak and transient protein-protein interactions that are regulated by posttranslational modifications (PTMs).

Biological questions:

1. Molecular and cellular mechanism of transpeptidase Sortase A. Sortase A is a therapeutically important enzyme, whose function is to anchor virulence factors to the cell walls of gram-positive bacteria. Thus, compounds that can disrupt sortase A activity may function as a new class of antiinfectives to battle methicillin-resistant Staphylococcus aureus (MRSA). We have recently discovered that sortase A is a dimeric protein both in vitro and in vivo and proposed its molecular and cellular mechanism (see Figure 1). Our study indicates that Sortase A dimer is the more accurate target for the future drug development.

2. Posttranslational modification regulated cellular translocation of oncogene c-Myc. We hypothesize that the interplay of phosphorylation and glycosylation on the certain sites of c-Myc serves as signals for the translocation of this oncogene in-and-out of nucleus. We would like to decipher these “ PTM codes”.

Biotechnology development:
1. trM2H system. A highly sensitive and small molecule-regulated mammalian two-hybrid system has been developed to detect weak protein-protein and peptide-peptide interactions in vivo. We are engineering trM2H system as a tool kit to measure the dissociation constants of protein-protein interactions in mammalian cells; we are applying trM2H system to detect PTM-mediated protein-protein interactions in the nucleus such as phophorylation, glycosylation, SUMOylation and methylation.

2. Synbody (synthetic antibody) Engineering. Combination of biocomputational method and trM2H system allows us to identify peptide(s) that bind specifically to peptidic domain, e.g. Abl SH3 domain. Such synthetic peptide(s) can be engineered to mimic the functions of antibodies.  

3. Site-specific protein crosslinking. A site-specific protein crosslinking technology using genetically encoded 3,4-dihydroxyphenylalanine (L-DOPA) has been developed to map the interacting domain and residues of  protein-protein interactions with excellent specificity.

4. Reverse protein engineering: Before the protein world, I believe there is a peptide world. We hypothesize that, to a certain degree, peptides can be created that mimic the functions of larger proteins. This type of peptide could then serve as a template for further modification and enhancement using organic chemistry. To test this notion, we have been working on developing a peptidic GFP molecule.

5. Expanding the genetic code in mammalian cells: We would like to design and/or evolve novel genetic codes specific for unnatural amino acids in mammalian cells.

EZ Plasmid Map is an application developed in the the Zhang lab by Liang Xiang. It allows the user to quickly draw, label, and export a publishable plasmid map. It allows the user to add/reposition/edit restriction sites and genes using an intuitive user interface.

Requirements for use are a Web-browser with Flash Player 9.0 or newer (newest update of Flash Player recommended). It is available free of charge, but the developers request that when using the application to create images for publication you credit their lab with the following citation: EZ Plasmid Plotter. Zhang Lab, The University of Texas at Austin, BME