- James C. Hu
- BioBio / Room 443A
- Undergraduate Education
- B.S. Stanford University (1975)
- Graduate Education
- Ph.D. University of Wisconson (1987)
Protein interactions/Microbial Genomics and Annotation
Multisubunit proteins are involved in every aspect of life. We use biochemical, biophysical, genomic, and molecular genetic approaches to identify and study protein interactions. We are studying two families of proteins to understand how the specificity of assembly is used to distinguish proteins with similar tertiary structures. Leucine zippers are short alpha-helical coiled-coils that hold together the dimers in many eukaryotic transcription factors. LysR-Type Transcriptional Regulators (LTTRs), which form homotetramers, are one of the most common types of bacterial transcription factors. Understanding how leucine zippers and LTTRs form specific homo- and heterooligomers will help us understand the principles of protein architecture and evolution, and may allow us to develop new tools to modulate gene expression.
We are also using a genetic approach to screen whole genomes for new oligomeric proteins and protein domains. We have identified hundreds of oligomerization domains from E. coli, the yeast Saccharomyces cerevisiae, and two important bacterial pathogens, Mycobacterium tuberculosis and Pseudomonas aeruginosa. We are using these domains to develop new approaches to functional genomics and the discovery of new antibiotics based on blocking the assembly of specific protein complexes.
Our genome-wide studies of protein interactions and E. coli proteomics have led us to appreciate the importance of continuous updating of genome annotation, We are using “new media” to build systems for the scientific community to participate in updating the annotation of every gene from any organism (but with special focus on E. coli).
EcoliWiki an be thought of as “Wikipedia for E. coli”, while the Gene Ontology Normal Usage Tracking System (GONUTS) is a wiki to allow scientists to use and understand the Gene Ontology system for functional annotation.
Chibucos, MC, Siegele, DA, Hu, JC, Giglio, M. The Evidence and Conclusion Ontology (ECO): Supporting GO Annotations. Methods Mol. Biol. 2017;1446 :245-259.
Gaudet, P, Škunca, N, Hu, JC, Dessimoz, C. Primer on the Gene Ontology. Methods Mol. Biol. 2017;1446 :25-37.
Nehring, RB, Gu, F, Lin, HY, Gibson, JL, Blythe, MJ, Wilson, R et al.. An ultra-dense library resource for rapid deconvolution of mutations that cause phenotypes in Escherichia coli. Nucleic Acids Res. 2016;44 (5):e41.
Chibucos, MC, Zweifel, AE, Herrera, JC, Meza, W, Eslamfam, S, Uetz, P et al.. An ontology for microbial phenotypes. BMC Microbiol. 2014;14 :294.
Hu, JC, Sherlock, G, Siegele, DA, Aleksander, SA, Ball, CA, Demeter, J et al.. PortEco: a resource for exploring bacterial biology through high-throughput data and analysis tools. Nucleic Acids Res. 2014;42 (Database issue):D677-84.
Brister, JR, Le Mercier, P, Hu, JC. Microbial virus genome annotation-mustering the troops to fight the sequence onslaught. Virology. 2012;434 (2):175-80.
Renfro, DP, McIntosh, BK, Venkatraman, A, Siegele, DA, Hu, JC. GONUTS: the Gene Ontology Normal Usage Tracking System. Nucleic Acids Res. 2012;40 (Database issue):D1262-9.
McIntosh, BK, Renfro, DP, Knapp, GS, Lairikyengbam, CR, Liles, NM, Niu, L et al.. EcoliWiki: a wiki-based community resource for Escherichia coli. Nucleic Acids Res. 2012;40 (Database issue):D1270-7.
Knapp, GS, Hu, JC. Specificity of the E. coli LysR-type transcriptional regulators. PLoS ONE. 2010;5 (12):e15189.
Knapp, GS, Hu, JC. The oligomerization of CynR in Escherichia coli. Protein Sci. 2009;18 (11):2307-15.