Dr. P. Shing Ho Laboratory
The Dr. P. Shing Ho Laboratory is where I did scientific research from May 2000 – September 2004.
Note: Dr. Ho was a Professor & Chair of the Department of Biochemistry & Biophysics at Oregon State University while I did my research from 2000 to 2004. He has since moved to Colorado State University as Professor & Chair of the Department of Biochemistry & Molecular Biology.
A program had been written in Fortran (by Dr. P. Shing Ho) to study which sequences were good at forming Z-DNA. The predictions were shown to be good and have been published in numerous papers since 1984. This program (called "ZHunt"), however, could only handle relatively small sequences and was slow. Thus, in May of 2000 I began to adapt the program to allow for sequences as large as chromosomes and small genomes (here human chromosome 22 and E. coli). The original Fortran program was converted into C (with the help of Tracy Camp and Sandor Maurice) and optimized for speed and memory usage. Various other programs were written to analyze the enormous amount of data returned from ZHunt. As an example of the amount of data generated, human chromosome 22 (with ~35 Mbp of annotated sequence at time of writing) when run through ZHunt produces around 6 GB of data. This data must be stored, organized, data mined, interpreted, and presented in a reasonable and clear manner. In order to do this, a MySQL database was employed and various programs were written (in C) to analyze the data. Other programs were written to analyze the association of Z-DNA with known promoter sequences (such as Nuclear Factor I). Thus, this research project—over a four year period—could very well be considered a unison of biochemical and biophysical science with computational know-how; in short, bioinformatics.
- ZHunt Online Server
- DNA topology
- DNA supercoil
- Linking number
- DNA Gyrase — adds negative supercoils to DNA using ATP hydrolysis for energy (9 kcal/mole). 200bp of DNA wrap around the gyrase holoenzyme molecule, ATP is bound, and each strand is cut (staggered cuts) and covalently linked to different tyrosines to "anchor" the DNA.
- DNA gyrase inhibitors:
- - nalidixic acid (prevents strand cutting and rejoining); and
- - novobiocin (blocks ATP binding)
- CCAAT-Enhancer-Binding Proteins
- Macrophage Colony-Stimulating Factor
- Möbius strip
The research I did in this laboratory yielded a paper published and a Web Server:
- Programmer; May 2000-September 2004 (note: Website by Sandor Maurice)
- P. Christoph Champ, Sandor Maurice, Jeffery M. Vargason, Tracy Camp, and P. Shing Ho (2004). Distributions of Z-DNA and nuclear factor I in human chromosome 22: a model for coupled transcriptional regulation. Nucleic Acids Research, 32(22):6501-6510 DOI:10.1093/nar/gkh988 . [HubMed]
- → Liu H, Mulholland N, Fu H, Zhao K (2006). Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling. Mol Cell Biol, 26(7):2550-9.
- → Ha SC, Lowenhaupt K, Rich A, Kim YG, Kim KK (2005). Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases. Nature, 437:1183-1186.
- → Kwon JA, Rich A (2005). Biological function of the vaccinia virus Z-DNA-binding protein E3L: Gene transactivation and antiapoptotic activity in HeLa cells. Proc Natl Acad Sci USA, 102:12759-12764.
- Ho PS (1994). The non-B-DNA structure of d(CA/TG)n does not differ from that of Z-DNA. Proc Natl Acad Sci USA, 91(20):9549-9553.
- Ho PS, Ellison MJ, Quigley GJ, Rich A (1986). A computer aided thermodynamic approach for predicting the formation of Z-DNA in naturally occurring sequences. EMBO J, 5(10):2737-2744.