Helicobacter pylori 26695 Structural Genomics

Collaboration with Prof. Jya-Wei Cheng,
Institute of Biochemistry, National Tsing Hua University.

Structural genomics is a new and rapidly developing field in life sciences. The goal of this field is to discover and analyze the structures as well as functions of all proteins in nature in order to provide a foundation for a fundamental understanding of biology. Several genome projects have been finished recently. The next step of genomic studies after the yielding of the complete genome sequence of a species is to identify both cellular and molecular function of each gene in the genome. Several pilot projects in structural genomics are on the way. The preliminary results from these pilot projects show complementary data with functional genomic analysis. Both approaches are important for genome research beyond DNA sequencing. In this program project, we propose to develop and incorporate the methodologies and technologies for structural genomics and proteomics studies on Helicobacter pylori and its associated proteins involved in cell cycle. The target selection is based on that Helicobacter pylori is a microaerophilic Gram-negative bacterium that colonizes the stomachs of an estimated half of all humans and the genome size (1.6 Mb, total genes 1576) of Helicobacter pylori is relatively small and suitable for a structural genomics and proteomics studies. Also, the genomes of the two unrelated strains íV 26695 and J99 were sequenced in their entirety and are available for high-throughput, large-scale protein cloning and expression and little has been done on the proteomics especially structural genomics studies of Helicobacter pylori. We have already set up a bioinformatics web site for Helicobacter pylori. With the help from bioinformatics, high throughput cloning, expression, and purification of target proteins, structural analysis by various biophysical techniques and proteomics studies on the cellular function of Helicobacter pylori, we anticipate to solve about 10-20 novel protein structures each year.

In addition to the structural genomics studies, specific proteins for cellular responses induced by Helicobacter pylori or its major virulence factors by comparative studying of differential protein expression profiling both in sub-cellular organelles and whole cells will be studied by using the proteomics approaches such as 2D gel, mass spectroscopy, confocal microscopy, etc. The completion of this project will expand our understanding of the atomic basis of Helicobacter pylori, provide significant shortcuts to understanding its gene function, and generate the most fundamental genomic data besides the sequence information itself. The structure-function information would ultimately aid in understanding the molecular mechanism of cellular response to Helicobacter pylori infection. Furthermore, the findings from this project may provide insight to the prevention and treatment of diseases associated with Helicobacter pylori.