TXGnet: Harvard Institute of Proteomics.

The discovery, study, and characterization of the vast number of proteins in the human body is an enormous challenge. One research center that has been formed to take on this challenge is the Harvard Institute of Proteomics (HIP). The HIP's website, located at http://www.hip.harvard.edu/, outlines the institute's research program. Founded within the Harvard Medical School in t999, the HIP is at present laying the groundwork for determining the function of every protein encoded by the human genome in order to help understand how protein malformations contribute to disease.

Toward this goal, HIP scientists are developing a novel robotics-based resource known as the FLEXGene repository, which will contain and distribute cloned copies of 20,000 human genes. Once this repository is complete, its developers say it will allow researchers to look at protein expression in all experimental formats and at any chosen scale. Whereas traditional DNA subcloning is time-consuming and labor-intensive, using clones from FLEXGene is quick, inexpensive, and efficient.

The research section of the site contains contact information for and descriptions of the eight areas of ongoing HIP research. One of these, the Breast Cancer 1,000 Project, is focused on discovering and understanding the biological functions of proteins related to breast development and breast cancer. Eventually, this research group will develop a repository of clones for 1,000 full-length complementary DNAs for genes that may contribute to the onset of breast cancer. The group is also working to convert their findings into technologies to support a broad range of functional experiments. The products generated through these efforts should also prove useful to research on other cancers that have been linked to this group of genes.

HIP projects devoted to the sequencing of the genomes of human pathogen organisms and the building of an expression-ready gene repository for these gene sets are described on the Pseudomonas page of the Research section of the HIP site. Currently HIP investigators are focusing on developing gene sets for Pseudomonas aeruginosa PAO1 (the leading cause of death in cystic fibrosis patients), the malaria parasite Plasmodium falciparum 3D7, and strains of arboviruses including West Nile virus and dengue virus strains 2 and 3.

Institute researchers are also pushing forward to clone the entire range of kinases encoded within the human genome and to transfer them to a database that supports cell-based assays relevant to processes including growth factor/cytokine signaling, apoptosis, and immunosuppression. Information on this project is available in the Research section, as are snapshots of projects to develop high-throughput methods for protein expression and purification, and to devise a method for producing protein microarrays that is more streamlined than current processes and that reduces the need for direct manipulation of the proteins.

The Informatics section of the HIP site contains links to databases and web-based programs used for proteomics applications. For example, the MedGene database mines text citations from PubMed to create a "co-occurrence network" that normalizes and ranks reported human gene-disease relationships. MedGene can generate input for disease-specific microarrays, sort gene profiling data, and compile lists of genes for use in screening experiments. The programs available on this page include PCR Oligo Calculator, which lets researchers design batch polymerase chain reaction primers for amplifying the open reading frames for a given set of genes, and Batch Gene Retriever, which allows downloads of full-length sequence information from National Center for Biotechnology Information databases in batch mode.