The BioMicro Center provides state-of-the-art microarray and data mining technology. The following summaries illustrate some of the research projects utilizing the BioMicro Center.

John Essigmann (Biological Engineering) is studying the expression of genes that are up regulated, down regulated and not affected by treatment of human cells with aflatoxin B1 are determined. In parallel, DNA containing enriched DNA adduct pools (e.g., DNA enriched with the aflatoxin-FAPY adduct) is introduced into cells by transfection to determine the elements of the transcriptional response that may be specific to individual adducts. The hypothesis tested is that there will be certain gene expression patterns that reflect the level and type of challenge to the cell from this toxin. (expanded research description)

James Fox (Biological Engineering) is examining the mechanisms by which chronic infection with environmentally acquired pathogens causes cancer in humans. One of these organisms, H. hepaticus, causes chronic, active hepatitis and liver cancer in A/JCr mice, as well as dysplasia and colon cancer in other mouse models. Using H. hepaticus oligo arrays printed using Core facilities, they confirmed the identity of the strains (DNA hybridization) and quantified H. hepaticus expression levels (mRNA hybridization) in liver samples from the A/J mice; cultured cells as well as colon tissue will be analyzed shortly. (expanded research description)

Linda Griffith (Biological Engineering) is looking at the responses of the liver bioreactor to those of native liver under treatment by toxicants. Transcriptional profiling is used to compare responses of cells maintained standard cell culture methods, perfused bioreactor, to those in vivo. The first phase of the project focused on methods development for conducting transcriptional profiling of the rat tissue obtained from the bioreactor. (expanded research description)

ChoKyun Rha (Biomaterial Science and Engineering) is investigating the gene expression profiles of human cells in response to compounds isolated from Centella asiatica and Eurycoma longifolia, two Malaysian plants of pharmaceutical interest. In addition, the laboratory focuses on the Eukaryotic response to cellular stress and aging by studying Saccharomyces cerevisiae. (expanded research description)

Leona Samson (Center of Environmental Health Science) is investigating the gene expression and phenotypic analysis of E. coli, yeast and mice. One of these projects is entitled, Transcriptional Responses of Mice to Alkylating Agents, has a major goal of painting an integrated picture of how mammalian cells, in culture and in the intact organism, respond upon exposure to alkylating agents. The specific agents are chosen to represent environmental toxicants as well as those commonly used for chemotherapy. (expanded research description)

David Schauer (Biological Engineering) is examining the expression profiles of hepatocytes following infection with the cancer-causing bacterium Helicobacter hepaticus. Male A/J mice, which are susceptible to Helicobacter hepatitis and hepatocellular carcinoma, are experimentally infected with H. hepaticus, and are euthanized 6 to 12 months later. Preliminary results indicate that H. hepaticus infection induces expression of a number of genes involved in apoptosis, protein synthesis, and DNA replication in isolated hepatocytes. (expanded research description)

James Sherley (Biological Engineering) is studying the genes that are specifically up-regulated during asymmetric cell kinetics. Asymmetric cell kinetics are a characteristic of adult stem cells. Therefore, their hypothesis is that some genes that are specifically up-regulated during asymmetric cell kinetics may also identify adult stem cells. Currently, genes that uniquely identify adult stem cells have not been discovered. The identification of such genes is highly desired in efforts to identify, isolate, and manipulate adult stem cells for new therapies. (expanded research description)

Phillip Sharp (CCR) is examining the Oct-1transcription factor that interacts with a DNA binding motif termed the octamer. The octamer motif present in the gene regulatory regions (promoters) is both ubiquitous (H2B, snRNA) and cell type-specific (immunoglobulin, Il-2) genes. In a number of these cases, the octamer has been shown to be functionally important for the expression of those genes. We have investigated the physiological role of Oct-1 through the use of gene knockout technology. (expanded research description)

Anthony Sinskey (Biology) is looking at metabolic engineering in Corynebacterium glutamicum: C. glutamicum is a nonpathogenic, gram-positive, food-grade microorganism with a long fermentation history, and thus is potentially useful as a host strain for producing a number of recombinant DNA products. We have developed fundamental genetic tools enabling one to directly address questions of gene organization, structure and regulation at the molecular level. The primary objectives of recent research include using DNA microarrays and functional genomics to dissect the genetic elements responsible for amino acid production in Corynebacterium. (expanded research description)