The long-term goals in systems biology laboratory include (1) the development of an integrated and iterative set of experimental and computational tools that can be used to understand and model gene regulatory networks/pathways in microbial systems; (2) the development of an integrated informatics framework for emerging and re-emerging infectious diseases; (3) the development and validation of a complete RNA motif prediction software package. Currently, my laboratory is focusing on the following three directions:

(1) Understanding iron assimilation pathways by integrating computational prediction and experimental validation. Iron is one of the essential nutritional elements for bacteria. Understanding iron uptake pathways may reveal the environmental adaptation for bacteria and even the pathogenesis mechanisms for some microbial pathogens. Previously, we defined the fur modulon in Shewanella oneidensis MR-1, a metal reducing bacterium with bioremediation potential, by integrating genome-wide expression analysis, proteome characterization, and regulatory motif discovery. We generated the hypotheses that fur would act as a positive regulator in S. oneidensis. My laboratory is now trying to further understand the detailed regulation mechanisms of fur as positive regulator in S. oneidensis by integrating computational studies and wet lab experiments, which includes both traditional biochemical techniques and the high throughput techniques such as microarray and proteomics. By comparative genomics and computational modeling, we hope to understand the siderophore-mediated iron assimilation pathway in S. oneidensis. My laboratory is also interested in the iron assimilation pathway in several other pathogenic bacteria.

(2) Understanding avian influenza viruses and their evolutional footprints. Influenza A is a negative strand RNA virus with 8 genomic fragments (HA, NA, PA, PB1, PB2, NP, NS, and M). Genetic shift and genetic drift has led to a rapid emergence of novel genotypes of avian influenza viruses during their evolution. However, there has not been available an efficient and effective approach to characterize genetic reassortments and other evolutional patterns between Influenza A viruses. I am very interested in developing and then applying new quantitative methods to define and identify the genetic reassortment and other evolutional patterns of influenza A viruses. Beyond this, by integrating wet laboratory experiments with computational modeling, my laboratory would begin to explore the connection between genotype, phenotype, and epidemiology, especially, in influenza A viruses. Currently, my laboratory focuses on the avian influenza viruses that cause human infection, such the H5N1 avian influenza virus. Recently, H3N2 avian influenza virus has been isolated in Turkey, thus it is one of my interests as well. My laboratory will be interested in other RNA viruses, such as coronavirus (e.g. SARS-CoV), HIV, and West Nile virus as well.

(3) Identification and functional analyses of RNA motifs. RNA structural motifs may function in various biological processes. For example, the hairpin-loop structure at the end of an mRNA can act as intrinsic terminators, which serves as an economic transcriptional termination machinery in bacteria. Many of conserved local secondary structures are also found in viral RNAs. Thus, predicting RNA structural motifs can shed some light on the biological mechanisms of viruses and may rapidly provide information for virus control and treatment, especially for emerging viral diseases. Previously, I have developed a software package Rnall for RNA local secondary structure prediction as well as the intrinsic terminator prediction. Currently, my laboratory focuses on the distribution and evolutional footprints of intrinsic terminator in prokaryotes. We will iteratively optimize the computational algorithms for intrinsic terminator prediction by experimental validation. My laboratory will also be interested in identifying and functionally characterizing other RNA motifs in genomic scale, such as riboswitch, various RNA motifs in viruses, RNAi, and splicing sites.