We are using genome-wide expression analysis with mutations in various components of the yeast transcription initiation apparatus to identify the genome expression signature produced by defects in each component. The genome control map derived from this data describes the set of components of the transcription apparatus which are responsible for regulation of each gene, and the set of genes which are coordinately controlled by each transcription factor. The target of signal transduction pathways can be deduced by comparison of the genome expression signature produced by altering the environment of the cell and the signatures produced by mutations in each component of the transcription apparatus. In this and in other ways, the genome control map is fundamental for interpreting the biological meaning of data from genome expression monitoring. Such information will lay the foundation for understanding how the cell responds to the environment by remodelling gene expression throughout the genome.
Macrophage are frequently the first line of immune defense against infection.
Mycobacterial diseases are among the oldest infectious diseases described, and they remain among the most important causes of human morbidity and mortality worldwide. For example, the World Health Organization estimates that one-third of all humans are currently infected with Mycobacterium tuberculosis . HIV is the cause of the AIDS epidemic, and many important questions remain to be answered about HIV pathogenesis. We would like to know more about the biology of these infectious agents and the macrophage that attempt to control them. We are investigating the changes in gene expression exhibited by the host and the pathogen after infection to obtain clues to the nature of the interactions between mycobacterial and HIV pathogens and their host cells.