Our project attacks the following problem: can one engineer viruses to selectively kill or modify specific subpopulations of target cells, based on their RNA or protein expression profiles? This addresses an important issue in gene therapy, where viruses engineered for fine target discrimination would selectively kill only those cells over- or under-expressing specific disease or cancer associated genes. Alternatively, these viruses could be used to discriminate between strains in a bacterial co-culture, allowing strain-specific modification or lysis. This is clearly an ambitious goal, so we brainstormed a simple model of this problem suitable for undergraduates working over a summer. The bacteriophage ? is a classic, well studied virus capable of infecting E. coli, another classic model genetic sytem. We therefore seek to engineer a ? strain targeted to lyse specific subpopulations of E. coli based on their transcriptional profiles. Together, ? and E. coli provide a tractable genetic model for this larger problem, while hopefully providing lessons applicable to more ambitious, future projects.