The art and design of genetic screens: Mammalian culture cells

Given the wealth of sequence information from the Human Genome Project, many open reading frames urgently require assignment of function. Whereas genetic model organisms, such as yeast, Drosophila and Caenorhabditis elegans, have successfully been used in genetic screens for a long time, mammalian culture cells have only recently emerged as a suitable screening system to elucidate gene function. Diverse cellular activities, such as apoptosis, senescence, tissue-specific differentiation and oncogenic transformation, can be studied in cell culture. There is a plethora of functional assays that can provide a link between genes and physiology. The number of genetic elements to be tested necessitates the use of miniaturization strategies or robotic instrumentation for effective screens that use mammalian cell lines.