Sitting at a microscope for hours while painstakingly searching for the right cell may soon become a methodology of the past, thanks to software developed by researchers at the European Molecular Biology Laboratory (EMBL). The EMBL scientists have developed a computer program called Micropilot that rapidly learns what the scientist is looking for and automatically performs the complex microscopy experiment when it detects cells with particular features. With the ability to incorporate machine learning, Micropilot can analyze low-resolution microscopy images. Once it has identified a cell or structure of interest to the scientist, it will automatically instruct the microscope to conduct the experiment. The procedure can be as simple as recording high-resolution time-lapse videos, or as complex as using a laser to interfere with fluorescently tagged proteins and recording the results. EMBL’s software Micropilot can detect cells at particular stages of cell division (each row shows one cell). It instructs the microscope to remove fluorescent tags from proteins in half the cell’s nucleus (left), and records what happens next (middle and right). Courtesy of EMBL. Eliminating the laborious and time-consuming task of searching for cells, the software can easily and quickly generate enough data to obtain statistically reliable results. In just four nights of unattended microscope operation, Micropilot detected 232 cells in two specific stages of cell division and performed a complex imaging experiment on them, a feat that normally would take a full-time experienced microscopist at least a month. The observation should help scientists probe the role of various proteins in a specialized biological process. The EMBL teams that designed the software have used it to deploy several types of microscopy experiments investigating different features of cell division. They were able to detect when endoplasmic reticulum exit sites form, and discovered the roles of two proteins, CBX1 and CENP-E, in condensing genetic material into tightly wound chromosomes and in forming the spindle that helps align those chromosomes. Their findings were reported online Jan. 23, 2011, in Nature Methods (doi: 10.1038/nmeth.1558).