The Cover Article, entitled "Using protein-DNA chimeras to detect and count small numbers of molecules," describes "tadpole" molecules, and their use to detect and count small numbers of proteins and other molecules.
Detection and quantification methods based on these molecules have exquisite sensitivity, immense dynamic range, and unprecedented quantitative precision. These attributes should make the molecules useful for applications from diagnosis and assessment of human disease, to environmental monitoring, to detection of pathogens during an emerging infectious disease or a deliberate biological attack.
Methods based on these molecules are designed to work with the existing infrastructure of PCR machines, which are widely deployed and found most county public health departments in the United States.
According to Dr. Roger Brent, MSI Director and senior member of the team, "We called the molecules tadpoles because they consist of a protein head coupled to a DNA tail. The head binds the specific target molecule, while the DNA tail lets us count the number of target molecules."
Dr. Ian Burbulis, a researcher at MSI, devised the tadpole molecules and is the first author of the paper. According to Dr. Burbulis, "If you want to understand the mechanistic operation of biological systems, you need to know the precise numbers of each component part found in individual cells. Tadpoles and methods based on them should make that possible."
To count molecules so precisely, the researchers resorted to statistical methods sometimes used in high energy physics. The improved statistical techniques may be useful in other applications, such as management of therapy for HIV.