Stuart Lindsay is the director of the Center for Single Molecule Biophysics at the Biodesign Institute at Arizona Arizona State University. Credit: The Biodesign Institute at Arizona State University
Some three billion base pairs make up the human genome—the floor plan of life. In 2003, the Human Genome Project announced the successful decryption of this code, a tour de force that continues to supply a stream of insights relevant to human health and disease.
Nevertheless, the primary actors in virtually all life processes are the proteins coded for by DNA sequences known as genes. For a broad spectrum of diseases, proteins can yield far more compelling revelations than may be gleaned from DNA alone, if researchers can manage to unlock the amino acid sequences from which they are composed.
Now, Stuart Lindsay and his colleagues at Arizona State University’s Biodesign Institute have taken a major step in this direction, demonstrating the accurate identification of amino acids, by briefly pinning each in a narrow junction between a pair of flanking electrodes and measuring a characteristic chain of current spikes passing through successive amino acid molecules.
By using a machine learning algorithm, Lindsay and his team were able to train a computer to recognize bursts of electrical activity representing the momentary binding of an amino acid within the junction. The noise signals were shown to act as reliable fingerprints, identifying amino acids, including subtly modified variants.
Proteins are already providing a wealth of information pertinent to diseases including cancer, diabetes and neurological disorders like Alzheimer’s, as well as furnishing key insights into another protein-mediated process: aging.
The new work advances the prospect of clinical protein sequencing and the discovery of new biomarkers—early warning beacons signaling disease. Further, protein sequencing may radically transform patient treatment, enabling precise monitoring of disease response to therapeutics, at the molecular level.
The group’s research results are reported in the advanced online edition of the journalNature Nanotechnology.
From genome to proteome
An enormous library of proteins—known as the proteome, occupies center stage in virtually all life processes. Proteins are vital for cellular growth, differentiation and repair; they catalyze chemical reactions and provide defense against disease, among myriad housekeeping functions.