By many accounts, physics is going to drive many of the breakthroughs in molecular biology during the next 20 years and beyond. Likely to lead that push is Taekjip Ha, who is developing novel physical methods to tag and manipulate single molecules to evaluate their behavior and interactions.

Ha uses physical techniques to study the mechanism of helicases, DNA-unwinding enzymes that crawl along the DNA helix, separating the double strands as they go. Helicases are important in many genetic processes; when they malfunction, genetic diseases or cancer may follow.

Ha is pioneering fluorescence resonance energy transfer (FRET), a relatively new technique, that relies on transferring energy between donor and acceptor fluorescent tags on different parts of a molecule to reveal stunning details about the conformational changes molecules undergo during biological processes. Ha's FRET studies have revealed new information about how helicase moves along a DNA molecule as it unwinds the strands.

Not content to be confined to the realm of less applied biology, Ha has branched out to use FRET and other new tools to study malfunctioning helicases in human genetic disease. He has also studied the role helicases play in the large protein complexes that regulate chromatin remodeling, a process that regulates gene expression by controlling access to DNA in genes.

Ha also uses FRET to study how RNA enzymes called ribozymes fold from a string-like conformation into the globular shape that enables them to function. Ribozymes are believed to have evolved before the protein enzymes that are now considered the workhorse catalytic molecules of cells.

Using other single-molecule fluorescence techniques in combination with advanced microscopes and manipulation techniques, Ha studies how malfunctions occur in chromosome separation during meiosis, the process that produces sperm and eggs. Such breakdowns are a major cause of birth defects and the leading cause of miscarriages.