A CAMERA flash lasts only thousandths of a second, an incredibly short time. This is painfully slow, however, compared to a somewhat faster flash – lasting a millionth of a millionth of a second – being used to watch what happens when DNA gets damaged, writes DICK AHLSTROM
The discovery of the structure of our genetic blueprint, DNA, by Watson and Crick in the 1950s, still stands as one of the most important biological discoveries of the past century. Yet we still face huge gaps in our understanding of it, says Dr Gerard Doorley, a post-doctoral researcher at Trinity College Dublin.
He won his PhD with a project that used a super-fast imaging system to study in detail what happens when a strand of DNA gets damaged by ultraviolet (UV) radiation. UV from the sun causes damage to DNA in the skin and can lead to cancers, so the more we understand this process the better, he explains.
A presentation in Dublin earlier this week saw Doorley declared the winner of the annual Prize for Young Chemists, a competition organised by the Royal Irish Academy. The award goes to the best chemistry PhD thesis in Ireland, as judged from a 1,000-word essay describing their work.
Aside from winning €1,000 from sponsors Eli Lilly, Doorley now goes forward as Ireland’s representative to a similar international competition organised by the International Union of Pure and Applied Chemistry (IUPAC).
The goal of the research was very simple on the face of it, he says. “We wanted to understand on an ultra-fast timescale what happens to DNA when exposed to UV light.” The problem was how to achieve the timescales, down to a “picosecond”, a millionth of a millionth of a second. This was done using lasers and spectroscopy equipment made available at the Rutherford Appleton Laboratory in Britain with funding from the EU.
DNA is a molecule whose chemical bonds can be broken when struck by high-energy light such as UV. This could present serious problems, including DNA mutation and cancers, were it not for the fact that we have evolved effective DNA repair mechanisms to protect against mutations.
“People understand UV can cause damage, but there is a huge gap between the UV pulse and the outcome,” says Doorley. It’s like reading the first and last chapters of a book, he says.
He is helping to fill this gap by watching, picosecond by picosecond, how DNA is first broken then quickly repaired after UV exposure. When DNA is struck, it absorbs some energy from the UV to cause the break. It must then shed this energy quickly, most of the time returning to its original state, but sometimes with resultant damage.
“We are not only interested in changes that occur but how the molecule returns to a lower energy state,” Doorley says. Researchers built their own “human” DNA strands, copying a 22-step strand found in telomeres – the end bits of a gene – and another from a strand known as the “i motif”. These were then exposed to a 0.2-picosecond pulse from a UV laser to impart a damaging energy to the molecule. A laser, delivering infrared light, was then used to take “pictures” of what happens next.
“We take pictures at one, two, three picoseconds out to a nanosecond or one-thousandth of a millionth of a second,” Doorley says. “We can look at any new transient species produced and the return to the ground state.”
This work may tell us why DNA sometimes can’t repair itself, instead forming mutations that can turn into cancers.
Doorley plans to make use of these advanced techniques when he takes up a research position on April 1st at Georgia Institute of Technology in Atlanta. A result in the IUPAC competition will come later in the year.
Twitter:@dickahlstrom