Expose your skin to the sun for too long without protection, and you’ll get a sunburn. In other words, the sun’s UV radiation will cause an inflammatory response in the exposed skin cells. Get burned too many times and you’re likely to experience premature skin ageing, wrinkles and a higher risk of skin cancer. But what actually happens inside your skin cells when they are damaged by the sun’s rays?
That’s the question Gabriele Fontana – a postdoc at the Laboratory of Toxicology run by ETH professor
Shana Sturla
– sought to answer in his most recent research project. Fontana, who grew up near
Cremona in Italy, has been conducting research at ETH Zurich since 2019, but his fascination with the molecular world of cells began much earlier.
A flair for molecular biology
Fontana developed an interest in chemistry and biology while he was still at school. He has an extraordinary enthusiasm for scientific experimentation, yet it is not traditional biology, with its focus on botany and zoology, that quickens his pulse. Fontana’s real interest lies in the relatively young research field of molecular biology, which deals with the regulation and function of our genes and examines how genes interact with proteins. It’s here inside our cells where Fontana believes we will find the key to improving our understanding of diseases and our ability to develop effective drugs.
When he began his degree in biology in Milan in 2001, DNA analysis and sequencing were still laborious and expensive. Yet as his degree programme progressed, Fontana saw the process becoming quicker and easier, even for the sequencing of entire genomes. Excited by the potential opportunities of new genetic techniques, he was determined to experiment with them himself.
He stayed on at the University of Milano-Bicocca for his doctoral studies, in which he examined the molecular causes of amyotrophic lateral sclerosis (ALS), an incurable motor neuron disease. After completing his doctorate, he decided to take up a postdoctoral position at the Friedrich Miescher Institute for Biomedical Research in Basel.
A sticking plaster for DNA damage
By the time he was 30, Fontana was in Basel investigating how cells repair their damaged DNA. These mechanisms are crucial, since more severe damage can lead to malignant mutations that may ultimately cause cancer. “In the course of my work with colleagues at the Friedrich Miescher Institute, we discovered the key role of a protein called Rif1,” Fontana says. This protein acts as a kind of molecular “sticking plaster” for damaged DNA.
Fontana realised that this process takes place at very specific locations within the cell. “When a DNA strand is broken,” he says, “the damaged DNA is shunted to the edge of the nucleus, where the protein Rif1 is located, waiting to receive the broken DNA extremities and start the repair process.” When the ETH researcher observed this process under the microscope for the first time, he could hardly believe his eyes. It showed there was indeed a specific place in the cell – a kind of workshop with its own delivery service – where certain types of DNA damage are repaired. No one had ever demonstrated this quite so clearly.
