Cancer research could soon benefit from a new technology allowing investigation of how the DNA interacts with the proteins. Recent advances in tackling the disease stem from a change in our view of the genome—all the genes contained in our DNA. Scientists now understand that instead of just carrying the genes as a static code, it is now known that the DNA chains also interact with proteins, forming bonds. These proteins control the way the genes work. However, the current methods for investigating how the DNA interacts with the proteins are based on binding proteins chemically to DNA and then by gene sequencing, finding out the DNA binding sites of these the proteins.
The trouble is that chemically binding of proteins is slow, several minutes, which does not allow the investigation of the dynamics of this process at short time scales. Now, a research group at the University of Naples, Italy, led by Lucia Altucci, associate professor in biomedical research specialised in cancer and based at the Second University of Naples, in Italy, has developed a laser technology creating the bonds between proteins and DNA with extremely short pulses. Altucci is also the project coordinator of the EU-funded research project ATLAS, which aims to develop this technology for studyinghow the genome works.
How will your research ultimately contribute to cancer research?
Cancer is a disease of the DNA, caused by alterations of the genome, but also by alterations that are related to so-called epigenetic mechanisms. There is certainly a cross-talk between the genome and the epigenome.
How would you define epigenetics?
Epigenetics contains the Greek epi, which means "over." So "over genetics" refers to a regulation of the genome, a so-called functional way, to read the genome. Just like in a tape recorder, there are proteins that can write to the DNA, placing markers. There are also proteins that can read these markers, and others which can erase these markers. These mechanisms can activate, silence, or modify functions in the expression of a gene.
Specifically, we believe that we will be able to reclassify the role of some so-called transcription factors, which are proteins that control the turning on or off of genes, and the role of some enhancers, which are proteins that bind another protein to the DNA. There are some proteins that have been classified as transcription factors because they can bind directly to DNA, but we do not know if they are really doing it or not.
Lasers have been used to study DNA for several years. In what way is your approach new?
The idea to use lasers on DNA is an old idea. The idea to use femtosecond lasers is quite new and comes from discussions with a physicist, who actually is my brother. So the idea to test this and set up a new technology became the basis of the ATLAS project.
How does this technology inform us better on about how the genome works?
The innovative aspect is that this way you can study dynamic processes at time scales lower than what is currently possible. In times shorter than a second, you can study the binding of DNA to proteins. In particular, you can study the direct versus indirect bindings in a dynamic way. In indirect bindings, a protein links to DNA via one or more so-called adaptors, which are also proteins. As far as I know, this cannot be done with alternative technologies because of a bottleneck of five minutes. We can check for transitory bindings of proteins that last less than one minute.
Image credits: La Repubblica