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Do you speak DNA?

Scientists are trying to decipher the language hidden in our bodies

Yes, DNA has its own language and scientists want to understand it to apply personalized therapeutic solutions based on the analysis of the individual's genomic biomarkers and their regulation. What are we talking about? A group of researchers under the flag of the MRG-GRammar (Massive Reverse Genomics to Decipher Gene Regulatory Grammar) project, a European funded project under Future and Emerging Technologies in Horizon 2020, are committed to understanding the language of DNA, combining synthetic biology with innovative DNA-printing technologies and bioinformatics. Understanding this language will be useful to implement a healthcare system tailored to the needs of each person, for the detection of different types of cancer, like melanoma for example, and more generally for finding the origin of many diseases. As for any other language, the language of DNA is composed of an alphabet and grammar. Four letters (base pairs) make up the genetic alphabet: A, T, G, C; and a gene is nothing more than a word, that is a sequence of those letters like TCGATTAGG... When the Human Genome Project finished in 2003, scientists had determined the nucleotide base-pairing sequence in the DNA of Homo sapiens. It gave us a book to read, but although we can read the letters and recognize many words of its vocabulary, we do not know enough grammar rules to be able to grasp the meaning of the whole book. In order to manage such complexity, the researchers of the MRG-GRammar project have narrowed down their interests, focusing on the rules regulating gene expression, the final proteins made by DNA. Indeed, the regulatory activity of the genome, which determines how genes are expressed, is essential to understand what kind of consequences a mutation could bring in the genomic regulatory regions, for example a melanoma cancer. Beyond healthcare, these understanding gene regulation could be used for better biofuel production, in agriculture and in other industrial fields. “If we were able to understand what goes wrong and why, for instance with cells, by capturing and then mutating the rules that instruct them to react in a given way, this would be an incredible step ahead for medicine”, says Sarah Goldberg, researcher at the Technion – Israel Institute of Technology in Haifa, one of the scientists involved in the project. In particular the strategy followed by the project members consists of generating new types of biological datasets that systematically explore all possible regulatory combinations building a knowledge base from which the regulatory algorithm can be derived. Starting from that algorithm it could be possible to not only decipher extant natural regulatory code, but also interpret variations leading to a profoundly deeper understanding of the origins of many diseases. Promising progress was documented by a publication in Nature Communications. The MRG-Grammar team has also collaborated with artist Anna Dumitriu in the framework of FEAT, a FET project exploring art as a new channel to communicate science. The outcome of the collaboration is Dumitiu's artwork "Make Do and Mend", which the artist realised by editing the genome of an E. coli bacterium with the revolutionary technique CRISPR. The goal of this effort is to raise awareness of the resistance to antibiotics developed by bacteria, one of the major challenges faced by modern medicine. The €4M MRG-GRammar project involved seven partners and is coordinated by Technion – Israel Institute of Technology in Haifa, Israel.