FNP First TEAM/2016-1/2

Living organisms, including humans, require so called enzymes to carry out all essential cellular functions needed for survival, reproduction and adaptation to changing environmental conditions. The blueprints for the production of these specialized cellular machines are encoded in the genomic deoxyribonucleic acid (DNA) of each individual cell in our body. Cells use information stored in DNA to (i) produce messenger ribonucleic acid (mRNA) molecules and (ii) employ transfer RNA (tRNA) molecules to translate these mRNAs into correctly assembled chains of amino acids. Once these chains are produced correctly, they fold into their three dimensional structure that allows them to carry out their specialized function. The structure is different for every protein, it depends on the sequence of the incorporated amino acids and it is adapted to the respective enzymatic activities. In this FirstTEAM project we are interested in understanding the molecular details of specific tRNA modification reactions leading to the addition of small chemical groups. These subtle changes have strong influence on the correct production of properly folded and active enzymes. In detail, our aim is to uncover the structure, organization and regulation of molecular machineries that conduct these modification reactions and characterize their activity. Strikingly, patients suffering from certain types of cancer and neurodegenerative diseases often carry mutations in the proteins that are components of these complexes. Therefore, it is of prime scientific and clinical importance to study these evolutionary highly conserved mechanisms. Our work will not only clarify their role in normal healthy cells, but is also necessary to understand their contribution during the onset of various diseases.