Post-translational modifications (PTMs) act as key cellular signals that are involved in virtually all processes that govern the fate of cells and organisms. By altering the chemical state of proteins dynamically, they not only enormously expand the functional repertoire of the proteome but also do it in a time-dependent manner as part of a biological system’s response to its environment. PTMs come in different varieties, ranging from small chemical moieties, such as phosphorylation and acetylation, to entire proteins like ubiquitin, and extending to the attachment of nucleotides. Nucleotide-based post-translational modifications (nbPTMs) play key roles in health and disease, from bacterial pathogenesis to cancer. The study of nbPTMs has far-reaching implications for society, particularly in healthcare and medical research. Understanding nbPTMs is pivotal in comprehending the molecular basis of various diseases and developing novel therapeutic strategies and diagnostic tools. However, technical challenges of these versatile, but chemically complex protein modifications have constrained our fundamental understanding of even the most intensely studied nbPTMs, including ADP-ribosylation (ADPr) and AMPylation, for decades.
The overarching aim of the EU-funded project ‘nbPTMs’ is to establish, apply and disseminate a methodology to transform the study of nbPTMs. A key goal is generating nbPTM-specific recombinant antibodies by converting our basic discoveries of Serine ADPr by the writer complex HPF1/PARP1 into a technology for preparing challenging peptide antigens. By combining these novel tools with unambiguous and unbiased mass spectrometry-based proteomics, the project aims to detect known nbPTMs with unprecedented sensitivity and specificity, as well as unveil novel forms of nbPTMs. Particularly intriguing and significant nbPTMs will be selected for extensive biological characterization. The resulting tools, materials, methods, discoveries and proteomic datasets will be made publicly available, enabling investigations of nbPTMs by the scientific community.
As a project at the intersection of biology, chemistry, and technology, 'nbPTMs' is uniquely poised to make significant contributions to biomedical research. By integrating state-of-the-art technological advances with biological inquiries, the project is expected to yield fundamental biological insights and tools that could transform our approach to disease treatment and diagnosis.
