Infrastructure to Unravel Molecular Complexity Beyond the Genetic Code

The understanding of cellular biological processes, which lie at the basis of human health and disease, but also animal, microbial, and plant biology, requires the realization of a research infrastructure that allows the in-depth investigation of this complex biology beyond the genome. BioBeyond_NL is an accessible, large-scale national infrastructure that provides combined access to cutting-edge mass spectrometry, spatial biology, and glycoscience to enable researchers to unravel biological information beyond the genetic code. Through its solid foundation and future-proof innovation, BioBeyond_NL aims to be a sustainable, (inter)national research infrastructure enabling continuous scientific breakthroughs in biomedicine.

The BioBeyond_NL infrastructure will enable researchers to tackle the next challenge in molecular life sciences, unraveling and understanding biology that extends beyond the genetic code. Although the genome is at the central dogma of biology, it only defines the beginning of life’s complexity. That complexity is defined by the interplay of a plethora of biomolecules in the cascade of synthesis and transformation beyond the genome. The proteins, glycans, lipids, and metabolites downstream of the genetic code regulate the majority of all biological processes. This complexity beyond the genetic code is convolved with external factors, such as environmental and lifestyle influences, that can affect post-translational protein modifications (PTMs), molecular and cellular interactions, immune function, and metabolism. Elucidating the importance of glycans, in a field of science called glycoscience, would revolutionize disease diagnosis and treatment, yet it remains largely uncracked. Central to BioBeyond_NL is mass spectrometry (MS), an analytical methodology that enables researchers to perform large-scale analysis of (bio)molecules to acquire detailed insight into many non-genetically–encoded interactions and modifications. BioBeyond_NL proposes to establish an accessible, large-scale national infrastructure merging mass spectrometry and glycoscience to enable researchers to investigate these (bio)molecules and to elucidate their function in the context of their natural environment, in greater molecular, spatial, and temporal detail.

BioBeyond_NL comprises three key state-of-the-art infrastructural elements to provide a complete and integrated solution for (inter)national scientists to mine elusive biomolecular information: mass spectrometry technologies for (glyco)proteomics; mass spectrometry technologies for spatial biology; glycoscience technologies for interactomics, glycomics, glycoproteomics, and spatial glycobiology. These three synergistic innovations are spearheaded by Dutch experts in proteomics, MS imaging, and glycobiology who have exceptional track records in research and have provided access to their infrastructures in the Netherlands and Europe for over 15 years. They will expand on and integrate existing LSRIs and European infrastructures, but with new and innovative investments in the foundational national mass spectrometry and glycochemistry infrastructure. BioBeyond_NL aims to invest in innovative infrastructure for single-cell– and single-molecule–based, high-throughput MS and MS-based molecular imaging, augmented with novel chemical probes that target the detailed visualization and modification of glycan complexity in a spatial context as well as labeling workflows for complex, targeted analyses. Underlining and supporting these infrastructures are integrative artificial intelligence (AI) to enable smart experimentation and data analysis and a streamlined national access program to ensure a broad user base. Through its solid foundation and future-proof innovation/planning, BioBeyond_NL aims to be a sustainable, (inter)national infrastructure enabling researchers in fundamental and applied biomedical scientists to elucidate the vast, complex biology beyond the genome-knowledge key to make breakthroughs in biomedicine and biology.