BioBeyond_NL

BioBeyond_NL: 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.

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Infrastructure and User Services  

BioBeyond_NL intends to establish an accessible, large-scale infrastructure merging mass spectrometry and glycoscience to enable researchers to unravel biological information beyond the genetic code, enabling the large-scale analysis of (bio)molecules, with the aim to elucidate their function in the context of their natural environment. BioBeyond_NL comprises three key cutting-edge infrastructural elements to provide a complete and integrated solution for (inter)national scientists to mine elusive biomolecular information:  

  • (Glyco)proteomics based on innovative mass spectrometry 
  • Spatial biology based on innovative mass spectrometry 
  • Glycochemistry for interactomics, glycomics, glycoproteomics, and spatial glycobiology 

These three synergistic innovations expand on and integrate existing LSRIs and European infrastructures, but require new and innovative investments in the foundational national mass spectrometry and glycoscience infrastructure, integrative AI, and a streamlined national access program to further extend the user base. 

Examples/description of the type of research  

The molecular complexity of life, which exceeds encoded information in genes or primary protein sequences and manifests in an astounding diversity of protein interactions and PTMs, has so far remained largely unelucidated. The BioBeyond_NL infrastructure will be developed with a strong focus on protein glycosylation as this is one of the most complex and prevalent PTMs affecting many protein–protein interactions (PPIs) and protein function. BioBeyond_NL provides instrumentation and corresponding tools and expertise to perform detailed studies of complex carbohydrates and glycoproteins at a single cell level. Mapping and quantifying PTMs, the biosynthesis of which is a dynamic, mutifactorial process, require significant technological advancements. Spatial glycobiology is virtually impossible to non-experts due to time-consuming experiments required to achieve sufficient molecular and spatial detail. Mass spectrometry (MS)-based molecular imaging allows the visualization of cellular glycotypes in complex tissue environments. The power of MS in cracking molecular complexity is boosted exponentially by integrating with chemical and computational tools. These tools, including glycan standards, glycan-targeting probes, databases, AI-based bioinformatic and software, are made available to BioBeyond_NL users.  

The BioBeyond_NL collaborative infrastructure will enable researchers to tackle these challenges together, through our consortium with established, world-leading expertise in:  

  1. Ultra-high sensitivity mass spectrometry glycomics and glycoproteomics;  
  2. MS-based molecular imaging to allow the visualization of cellular glycotypes in complex tissue environments; 
  3. Chemoenzymatic synthesis of carbohydrate standards and probes;  
  4. AI-based bioinformatics solutions for the complexity of these analyses.  

 How to access the infrastructure ? 

We distinguish 6 different access tiers based on 3 user categories: Academic, Technical Applied, and Educational. Academic access at additional operational cost to users from the consortium partners that are financially contributing to the operation of BioBeyond_NL, applied academic research and instrument development access. National and international academic users access infrastructure at operational cost, but no access fee; this policy falls in line with Article 5c of the European Charter for Access to Research Infrastructures. Technical Applied users aim at experimental development, to be assessed/approved by the technical desk after formal application. We estimate that ~10% of user time is of private category to prevent illegal government support of private institutions.

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