Beyond DNA: NWO invests in infrastructure to study sugar-modified proteins in cells

BioBeyond_NL, a collaboration between researchers from Maastricht University, Utrecht University, Leiden University Medical Center, and Radboud University Medical Center, will receive funding in the coming years through NWO’s National Roadmap for Large-Scale Research Infrastructure (LSRI). The total grant amounts to seventeen million euros, with more than half allocated to Utrecht. The funding will support the creation of a national infrastructure aimed at advancing the understanding of the structure and function of proteins and sugars in their natural environment.

Proteins can be thought of as machines within our cells that perform a wide range of tasks. Their blueprints are stored in our DNA as a genetic code. Each segment of DNA that provides the instructions for a specific hereditary trait is known as a gene.

Nowadays, it is relatively easy to read the DNA code, and with it, the genes that encode proteins. But the DNA sequence is only part of the story. We now know that a single gene can give rise to hundreds of different proteins, each with its own unique structure and function. Moreover, these proteins interact not only with one another but also with DNA, RNA, lipids, and sugars.

Glycosylation has a major impact on how proteins function. However, compared to our understanding of DNA and proteins, our knowledge of protein glycosylation is still in its early stages.

Glycosylation

Within BioBeyond_NL, the focus is primarily on how sugars influence proteins, explains Utrecht University professor Albert Heck. “When sugar molecules bind to proteins, we call this the glycosylation of those proteins. Glycosylation has a major impact on how proteins function. However, compared to our understanding of DNA and proteins, our knowledge of protein glycosylation is still in its early stages. This is largely because we do not yet have the technologies needed to study it on a large scale. BioBeyond_NL is going to change that.”

A better understanding of protein glycosylation offers insights into disease mechanisms and helps improve therapeutic medicines. “Many therapeutic drugs, such as antibodies commonly used to treat cancer and rheumatism, are glycosylated,” explains Heck. “And because human receptors, the proteins found on the surface of cells, have very specific glycosylation patterns, bird flu cannot (yet) jump from birds to humans. These are just two examples of how crucial protein glycosylation is.”

Biologists, chemists, data analysts, and AI experts are joining forces to gain a deeper understanding of how the cells in our bodies function.

Collaboration

The main applicant for BioBeyond_NL is prof. dr. Ron Heeren of Maastricht University. Within Utrecht University, the project brings together researchers from a wide range of disciplines, as researchers from the departments of Pharmaceutical Sciences, Information and Computing Science, Biology and Chemistry are involved. Alongside Heck, the Utrecht team includes dr. Kelly Stecker, prof. dr. Geert-Jan Boons, dr. Jack Li, prof. dr.  Sanne Abeln, and dr. Pavel Sinitcyn.

“Biologists, chemists, data analysts, and AI experts are joining forces to gain a deeper understanding of how the cells in our bodies function,” Heck explains. “Using mass spectrometry, a technique that allows us to determine the mass of molecules, we will generate and analyze large datasets on proteins and their interactions with other molecules.” A substantial part of the funding will be used to acquire new research instruments to make this work possible.