The new study shows that intestinal bacteria can affect the molecular type of glycoslation – the presence of sugar groups on proteins – within the brain. Loan: Daniela Velasco Lozano/EMBL
Our guts are home to billion bacteria, and research has shown how crucial for our physiology in the previous few a long time – in health and illness. The new study conducted by EMBL Heidelberg researchers shows that intestinal bacteria could cause deep molecular changes in considered one of our most significant organs – the brain.
The new study, published within the journal Nature Structural and Molecular Biology, was the primary to point out that bacteria living within the intestines can affect how proteins within the brain are modified by carbohydrates – a process called glycoslation. The study was possible because of the new method developed by scientists – DQglyco – which allows them to look at glycoslation on a much higher scale and resolution than previous studies.
A new option to measure glycoslation
Proteins are the works of our cells and their foremost constructing elements. On the opposite hand, sugars or carbohydrates belong to the foremost sources of the body’s energy. However, the cell also uses sugars for chemical protein modification, changing their functions. This is named glycoslation.
“Glycoslation can affect how the cells join each other (adhesion), the way of moving (mobility), and even how they talk to each other (communication)”, explained Clément Potel, the primary creator of the study and scientist of the Savit team. “He is involved in the pathogenesis of several diseases, including cancer and neuron disorders.”
However, glycoslation was traditionally extremely difficult to look at. Only a small a part of the protein within the cell is glycoslated and concentrates enough within the test sample (a process called “enrichment”) is generally laborious, expensive and time -consuming.
“So far, it has not been possible to conduct such research on a systematic scale, in a quantitative manner and with high playback,” said Michail Savitski, team leader, senior scientist and head of Proteomics Core Facility at Embl Heidelberg. “These are challenges that we managed to overcome the new method.”
DQglyco uses easily accessible and low-cost laboratory materials, similar to functionalized silica pearls, to selectively enrich glycosilized proteins from biological samples, which might then be thoroughly identified and measured. By using a technique for mouse brain tissue samples, scientists can discover over 150,000 glycosilized types of protein (“proteofform”), which is a rise in greater than 25 times in comparison with previous studies.
The quantitative nature of the new method signifies that scientists can compare and measure the differences between samples from different tissues, cell lines, species, etc. It also allows them to look at the pattern “microheterogenicity” – a phenomenon wherein the identical a part of protein will be modified by many (sometimes lots of) different groups of sugar.
One of probably the most common examples of microheterogenicity are human blood groups, wherein the presence of various sugar groups on proteins in red blood cells determines the style of blood (A, B, O and AB). This plays the foremost role in deciding on the success of blood transfusion from one person to a different.
The new method allowed the team to discover such microheterogenicity in lots of of protein places. “I think that the widespread spread of microheterogenicity is something that people always assumed, but this has never been clearly demonstrated, because you need to have sufficient coverage of glycosilized proteins to be able to speak,” said Mira Burtscher, the following first creator of the study and a PhD student from Savitski.
From intestinal to brain
Given the precision and power of the tactic, scientists decided to make use of it to unravel an impressive biological query. In cooperation with the Michael Zimmermann group in EMBL, they tested whether the intestinal microbiome had any impact on the glycoslation signatures that they observed within the brain. Both Zimmermann and Savitski are a part of the transverse motif of microorganism ecosystems within the EMBL, which was introduced by the EMBL 2022-26 EMBL molecules.
“It is known that intestinal microbiome can affect nerve functions, but molecular details are largely unknown,” said Potel. “Glycoslation is involved in many processes, such as neurotransmission and conducting axons, so we wanted to see if it was a mechanism with which intestinal bacteria influenced the molecular routes in the brain.”
Interestingly, the band stated that in comparison with “mice without germs” mice grown in a sterile environment, in order that they completely lack microorganisms of their body, mice colonized with various intestinal bacteria had different glycosal patterns within the brain. The modified patterns were particularly visible in proteins, that are known to be essential in nerve functions, similar to cognitive processing and axon growth.
Data data sets are openly available through a new dedicated application for other researchers. In addition, the team can also be curious whether the info will be used to tell forecasts regarding glycoslation places, especially in numerous species. To this end, they use approaches to machine learning, similar to Alphafold-Naroloca-based AI to predict protein structures recognized by the Nobel Prize in the sector of chemistry 2024.
“I trained mouse data models, we can start predicting what can be, for example, the variability of glycoslation places in humans,” said Martin Garrido, Postdoc in Savitski and Saez-Rodriguez groups in EMBL and one other first creator of the study. “This can be very useful for people examining other organisms to help them identify glycoslation places in their interesting proteins.”
Scientists are also working on the usage of a new approach to answering more basic biological questions and understand the functional role of glycoslation in cells.
About the European Molecular Biology Laboratory
The European Molecular Biology Laboratory (EMBL) is a European Laboratory of Natural Sciences. We provide leadership and coordination of natural sciences throughout Europe, and our world -class fundamental research is searching for common and interdisciplinary solutions for a number of the biggest challenges of society. We provide training for college students and scientists, we drive the event of new technologies and methods in natural sciences and offer the most recent research infrastructure for a large experimental and data range.
EMBL is an intergovernmental organization with 29 Member States, one associate member and one potential member. In our six places in Barcelona, Grenoble, Hamburg, Heidelberg, Hinxton near Cambridge and Rome, we try to raised understand life in its natural context, from molecules to ecosystems.
