Inspiring and productive meeting with a day-long program of research talks and a joint lunch of Jimenez-Barbero, Reichardt, Guerin, Fernandez-Tejada and Anguita/Prados groups with special guest Manuel Martin-Lomas. More to come!
CarboMet is a Coordination and Support action within the FET-OPEN Horizon 2020 funding schemeand coordinated by the University of Manchester (Prof. Sabine Flitsch) in which Asparia Glycomics a spin-off from our group is participating alongside a number of other stakeholders from industry and academia active in glycoscience research. CarboMet will foster and drive collaboration, cross-fertilisation and communication among stakeholders to facilitate a uniform approach to the metrology and/or measurement of carbohydrates for exploitation in biopharmaceuticals, diagnosis of disease and precision medicine, food and personal care and sustainable material BioIndustries. This will be achieved through a consolidated approach towards the modification of key emerging technologies or identification of radically new technologies currently unforeseen by technology roadmaps.
Carbohydrates and glycoconjugates are especially challenging to analyse due to their high stereochemical diversity which means it is difficult to distinguish between them and fully characterise using standard techniques and methods. Current methodologies to fully solve 3-D structures include NMR and X-Ray Crystallography which are low-throughput, require large samples and have poor sensitivity. Emerging technologies are beginning to address these issues such as Ion Mobility Mass Spectrometry (IM-MS) and the combination of 3 gas phase techniques: IR spectroscopy with IM-MS in-vitro enabling high-throughput with higher sensitivity, small samples, and analysis from mixtures to provide structural detail on each component. These technologies are underpinned by advanced supporting technologies such as automated carbohydrate synthesis, bioinformatics tools and databases, and new suites of enzymes for glycan synthesis and modification. CarboMet will use a range of communication and dissemination tools (meetings, workshops, website, surveys, briefing papers) to engage key stakeholders, to establish the current emerging technologies, limitations, and barriers to implementation. Priority areas, future challenges and a wish list of capabilities will then be defined, culminating in the production of a roadmap for 2030, setting out a Europe-wide vision. These capabilities will lead to new robust metrologies for the exploitation of carbohydrates.
Together with the groups of Jesus Jimenez-Barbero, CIC bioGUNE, Bilbao, Antonio Franconetti, University of Seville, and Javier Cañada, CIB-CSIC, Madrid we have just published a study in the journal Chemistry, A European Journal titled Fluoroacetamide Moieties as NMR Probes for molecular recognition of GlcNAc-containing sugars: Modulation of the CH-π Stacking Interactions by Different Fluorination Patterns. In the paper we propose the use of the fluoroacetamide and difluoroacetamide moieties as sensitive tags for detecting sugar-protein interactions by simple 1H and/or 19F NMR methods. As selected process, we have chosen the binding of N,N’-diacetyl chitobiose, a ubiquitous disaccharide fragment in glycoproteins, by wheat germ agglutinin (WGA), a model lectin. Using STD-NMR, we experimentally demonstrate that, under solution conditions, the molecule containing the CHF2-CO-NH- moiety is the stronger aromatic binder, followed by the analogue with the CH2F-CO-NH- group and the natural molecule (with the CH3-CO-NH- fragment). In contrast, the molecule with the CF3-CO-NH- isoster displays the weakest intermolecular interaction (one order of magnitude weaker). Since sugar-aromatic CH-π interactions are at the origin of these observations, these results further contribute to the characterization and exploration of these forces and offer an opportunity to use them to unravel complex recognition processes.
CIC biomaGUNE and private investors have come together to set up Asparia Glycomics, a company specialized in the production and marketing of reagents, reference standards, kits and software for glycan analysis in clinical diagnosis and for quality control of biopharmaceuticals.
The new company is commercializing state of the art technology developed in our laboratory during the last 5 years to quantify protein glycosylation with higher precision and higher throughput than existing solutions. Asparia Glycomics is offering unique stable isotope labeled glycans as internal standards, custom made quantification software and reagents for glycan analysis by mass spectrometry.
The company is led by Dr. Juan Echevarria, a co-developer of the technology, who moved to Asparia Glycmics from the glycotechnology laboratory. The standards and kit solutions offered by Asparia Glycomics find multiple applications in clinical glycomics research, biopharmaceutical glycan analysis and glycobiology in general. For more information visit https://aspariaglycomics.com/
After a first publication of the synthesis and microarray binding analysis of xylosylated N-glycans we have just published a second paper in ACS Chemical Biology describing the effect of core xylosylation on carbohydrate based dendritic cell targeting.
Abstract: Targeting antigens to dendritic cell subsets is a promising strategy to enhance the efficacy of vaccines. C-type lectin receptors (CLRs) expressed by dendritic cells are particularly attractive candidates since CLR engagement may promote cell uptake and may further stimulate antigen presentation and subsequent T cell activation. While most previous approaches have involved antibody-mediated CLR-targeting, glycan-based CLR targeting has become more and more attractive in recent years. In the present study, we show that small structural glycan modifications may markedly influence CLR recognition, dendritic cell targeting, and subsequent T cell activation. A biantennary N-glycan (G0) and its analogous O-2 core xylosylated N-glycan (XG0) were synthesized, covalently conjugated to the model antigen ovalbumin, and analyzed for binding to a set of murine CLR-Fc fusion proteins using lectin microarray. To evaluate whether the differential binding of G0 and XG0 to CLRs impacted dendritic cell targeting, uptake studies using murine dendritic cells were performed. Finally, effects of the ovalbumin glycoconjugates on T cell activation were measured in a dendritic cell/T cell cocultivation assay. Our results highlight the utility of glycan-based dendritic cell targeting and demonstrate that small structural differences may have a major impact on dendritic cell targeting efficacy.
Laure Medve together with her tutor Sonia Serna (in the back)
Immunoshape fellow Laura Medve from the lab of Prof. Anna Bernardi, University of Milan is visiting our lab for a 2 month secondment to explore the interaction of novel glycomimetics with C-type lectin receptors employing microarray screening technology.
At a recent biannual meeting of the Organic Chemistry Divison of the Spanish Royal Society of Chemistry at Punta Umbria, Spain, Glycotechnology Group PI Niels Reichardt had the opportunity to give an update of our current research covering Synthesis and Biomedical Applications of Parasite Glycans in front of over 320 delegates. The invited lecture covered strategies for the preparation of complex and asymmetrical N-glycans and described their potential as vaccine leads against parasite infections or as immunomodulatory agents in the treatment of autoimmune diseases. The development of biomedical applications is being carried out in close collaborations with groups in Germany, the UK and The Netherlands.
On June 8th Prof. Antoni Planas from the Department of Biotechnology at the Institut Quimic Sarría at the the University Ramon Llull in Barcelona visited our institute and the glycotechnology group to present his recent groundbreaking work on the “Specificity of chitin deacetylases: structural determinants defining the de-N-acetylation pattern” in a very well-received seminar. Options for collaborations with our group in the development of a useful high-throughput assay were discussed. Posing for the photographer right after lunch are from left to right Manuel-Martin Lomas, Antoni Planas, Niels Reichardt and Jordi LLop.
After 4 years of hard work and a broad training in multiple techniques from chemistry and biology Kasia succesfully defended her PhD titled Chemoenzymatic Synthesis and Immunological studies of Xylosylated N-glycans on the 7th of June at the University of the Basque Country in San Sebastian. Congratulations and all the best for your postdoc in London! Here a foto of freshly baked Dr. Brzezicka with the jury (from left to right) Toni Planas, Ron Hokke, special guest Manuel Martin-Lomas and Jesus Jimenez-Barbero after the defense waiting for lunch.
A few days ago, on the 18th of May we had a visit from Juan-Ma Falcón, a research group leader and Ikerbasque professor from close-by CICbioGUNE research center in Bilbao to give a talk titled “Exosomes: metabolic nano-machines encoding complex signals”. Juan-Ma is a long-standing collaborator of our group and we are jointly exploring the effect of glycosylation on exosome targeting employing lectin arrays and different approaches for engineering exosome glycosylation. In his seminar Juan-Ma highlighted exosomes as our bodies own nanotechnology approach for the tissue specific delivery of metabolites, RNA and proteins from a source cell. We were so busy discussing science that we forgot to take a picture during his visit. Here is an archive foto of Juan Falcón.