From the scientific perspective, the research group is focused in exploring molecular recognition events from the chemical perspective, mostly in unravelling the molecular basis of the recognition of glycans by receptors in solution.
The group employs a multidisciplinary approach, using the synergic combination of organic synthesis, protein biochemistry and molecular biology, biophysics, molecular modeling, and NMR, using a wide network of collaborations with specialists worldwide.
Major contributions in the field include our systematic studies on the interactions of glycans with specific lectins (the 1st reported NMR structure of a glycan/lectin complex was achieved in his lab in 1995). Such detailed investigations have contributed significantly to our global understanding of glycan-mediated interactions in health and disease, including infectious and inflammatory processes. These studies conducted to the 2010 International Whistler Award in Carbohydrate Chemistry, following the Bruker award of the NMR division of RSEQ (2008) and the Janssen-Cilag award of RSEQ (2003).
The group does not only apply, but also develop, NMR methods for studying the structural and dynamic properties of ligands and their interaction with relevant proteins. Particularly, the fine chemical details of the interactions between sugars and proteins have been explored, with special emphasis on the relative role of sugar-aromatic stacking forces in the recognition process. The origin and relative importance of the forces that mediate these interactions are still under study and are a key part of the research in the group. Recent advances in our research are focused on disentangling how receptors recognise a given epitope in complex N-glycans, which present multiple epitopes. This has lead to the use of a precise NMR methodology, even using living cells, assisted by molecular dynamics and biophysical and structural biology methods, including X-ray crystallography. Recent methodology developments have permitted to use paramagnetic metals (lanthanides) to unravel hidden conformational features of N-glycans and to detect their molecular recognition events. The use of lanthanides is complementary to the employment and generation of other chemical novel NMR-sensitive tags, especially those based on 19F nuclei. The expansion, exploitation, and generalization of these novel concepts is generating a breakthrough in the field, with huge possibilities in the molecular recognition arena, permitting the access to the detailed study of the interactions of large and complex glycans, which were previously inaccessible to the study by NMR or other means, due to their intrinsic flexibility.
Key projects of the group involve detailed multidisciplinary investigations on galectins and C-type lectins, under the guidance of Dr. Ana Ardá (Ramón y Cajal fellow), as well as on siglecs, a novel research topic for the group, under the supervision of Dr. June Ereño-Orbea (Ikerbasque Research Fellow). The different members of the group enjoy from different collaborations throughout the world, including Europe, North America, South America, Australia, and Asia. Besides the funding from AEI, the group is currently funded by the EC (ERC AdG 2018 RECGLYCANMR to J. Jimenez-Barbero, ITN 2019 BactiVAX to J Jimenez-Barbero, and ITN 2020 Glytunes to J. Ereño-Orbea). Research collaborations and contracts with different companies within the Basque Country, Spain, and other countries in Europe also provide added value to our investigations.
Life & Medical Sciences
- Biosciences & Health
- Molecular recognition events from the chemical perspective