Project description
Imaging glycoconjugates one molecule at a time
All cells are covered with a thick shell of carbohydrates (a.k.a glycans) – which, like ID cards, help identify the cell (eg. bacteria or human cells) and its state (eg. healthy or cancerous). Understanding structures of these glycans is key to new diagnostics and therapeutics for many health challenges today. However, structural analysis of these glycans is challenging as they are found attached to proteins and lipids. The resulting complexity and diversity of these "glycoconjugate" molecules pose difficulties to our present ensemble-averaged analytical methods. The ERC-funded GlycoX project aims to reveal molecular structures of glycoconjugates at single-molecule level by imaging them one by one. To accomplish this, glycoconjugate ions are soft landed on a surface and imaged individually by scanning tunnelling microscopy.
Objective
GlycoX aims to develop single molecule analytical methods to address the challenge of elucidating glycoconjugate structures. Glycoconjugates are glycans (a.k.a carbohydrates) that are attached to another biomolecules such as proteins or lipids. Glycoconjugates are essential to all living organisms, carrying out key cell-cell communication roles in immune system or in microbial infection. Glycoconjugates are found in all biological systems and yet, when compared to proteins or nucleotides, very little is known about their structures and how they lead to their biochemical properties or how they can be exploited in therapeutics. Efforts to reveal their structures by ensemble averaged approaches, whether primary structures (sequences) or secondary structures (conformations), have been severely hampered by the high complexity and flexibility of glycans.
GlycoX addresses this challenge by direct imaging of single glycoconjugate molecules, devoid of any ensemble averaging. To this end, glycoconjugate ions generated from electrospray ionization are soft landed on surface and imaged one-at-a-time by scanning probe microscopy in vacuo. The Project proposes the use of direct imaging (1) to identify the glycoforms of any glycoconjugates (i.e. variants of a specific glyconjugate that possess different glycan primary structures), (2) to sequence any glycan residues in any glycoconjugates, and (3) to determine the conformations of any glycoconjugates. The Project plans to focus on glycoconjugates that are intractable by present analytical methods, many of which are central in immune system, in microbial infection, and in emerging diagnostics, drugs, and vaccines. These works have far reaching impacts: shedding light into the language used by cells to communicate and by pathogens to infect; creating new opportunities in glycan-based therapeutics; as well as opening new frontiers in single molecule analytical chemistry of biomolecules.
Fields of science
- natural scienceschemical sciencesanalytical chemistry
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
- natural sciencesphysical sciencesopticsmicroscopyscanning tunneling microscopy
- natural scienceschemical sciencesphysical chemistry
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
ERC - Support for frontier research (ERC)Host institution
80539 Munchen
Germany