HS-SEQ is an ambitious multi-interdisciplinary European consortium (Grant agreement ID: 899687) that will tackle the technological bottleneck revolving around Heparan Sulfates (HS). HS plays key roles in health and disease, and has a tremendous potential for diverse biomedical applications. However, due to the unparalleled levels of structural complexity compared to other classes of biomolecules, we still do not fully understand how HS performs its functions, and how this can be fully exploited for therapeutic targeting. A major hurdle is a lack of methodologies for sequencing of heparin and HS, which will be addressed in this program.
This ambitious project is plausible as the investigators are leaders in their fields of research and have obtained critical preliminary data. The Boons group has already developed methodologies for the preparation of HS-oligosaccharides and a collection of compounds is available to develop separation and MS-IMS-IR based identification technologies, to define ligands for existing antibodies and for the development of new antibodies. The Turnbull group is a leader in the analytic chemistry and structure-function analysis of HS and has already developed a number of separation workflows an IM-MS methodology in collaboration with early career researcher Miller. The Pagel group has extensive expertise in developing IM-MS and cold-ion IR spectroscopy instrumentation for oligosaccharide analysis and has access to workshop infrastructure and a unique IR light source. The van Kuppevelt group has developed a number of phage display antibodies that are already widely used by the scientific community. The Arenas group has developed protocols for the differentiation of hPSCs into mDA neurons and in-vitro and animal models for Parkinson’s (PD) drug discovery using hPSCs and PD-iPS cells and isogenic controls. These cell-based systems will allow us to examine two options to exploit HS saccharides as novel therapeutic strategies for PD: cell replacement and drug development. The involvement of the industrial partners will ensure that the project will be informed by commercial imperatives and will result in transfer into applications beyond the research world.