Projektbeschreibung
Neue Instrumente zur Sequenzierung von Heparansulfatstrukturen
Heparansulfat (HS) ist ein Polysaccharid, das in Tiergeweben vorkommt. HS bindet an verschiedene Proteinliganden und reguliert eine Reihe von biologischen Aktivitäten, darunter Entwicklungsprozesse, die Angiogenese, die Blutgerinnung sowie die Tumormetastasierung. Um dem bisherigen Mangel an adäquaten Methoden zur Sequenzierung von HS-Strukturen zu begegnen, zielt das EU-finanzierte Projekt HS-SEQ darauf ab, ein neues Instrument zu entwickeln, das mehrere Verfahren und Aufgaben vereint: die Massenspektrometrie zur Aufzeichnung diverser molekularer Eigenschaften, wie z. B. dem Molekulargewicht; die Ionenmobilitätsspektrometrie zur Aufzeichnung von Stoßquerschnitten; und die Gasphasen-Infrarot-Ionenspektroskopie zur Aufzeichnung der Schwingungseigenschaften. Diese neue Technologie wird die Identifikation von HS-Codes ermöglichen, welche die Produktion von dopaminergen Neuronen aus menschlichen pluripotenten Stammzellen für die Zellersatztherapie bei Parkinson fördern können.
Ziel
Heparin and heparan sulphate (HS) are highly sulfated polysaccharides that reside on the cell surface and extracellular matrix of all mammalian cell types. Understanding their functions has tremendous potential to unlock the next generation of heparin-based diagnostics and therapeutics for multiple diseases including inflammatory and neurological diseases, cancer, and wound healing. Despite this promise, it is very difficult to harness this biomedical potential due to a fundamental technology bottleneck - lack of methods for the sequencing of HS structures to define the natural “HS codes” that underpin many biological functions. HS-SEQ will address this hurdle and will place Europe in the leading position in the emerging field of glycomics of heparin and HS. It is our vision that robust sequencing methods for heparin and HS will only be possible when new instrumentation will be developed that can simultaneously record multiple molecular properties such as molecular weight by mass spectrometry (MS), collisional cross sections (CCS) by ion mobility spectroscopy (IMS) and vibrational properties by gas-phase infra-red (IR) ion spectroscopy. To implement such a platform, large collections of well-defined HS saccharide standards are needed to generate reference databases that can match molecular properties to structural features. To obtain the required collection of HS saccharides, HS-SEQ will develop and implement an automated platform for chemoenzymatic synthesis of such compounds. The synthetic HS saccharides will also provide unique opportunities to develop an antibody toolkit to identify epitopes expressed by cells/tissues. Specific transformational applications of the new technology will be pursued: (i) identify HS codes that promote the generation of dopaminergic neurons from human pluripotent stem cells (hPSCs) for cell replacement therapy in Parkinson’s disease; and (ii) achieve unprecedented in-depth analysis of pharmaceutical and next-generation heparins.
Wissenschaftliches Gebiet
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicineneurologyparkinson
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- natural sciencesphysical sciencesopticsspectroscopy
Schlüsselbegriffe
Programm/Programme
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenUnterauftrag
H2020-FETOPEN-2018-2019-2020-01
Finanzierungsplan
RIA - Research and Innovation actionKoordinator
3584 CS Utrecht
Niederlande