PLATELET RECEPTORS (334260)

  https://cordis.europa.eu/project/id/334260

  FP7 (2007-2013)

  Characterizing Regulatory Principles in Platelet Surface Receptors Via X-ray Crystallography and Small-molecule Design

  Marie-Curie Action: "Career Integration Grants" (FP7-PEOPLE-2012-CIG)

  drug discovery  ·  vascular diseases  ·  crystallography  ·  immunology  ·  oncology

  2013-03-01 Start Date (YY-MM-DD)

  2017-02-28 End Date (YY-MM-DD)

  € 100,000 Total Cost

  Description

Signaling via platelet surface receptors is essential for maintaining hemostasis and thrombosis, and plays key roles in pathophysiological processes related to development, immune responses and cancer. Despite their vital roles, important aspects of their regulation mechanisms remain unknown due to inherent flexibility and multilayered activation. I propose to embark upon a new approach to investigate the dynamical processes by which platelet receptors are regulated using a combination of x-ray crystallography, electron microscopy, biochemistry, bioinformatics and small-molecule design. My goal is to decipher the atomic mechanistic details of the relationship between ligand-binding, dynamics, activation and transduction of signals in platelet receptors, which would facilitate the development of accurate interventions with their cellular processes, namely drugs that will target a range of cardiovascular conditions. My working hypothesis is that small molecules that act as allosteric regulators can uncover new principles in the regulation mechanisms of these receptors, and can intervene in protein function and nucleate drug discovery efforts. Accordingly, I aim to identify and characterize small molecules that target allosteric sites in these signaling receptors, which are expressed on cell surfaces and bind ligands in the extracellular matrix, making them particularly accessible to exogenous modulation in-vivo.

  Complicit Organisations

1 Israeli organisation participates in PLATELET RECEPTORS.