MYOII-INFLAM · Non-muscle Myosin II orchestrates the inflammatory response by integrating adhesive and cytokine signaling and the mechanical properties of the inflammatory microenvironment
FP7 — People (Marie Curie Actions)
- Duration
- 2011-08-01 → 2015-07-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
Non-muscle Myosin II orchestrates the inflammatory response by integrating adhesive and cytokine signaling and the mechanical properties of the inflammatory microenvironment
This project has addressed how cells interpret mechanical and chemical cues of their surroundings (“the microenvironment”) and adapt their own mechanical properties to optimize cellular processes essential for human homeostasis. In the context of this project, the fellow has discovered several new molecular mechanisms the control the activation and function of a major mechanically active molecule, non-muscle myosin II, in response to inflammatory and non-inflammatory signals in the context of immune and non-immune cells. Such knowledge identifies new pathways of outstanding importance that could be exploited for the control of cellular mechanics in a variety of contexts, e.g. cancer cell migration, inflammation and stem cell-based cellular regeneration. This project, entirely conducted by the Fellow in an independent manner, has advanced the state of the art significantly in the field of cell biology, mechanobiology and cellular signaling. The Fellow has opened several additional lines of research that will not be described here, including mechanical development of tumor tolerance using cell-sized microchips, use of leukemia (Src) inhibitors to understand endothelial cell migration and use of microfluidic devices for 3D migration. In terms of management, this project has been a complete success, constituting the foundation of the Fellow’s independent career. The jumpstart provided by this grant is illustrated by a significant number of primary and review articles of which the fellow is the last and corresponding author. This is testimony of his scientific growth, based on research program that is 100% original and completely independent. Such program has garnered him the i+3 distinction, which is a quality indicator of research in the Spanish Research system. As part of his growth within the EU system, the Fellow has obtained an Associate/Tenured (indefinite) Professor position in the Universidad Autonoma de Madrid starting March 2016.
Data: CORDIS, © European Union
Project objective
This research aims to understand how inflammatory cues regulate the cellular responses of different cells implicated in inflammation. The main hypothesis is that non-muscle myosin II (NMII) is a central integrator of the different types of extracellular signals produced during the inflammatory response. The precise goal of the present proposal is to understand the regulation and function of the three NMII isoforms in the migration of cells implicated in inflammation, chiefly blood immune cells and cells that drive tissue repair and remodelling (fibroblasts) and vascularization (endothelial cells). This research will address the following objectives: 1) Identify specific kinases, phosphatases and regulatory sites that regulate NMII activation and assembly in a cell type-, stimulus-, isoform- and spatiotemporal-dependent manner. 2) Determine the signalling events and pathways through which the NMII isoforms control the response to inflammatory cues. 3) Elucidate whether the differences in expression and regulation of NMII underlie the different roles of these cells during inflammation. Successful completion of these objectives will provide novel insights on the basic cellular mechanisms of inflammation and bears potential to identify new therapeutic targets.
Original text from CORDIS.
Participants
- UNIVERSIDAD AUTONOMA DE MADRID · MadridCoordinatorSpain
Links
Data: CORDIS, © European Union