WG leader: Fransisco Sanchez-Madrid

Co-WG leader: Pia Siljander

Aims:

As is the situation described for WG1, very good research has been done throughout pockets on Europe indication microvesicles and/or exosomes have a role to play in normal, healthy conditions, including communication necessary for immune-protection, embryonic- and other stem celldifferentiation, platelet function, embryonic cell-derived, etc. So, in the context of above, data from COST Action members’ prior research considered suitable for integrating and/or directly comparing will be co-analysed in order to establish the breadth of our collective understanding of the physiological role(s) of ME. This will form a solid foundation to advance upon in follow-on collaborative efforts exploring the role of these vesicles under normal, healthy circumstances.

ME, for example, have emerged as potent vehicles for cell-cell communication since the discovery that they contain functional RNA, protein (and possibly DNA) molecules that can functionally interact with target (acceptor) cells. The content of ME, it seems, is not always simply a straightforward reflection of the content of the cell of origin. Specific populations of RNAs are selectively packaged into exosomes, indicating the existence of an as-yet unknown mechanism that controls the sorting of specific RNAs into exosomes. The information contained in ME can influence or even direct the fate of the target cell, for example triggering its activation, migration, differentiation, or promoting apoptosis, with the functional consequences of this transfer of genetic information depending on the origin and status of both the donor and recipient cells. The transfer of material via ME to target cells can occur both in a cell-cell contact dependent manner e.g. via specialised junctional structures such as synapses or at longer distances.

These findings have revealed important, novel cell-cell communication modes and point to new ways to modulate cell-cell interactions and their responses. It is timely that this information be brought together in an organised and open manner, evaluated and progressed upon through collaborative European research efforts.

Tasks:

Integrating and critically evaluating available data on physiological roles of ME

• Collecting current knowledge in ME biology and summarising the state-of-art biological significance of ME in health and identifying substantial gaps in our understanding of ME under normal, healthy, circumstance;
• Subsequently making this information available, through ME-HAD, to all interested parties.

Extending existing research to further determine the role of these vesicles under normal, healthy circumstances

• Ensuring that subsequent analysis of the physiological relevance of ME, during the course of ME-HAD’s 4 years and beyond, are properly designed and performed (e.g. optimal technologies, learning from WG1, adequately powered, etc.) to result in meaningful outputs;
  Exploring the mechanisms regulating ME-mediated transfer of genetic information and proteins from cell-to-cell;
  Exploring the plasticity of ME release in relation to the (activation) status of the producing cell, target cell and microenvironment;
  Defining important future research topics and publication of a joint White paper.