Description

Research challenge:
Lipid membrane-packed extracellular vesicles (EVs) released by living cells are able to transfer their molecular cargo to recipient cells, which is accompanied by the reprogramming of the recipient cell functions. The release of EVs in the different body fluids in health and disease thus represents a biologically significant communication system, rendering them a promising tool for early detection and monitoring of diseases. The presence of EV-associated inflammation biomarkers and their link with underlying inflammatory processes in cardiovascular, neurological and immune diseases, cancer, and infection has been established. In conditions of serious illness the continuous and sensitive monitoring of inflammation biomarkers can be life-saving. 

A novel technology for continuous biomarker monitoring based on Particle Mobility Sensing (PMS) with single-molecule resolution is being developed by Eindhoven University of Technology and spin-off company Helia Biomonitoring. The technology allows for detection of mobility changes of micron-sized particles conjugated with specific affinity molecules for the targeted biomarkers [Visser et al., Nat Commun (2018) 9(1): 2541]. Assays for detection of inflammatory biomarkers are presently being developed on the PMS platform. In this IF project, the in-line sample fractionation system for EV isolation will be combined with PMS in order to study the feasibility of continuous EV-based inflammatory biomarker monitoring.

Approach:
The project will focus on developing a filter membrane-based column combining size selectivity with affinity for isolation of small EV subsets (50-150 nm), which can be directly coupled with the PMS platform. This fractionation system will initially be optimized using reference vesicles (synthetic liposomes and/or recombinant cell-derived EVs) spiked in buffer. Next, tests will be run with EVs secreted by a well-defined in vitro cell culture system showing reproducible inflammatory marker release kinetics after external stimulation (e.g. endothelial cell line stimulated with bacterial endotoxin to evoke an inflammatory response), and finally, with reference EVs spiked in plasma samples derived from different healthy donors to simulate real-life user conditions. System parameters (e.g. flow rate, column volume, membrane pore size, surface functionalization, etc) will be evaluated by assessing quantitative and qualitative aspects of the isolated EV fractions using state-of-the art methods (e.g. nanoparticle tracking analysis, western blot, transmission electron microscopy, small-particle flow cytometry). Inflammatory cytokine levels will be determined on intact versus lysed EV fractions using antibody arrays and/or ELISA as benchmarking technologies. Finally, proof-of-concept measurements will be performed with the PMS technology coupled to in-line fractionation of EVs to demonstrate the detection of 1 or 2 selected EV-associated inflammation markers in human plasma.

With this call, we invite researchers to submit their resumé (including track-record) and a one-page project description, that will be the basis for selecting candidates with whom we will collaborate for developing competitive MSCA-IF proposals.

 

Deadline application to VITO: Interested candidates should submit their resume (incl. track record) and a one-page note describing the project for which a Marie Curie grant will be applied, before Friday 17 April 2020 - 17h Brussels time.

 

Deadline MSCA-IF 2020: Wednesday 9 September 2020 17h Brussels time.

 

Qualification

We invite applicants to propose a more detailed and focused research approach within the scope of this MSCA-IF Fellowship as a part of their application. We are primarily looking for experienced researchers who wish to use this period as an opportunity to further develop their research, and to develop longer-term research collaborations with VITO and other institutions conducting research in the field.

 

 

The candidates as in principle must be eligible for a Marie Curie Individual Fellowship – please refer to the conditions set-out in the H2020 MSCA Work Programme.

 

The following assets will be advantageous:

- PhD in Biochemistry or Biophysics
- An excellent track record in research, necessary for being able to develop a competitive Marie Curie Fellowship application;
- Already published relevant research work in prestigious scientific journals;
- An open and cooperation-oriented nature, but with strong abilities for independent research work;
- Highly proficient in spoken and written English.

 


 

Offer

Initially, we offer assistance in developing competitive Marie Curie Individual Fellowship proposals.
 
Then, to successful applicants to the Marie Curie program, we offer;
- An exciting opportunity at VITO, the independent Flemish research organisation in the area of cleantech and sustainable development. Our goal? To accelerate the transition to a sustainable world;
- Participation in a dynamic professional research & innovation community;
- Flexible working conditions;
- An inclusive and friendly work environment;
- On-boarding assistance and other services.

 

 

Requisition

Location: 
Mol
Jobfield: 
Postdoc
ID: 
29180