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Project 1: Cross-platform comparison for plasma/serum/urine EV immune-isolation & characterisation

This project will include the development of exosomes immune affinity (IA) isolation methods and comparative validation of multiple solutions as self-standing purification tools, as well as integral parts of assays for exosomes (protein and RNA) quantification and characterisation.

Location: HansaBioMed, Estonia

Supervisor: Dr Antonio Chiesi


Project 3: Affinity Filters capable to specifically capture EVs

In this project, for separation of EV sub-populations from human plasma, filters will be developed by
advancing upon GVS’s existing filters e.g. SPEEDFLOW™ POSITIVE and LEUKOSAFE™. These are capable of filtering plasma without varying properties while simultaneously capturing viruses (comparable size to EVs; at 20-400 nm).

Location: GVS S.P.A., Italy

Supervisor: Dr Ing Soccorso Gaeta


Project 4: Development of a biological reference material

The aim of this project is to develop a biological reference material that behaves the same as, but can
be easily distinguished from, body fluid-derived EVs. Taking advantage of a protein that regulates budding of viruses, this project will produce, isolate and characterize highly fluorescent viral-like particles (VLPs) from HEK cells.

Location: Ghent University, Belgium

Supervisor: Prof An Hendrix


Project 5: Advance from the current “gold-standard” methods for EV isolation, further develop methods for characterising EVs and investigate means to exploit EVs for clinical application

In this project, 1). In order to develop monoclonal antibodies (mAbs) that will differentially recognise and capture different EV sub-populations, mice will be injected with EVs isolated from cell line culture supernatants and/or biological fluids. 2). Mice will be immunised with different tissue or cell-specific antigens.

Location: Semmelweis University, Hungary

Supervisor: Prof Edit Buzás


Project 6: Further develop methods for characterising EVs utilising advanced technologies and assess patho-/physiological relevance of EVs and their potential to be exploited as biomarkers

This project will involve systematic characterisation of EVs generated during the course of different types of cell death (e.g. apoptosis or necroptosis). For this, different cell death types will be induced in vitro using established protocols.

Location: Semmelweis University, Hungary

Supervisor: Prof Edit Buzás


Project 7: Defined EV-subset analysis in blood by flow cytometry

The aim is to define protein-based platforms to identify and analyse EV subsets derived from different cell types e.g. immune cell or cancer cell-derived EVs, in blood (from female and male donors) and to exploit their biomarker potential.

Location: Utrecht University, Netherlands

Supervisor: Prof Marca Wauben


Project 8: Tetraspanins role in egulation of EV composition by tumour cells & metastases

This project will examine how tumour cells regulate the composition of their EVs at different stages of cancer progression; specifically, epithelial-mesenchymal transition (EMT) and the reverse program of mesenchymal-epithelial transition (MET) will be examined as central processes of metastases formation and progression.

Location: University Freiburg, Germany

Supervisor: Dr Irina Nazarenko


Project 9: Exosomal/EV-recruited splice variants & mutated oncogenes contributing to cancer progression

The appearance of activating mutations and alternative splicing events of oncogenes leads to tumour heterogeneity and counts as one of the hallmarks of cancer progression and metastatic spread, which are frequently accompanied by the acquisition of therapy resistance. Here, this project will assess how distinct splice variants and mutated forms of EGFR, c-KIT, KRAS and BRAF are recruited to the EVs, and how these events are linked to the application of a corresponding drug, e.g. cetuximab and imatinib.

Location: University Freiburg, Germany

Supervisor: Dr Irina Nazarenko


Project 10: Immune modulatory capacity of EV-subsets in blood of healthy and diseased subjects

Editing of immune responses by EVs is a shared mechanism in cancer and chronic inflammation. However the result of EV-mediated immune modulation, either activation or inhibition of the immune response, is not well predictable. The aim of this project is to identify and functionally analyse circulating immune modulatory EV subsets from healthy and diseased (chronic inflammation and cancer) subjects (human and experimental mouse models) and to unravel their role in patho/physiological processes.

Location: Utrecht University, Netherlands

Supervisor: Prof Marca Wauben


Project 11: Development of bioinformatics tools to explore and compare cellular and EV-contents

This project will analyse datasets, from both collaborating TRAIN-EV labs and those publically-available, to generate appropriate pipelines for the robust analysis of EV-related contents. In contrast to the relatively stable content of cells, EVs contain variable biological products and organelles that need to be quantified and compared. To improve the analysis of EV content, there is a need to identify “housekeeping” molecules or other standards that allow comparison and meta-analysis of datasets produced by different labs.

Location: Bioinf2Bio, Portugal

Supervisor: Prof Carla Oliveira


Project 12: EV membrane camouflaged nanoparticles as biomimetic drug delivery platform

Metastasis is responsible for >90% of cancer-associated mortality; thus the clinical need to prevent or target metastasis is high. EVs carry targeting motifs for cell-type specific recognition. Gold nanoparticles (AuNP) associated with a chemotherapeutic and camouflaged with EV membranes could be used as biomimetic drug delivery platforms with the potential for controlling metastatic disease. In this project, density gradient purified EV membranes will be fused onto AuNP (correctness of orientation and efficiency will be checked by EM, high resolution flow cytometry, and surface potential measurements).

Location: Ghent University, Belgium

Supervisor: Prof An Hendrix


Project 13: Investigating the relevance of EVs in breast cancer

This project will further advance on our in vitro and in vivo studies of EVs associated with triple-negative (TNBC)24 and HER2-overexpressing breast tumours25 -which are predominant female diseases (99%)- to identify their biomarker contents and assess their potential to prepare the pre-metastatic niche for metastasis.

Location: Trinity College Dublin, Ireland

Supervisor: Prof Lorraine O’Driscoll


Project 14: Investigating the relevance of EVs in prostate cancer

Advancing on our pre-clinical and translational clinical trials studies of EV related to prostate cancer27 (which affects males only), this project will further elucidate their relevance in communicating drug resistance from cell-to-cell and also their potential as bundles of diagnostic and predictive biomarkers.

Location: Trinity College Dublin, Ireland

Supervisor: Prof Lorraine O’Driscoll


Project 15: Immune functions of EV types secreted by tumour and immune cells

This project aims to identify both the specific and common effects, on immune cells, of the different types of EVs secreted by tumour cells and by immune cells. This will be done by in vitro co-culturing of various immune cells (e.g. myeloid cells – monocytes, macrophages, dendritic cells (DC)-, T lymphocytes – helper and regulatory CD4+,cytotoxic CD8+ and natural killer cells with sub-types of EVs (exosomes, ectosomes) isolated from either different tumour cell lines or non-tumoural cell lines and primary immune cells, representing both female and male donors.

Location: Institut Curie, France

Supervisor: Dr Clotilde Théry

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