European Proteomics Infrastructure Consortium – Providing Access
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The European Proteomics Infrastructure Consortium providing Access (EPIC-XS) started in January 2019. It brings together a consortium of world-leading, highly innovative European proteomics facilities with the shared goal of supporting excellent life sciences research in Europe. This is achieved by providing access to cutting-edge proteomics facilities, including receiving support in expert design and data analysis from on-site experts. The program also aims to develop and implement novel mass spectrometry (MS)-based proteomics and bioinformatics approaches to shape future life sciences research in Europe. It is funded as part of the European Union’s Horizon 2020 work program and is coordinated by Professor Albert Heck, project coordinator, and professor of biomolecular MS and proteomics at Utrecht University.
The Transnational Access in EPIC-XS consists of around 2400 access days to state-of-the-art proteomics facilities, evaluated by an international independent review panel, ensuring excellence and matching users with the best facility for their challenging research questions.
Miriam Abele and Franziska Hackbarth maintaining the liquid chromatography system of the mass spectrometer at the access site located at The Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Germany. Credit: EPIC-XS.
MS overview
Almost two-thirds of the way through this four-year project, scientific demand for access to cutting-edge proteomics techniques has resulted in over 250 applications. The geographical distribution of user applications stems from Central Europe in the main but also EU-associated countries such as Switzerland, Norway and Turkey, as well as representation from six of the EU 13 countries: Croatia, Poland, Slovakia, Slovenia, Cyprus and the Czech Republic. Remarkably, access has also been requested from Canada and America, indicating that EPIC-XS has achieved worldwide recognition.
Such significant requests for access are likely due to the many challenges currently faced by life science researchers. The widespread use of proteomics for many clinical laboratories and research institutions can be obstructed by the high cost of MS instrumentation including costs of maintaining these complex machines, their computing power, and expensive consumables. The need to acquire, train and retain highly qualified personnel means the long-term sustainability of MS equipment can be challenging.
Experiments conducted by users at the EPIC-XS access sites are already providing insights into:
- Protein-protein interaction studies
- Protein function
- Protein modifications
- Protein localization studies
Yielding information that spans the whole life science area including developments towards potential disease biomarkers that can ultimately be used for disease detection, treatment, and – in some cases –prevention, in developing food products that are safe and contribute to our good health and research for the development of novel designer crops. Here, we take a look at the work of some of the EPIC-XS Consortium's users.
Users from public and private research institutions
Dr Malgorzata Heidorn-Czarna, from the Department of Cellular Molecular Biology, University of Wroclaw, Poland, is investigating the consequences of rapid global warming on plant growth. Malgorzata’s work enlisted expertise from proteomic scientists at the Vlaams Institute Biotechnology - Gent University, Belgium. These scientists are experts in N-terminal COFRADIC procedures and are aptly suited in identifying protease substrates, helping Malgorzata understand the roles of OMA1 and i-AAA (FTSH4) mitochondrial membrane proteases in plant heat stress. The ongoing COFRADIC analyses will reveal specific cleavage sites of both proteases, a type of screen that cannot be carried out in Poland.
"By having transnational access to the expertise knowledge in the EPIC-XS consortium and the funding from the program, these experiments were made possible within a very short timeframe,” – Malgorzata.
Dr Esteban Gurzov, group leader at The Laboratory of Signal Transduction and Metabolism, Université libre, Brussels, has benefited from the advantages of transnational access at the Heck lab. Gurzov’s group focuses on studying the role of phosphatases in metabolism and the impact of obesity-related complications such as cancer. His vision is to study metabolic disorders in search of novel targets to treat these pathologies. The laboratory makes use of mouse models and human tissues with a variety of techniques to study cell dysfunction in metabolism, including animal models of metabolic disease, gene expression, RNAseq, siRNA, qPCR and Western blot analysis to identify relevant genes and signaling pathways.
“In the last months, my research has benefitted tremendously from the EPIC-XS initiative. It became possible to perform comprehensive screens for expressed and active posttransfusion purpura (PTPs) from extremely limited human liver tissue biopsies,” – Gurzov.
A patent for some of Gurzov’s research findings has already been filed.
Synergy: Access sites and researchers
The cooperation between users and the EPIC-XS access site research scientists has proven invaluable in answering current life science research questions and opened up several exciting possibilities for future research. The access site at the Bavarian Center for Biomolecular MS (BayBioMS), Technical University of Munich (TUM) has helped numerous researchers including Dr Sven Van Bael, KU Leuven, Belgium and Dr Sylvester Holt from the Université côte d’Azur, France. Van Bael's research focuses on the function of neuropeptides and their corresponding behavioral effects. Due to the broad evolutionary conservation of neuropeptide function, these are often studied in invertebrate model systems, in this case, the nematode Caenorhabditis elegans. A typical feature of neuropeptides is their in vivo processing, resulting in short (~10 amino acids) sequences containing relatively few basic amino acids making successful LC-MS/MS detection challenging. So far, most of Van Bael's peptidomics research was based on data-dependent acquisition (DDA) MS and while DDA is ideally suited for discovery purposes, its low overall reproducibility makes it unsuitable for accurate differential studies. The TUM access site was an easy choice due to their expertise with different targeted proteomic strategies such as parallel reaction monitoring (PRM) and data-independent acquisition (DIA).
“EPIC-XS has granted me the possibility to directly interact with experts in the field of targeted MS. Their experience and input were extremely helpful for my current research, and it will be something that I will take with me in my future career,” – Van Bael.
Dr Holt investigates the molecular effects of the perturbations derived from human cancer mutations within the yeast model system. In 2018 the group co-published the 1011 yeast genome resource in Nature, entailing yeast strains isolated from a wide range of natural and domestic niches. This established yeast resource will be used to investigate the mechanisms of drug resistance, specifically for mTOR inhibitors, and to compare those mechanisms between different yeast isolates.
“Without EPIC-XS this project would never have reached the current level of scientific excellence. Getting the EPIC-XS grant has been an extremely positive experience for me and the forward momentum for my scientific career,” – Holt.
EPIC-XS does not limit its access to specific genres in the life sciences, and has helped for much broader and complete research projects. This includes significant advancements in animal and veterinary science research, a field which, up until the last decade did not make conventional use of proteomics technologies. Dr André M. de Almeida, University of Lisbon, Portugal, fully supports this initiative.
“EPIC-XS is particularly important for areas such as animal and veterinary sciences where the use of proteomics is rather uncommon, although increasing in the last ten years. This allows for much broader and complete research projects, effectively complementing traditional approaches," – de Almeida.
Industrial users While the majority of users have come from academia and other research institutions, industrial users have also benefited from transnational access and direct communication with proteomics. Dr Kristina Masson, co-founder and global head of operations of Acrivon Therapeutics explains:
“Our project involves proteomic profiling of drugs in different tumor models. As a small biotech startup with very limited resources, the support from such a platform is incredibly valuable, and being part of this consortium has been a very good experience,” – Masson.
In contrast to the majority of EPIC-XS users, CEO and founder of Spectroswiss Dr Yury Tsybin’s main interest is in top-down and middle-down proteoform analysis. This research requires specific expertise and MS capabilities. His choice in selecting the MS for Biology Laboratory at the Institut Pasteur, France headed by Dr Julia Chamot-Rooke was an obvious one.
“The provided financial support is instrumental in realizing such projects. We envision the obtained results to have a direct impact on the way we (and others) will perform structural analysis of monoclonal antibodies, and potentially other complex proteins, in the near future,” –Yury.
Future impact
EPIC-XS can take credit for its achievements through its flexibility in providing access to all European scientists from novices to highly experienced researchers across all scientific divides within the life sciences.
The uniqueness of this framework has been strongly advocated by consortium members and users alike, for example in its provision of top-down proteomics. While attending the 17th annual US HUPO workshop on Top-down proteomics (8-12 March 2021), Yury Tsybin and Julia Chamot-Rooke’s (Institut Pasteur, access site manager) enthusiasm for EPIC-XS has compelled US researchers to consider implementing the EPIC-XS model in a similar US framework.
Currently, over 70 peer-reviewed publications are available with many more in preparation. The majority of these are from the four joint research activities (JRA’s) within the research groups of the consortium. This is not surprising, as EPIC-XS is only two years into its existence, and it can take users many months to compile data and prepare manuscripts.
A full list of user publications as well as details on proposal submission are available on the EPIC-XS website.
About the author
Martina O'Flaherty is the dedicated EPIC-XS project manager since the start of this proteomics initiative in January 2019. Martina has a background in biochemistry and MS and is based at Utrecht University where she also manages the Utrecht Molecular Immunology Hub project for the research of Albert Heck.
