Projets de recherche

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Doping occurs in a complex and dynamic environment. Often, the sporting system in which doping occurs comprises multiple hierarchical levels that is challenging to fully elucidate. To date, research in doping has typically focused on athletes and athlete support personnel at the sharp end of this hierarchy rather than the broader systemic factors that contribute to doping. To understand and optimise the behaviour of complex systems (i.e., the anti-doping system), the application of contemporary systems thinking-based methods has been recommended. Such methods allow for analytical modelling to be conducted to understand and identify the numerous interacting factors that influence system behaviour. This enables the identification of opportunities to intervene and optimise the overall system rather than its component parts.

Code: 21B07CR

All detection methods for ERA-doping are currently based on electrophoretic separation and Western blotting and due to its high sensitivity apply the same primary antibody (clone AE7A5 anti-EPO

antibody). Upon initiative of the grant applicant, a biotinylated version of the antibody was generated in 2018, which led to further increase in sensitivity and simplification of the method. The antibody

also became part of WADA TD2021EPO. One drawback of clone AE7A5 antibody is that it non-specifically binds to some proteins, which are present in human urine and blood. The non-specific

binding is caused by the fact, that the peptide used for generating the antibody contained two errors in the amino acid sequence. Hence, all doping control samples have to be first immunoaffinity-purified before electrophoresis. For this purpose, a different EPO antibody has to be used. To ensure better selectivity both the ISL [11] and the TD2021EPO, even if not totally mandatory, recommend that the CP differs from the ITP. Since no alternative to clone AE7A5 antibody is known so far, laboratories have to establish two different immunoaffinity purification procedures for ITP and CP. On the other hand, there are ca. 150 anti-human EPO antibodies commercially available, which have largely not been compared with clone AE7A5 antibody regarding sensitivity and selectivity. If an alternative antibody could be found, this would not only simplify EPO testing but would also generate more flexibility for the ITP and CP. Aim of the proposed project is a large scale evaluation of commercial anti-human EPO antibodies. About 100 antibodies will be tested regarding their sensitivity and selectivity in comparison with clone AE7A5 EPO antibody.

Code: 21T07NN

Detection of blood doping remain a challenge, and novel detection methods are warranted. In the present project, the aim is to evaluate the potential of changes in red blood cell proteins for detection of recombinant human erythropoietin (rhEpo) misuse at sea level and at altitude in males and females. The red cell protein content is expected to change with rhEpo treatment, as the transcription of genes coding for red cell proteins change during blood doping practices. Indeed, changes in a few proteins of red blood cells are known to change with rhEpo misuse. However, whether the changes in these proteins are sensitive and specific to rhEpo misuse and whether more sensitive and more specific proteins exist remains unknown. Additionally, it remains unknown whether hypoxic exposure or gender are confounding factors to these changes. To answer these questions, the present project will investigate more than 1000 different red blood cell proteins using mass spectrometry and identify the most sensitive and specific ones. Further, the present project will develop and validate a model for rhEpo detection based on the detected proteins. Our goal is to develop a ready-to-use robust method that will allow precise quantification of our novel biomarkers within approximately 4 h, from receiving the sample to the result.