Projets de recherche

Code: 253E03ER

Gene doping is a growing concern in athletic sports for both fair play and potential adverse health implications. One likely method of gene doping involves gene transfer: the introduction of additional copies of performance-related genes into cells by injection of a carrier virus. The method of packing of these genes into the virus creates unique sites that are not present in the human genome. These unique sites form the basis of the gene doping detection assays. By harnessing the parallel power of targeted next-generation sequencing (NGS), we can combine a suite of detection assays into one high-throughput screening test, greatly reducing costs compared to single target methods.

This project will construct a pool of 10 gene doping candidate target assays and test them on human plasma samples using a pipeline that has already been accredited to ISO 17025 for equine samples. For confirmatory analysis, single-target qPCR assays will be employed in accordance with current WADA guidelines on technology use. In addition, qPCR products are sequenced to verify using our novel method.

As a ‘proof of principle’ screen, human plasma samples available from commercial suppliers will be processed and assessed alongside spiked samples. For each gene, a confirmatory qPCR assay will be designed and tested, culminating in mock confirmatory tests as a proof of principle for future regulated validation.

The aim of this project is to increase knowledge on psychosocial factors that lead to the intention to dope. A quasi-experimental study based on the use of questionnaires and validated scales will be used.

The purpose of this research is to conduct a pilot investigation of how Brazilian coaches perceive anti-doping (values, challenges, priorities and cultural perceptions).

The research involves the use of an integrated framework of complexity theory and methods-systems thinking, intervention design, computational modelling and simulation across three research phases. The project will focus on understanding the broader systemic influences on doping and will identify the causal influences on doping behaviors and systemic structures enabling doping.

Subsequently, the project will design a set of novel interventions to be simulated in a computational model for their effectiveness. The outcomes will include new tested interventions ready for implementation in the real world.

This project aims to address the unique need of standardizing frameworks to guide evaluation, monitoring, and assessment of education programs/interventions. By collating existing knowledge on the psycho-socialbehavioral drivers of doping behavior and developing a cocreated framework for their integration into the assessment of the evaluation and monitoring of anti-doping education.

The project will also pilot this new framework in collaboration with CHINADA and its regional anti-doping branches in China.

The aim of the proposal is to collaborate with athletes who have intellectual impairment (II) to co-create anti-doping educational resources that better serve their needs. The project will be conducted through 3 phases.

In Phase 1, they will establish National (NWG) and International (IWG) working groups of athletes with II to cocreate a survey that is disseminated to athletes and asks them what the most pressing educational topics require adaptation and how they prefer to be taught.

In Phase 2, they will disseminate the survey to athletes with II to establish the anti-doping educational topics requiring adaptation and how these should be taught.

In Phase 3, they will co-create anti-doping educational resources on the topics identified in Phase 2 with NWG and IWG and disseminate these to international and national organizations.

Code: 25T242B04CM

Autologous blood transfusion (ABT) using cryo-preserved red blood cells (Cryo-RBC) is a method that will enhance athletic performance in endurance events. Cryo-RBC can be stored longer than regular cold-stored RBC, making them a better option for athletes who might use blood transfusions as a form of doping. Our research aims to create a reliable test to identify Cryo-RBC in blood using specific markers.

In our earlier studies we used various techniques to analyze blood samples after doping humans by ABT. While we developed strong models to predict ABT, they didn't always work well with real-world samples. This is due to individual differences in blood responses, random breakdown of proteins, and the small amount of Cryo-RBC present in the blood after transfusion.

Before conducting more studies, we must improve how we sort and concentrate Cryo-RBC. We plan to use several methods to detect the specific markers for Cryo-RBC better:

Fluid Properties: Changes in the physical properties of Cryo-RBC can be seen after freezing, which may help us identify them.

AI Sorting: Advanced AI technology can analyze and sort Cryo-RBC based on their shape and structure.

Biological Filters: Tiny particles released from red blood cells can help us focus on damaged proteins and peptides from Cryo-RBC.

By combining these methods, we aim to improve our ability to detect blood doping using Cryo-RBC. We have several goals, including understanding the fluid properties of Cryo-RBC, sorting them using AI, and concentrating specific biomarkers to help in identifying ABT. Overall, this research could lead to better methods for detecting blood doping in sports.

Code: 252C04GH

6β-chlorotestosterone (6β-Cl-T) is a new steroid-like compound reported in the blank market in recent years. Metabolic profile of 6β-Cl-T in human urine after an oral dose of 40 mg was studied in our previous report. Ten new metabolites including four Phase I metabolites and six Phase II metabolites were characterized and potentially identified. Furthermore, the influence on steroidal profile after administration of 6β-Cl-T was evaluated by GC-MS/MS. Results showed that 6β-Cl-T could transform to T in one male volunteer, so as to cause an AAF for T and its metabolites. In order to figure out the origin of T in this male volunteer, GC-C-IRMS was applied in the two samples at abnormal high T/E ratio values of 6.86 and 5.0 (> 4). In total, δ13C values were determined in 5 target compounds (TCs), which were T, 5αAdiol, 5βAdiol, A, and Etio. However there was no significant change in increasing testosterone levels for women individuals and UGT2B17 gene deletion (del/del) male individuals, which might cause false negative results in these people.

The current application is a follow-up study of our previous project, and the objectives of this research are to (1) find the dechlorinated metabolites (biomarkers) and conversion mechanism from 6β-Cl-T to T, aiming to mitigate the drawback of conventional ABP strategies failing to be effective for UGT2B17 gene deletion (del/del) population after medication of 6β-Cl-T, (2) employ biological methodologies for the synthesis, purification, and enrichment of the principal metabolite(s) of 6β-Cl-T, and (3) chemical synthesis of metabolites, and finally distribute metabolite(s) to WADA-accredited doping control laboratories.

Code: 252C03BL

In steroid hormone testing, the biological passport indicators of athletes, which serve as longitudinal monitoring parameters, are susceptible to interference from various factors, and 5α-reductase inhibitors represent one such co-founding factor. Given that other 5α-reductase inhibitors, such as finasteride and dutasteride, are already monitored for their potential impact on steroid detection in anti-doping, comprehensive metabolic studies of epristeride are crucial to understand its impact for doping control purposes. Epristeride, a novel non-competitive inhibitor of type II 5α-reductase, has emerged as a potential therapeutic alternative for benign prostatic hyperplasia. This study aims to investigate the metabolic characteristics of Epristeride and elucidate its metabolic pathways in humans, investigating its impact on the steroid indicators of athletes' biological passports, examining the differences in effects among populations with different genotypes, and comparing the variations in effects between the Chinese population and the Caucasian population. Thereby providing a scientific basis for assessing its potential risks to athletes and doping control.

Code: 252A09MT

Many substances (also some of those belonging to the WADA Prohibited List) tend to enrich (or deplete) in red blood cells and, thus, will show significantly deviating concentrations in whole blood (such as DBS) and plasma (or serum) samples. For an accurate evaluation and interpretation of analytical results obtained from DBS analyses, the information about the RBC-to-plasma-ratio for each substance is crucial, not only in the context of quantitative result management. The RBC-to-plasma-ratio can be characterized by a simple and straight forward in-vitro approach with incubating the substances of interest in whole blood, followed by the separate analysis of the cells and the plasma fractions. With those experiments, the partitioning of nearly all prohibited substances between erythrocytes and blood plasma can be determined. These data will be of substantial importance for future result management processes where concentrations of MRL- and threshold-substances in DBS are to be evaluated.