TNO is the coordinator of CarTarDis, will manage the entire project (WP5) and will be responsible for exploitation and dissemination (WP6). TNO will contribute its proprietary humanized mouse disease models and cell models and will be participant in WP2 (Target validation- in vitro and in vivo models) and in WP4 (Drug target prioritization).
Helmholtz Zentrum München
Helmholtz Zentrum München (HMGU) will lead WP1 (Target identification), and it will construct and update a database of existing and emerging CVD-related genetic markers, as well as provide human cohort molecular data including genotyping, epigenetic and metabolomic data. In addition, HMGU will contribute to statistical and bioinformatical analyses of omics-data and to the identification and confirmation of candidate drug targets.
Karolinska Institutet provides robust validation of candidate targets in a clinically relevant tissue by utilizing a large biobank of carotid atherosclerotic lesions in WP3 (Target validation – clinical tissue).
AstraZeneca’s role in the project will be 1) to organize and chair an expert group in WP4 (Drug target prioritisation) for this project composed of scientists from each work package with expertise in cardiovascular drug development, and 2) to guide the target validation and prioritization process aiming to deliver validated drug targets with realistic possibilities for further drug development in the area of CVD.
Hjartavernd will participate in WP1 (Target identification) by providing access to data from the human cohort studies that are being performed at IHA. In close collaboration with the other partners in WP1, the cohort data will be analysed for potential drug targets which will be further selected to a shortlist of candidate CVD targets. In addition, IHA will participate in WP4 (Drug target prioritisation).
Leiden University Medical Center
Leiden University Medical Center (LUMC) will chair and coordinate the human validation studies, and integrate the knowledge development within WP3 (Target validation – clinical tissue). LUMC will provide the clinical and pathological expertise required in WP3 (Target validation – clinical tissue). LUMC will coordinate the workflow required and validate candidate targets in relevant clinical material using tissue biobank validation workflow, and expand and extent the biobank activities in order to address unmet needs.
CardioGenx (CGX) role will be to develop in vitro models and animal models that can be used in WP2 (Target validation – in vitro and in vivo models) to study the biological role as well as validate the drugability of the candidate genes in several stages of cardiovascular disease, (including atherosclerosis and myocardial infarction).
Polygene’s role will be to develop animal models for the in vivo validation of targets as defined in WP2 (Target validation – in vitro and in vivo models). For this purpose, Polygene will use its proprietary technology to generate novel CVD disease models in connection with the existing ApoL3Leiden model, as well as provide rapid and reliable targeting services to cope with evolving demands of novel targets resulting from screening work in WP1 (Target identification), or in vivo validate targets resulting from WP3 (Target validation).
The role of Bioneer in CarTarDis will be to develop and implement RNA ISH-technologies as a contribution to the target validation work package (WP3). The work will comprise the optimization of in situ detection protocols for ncRNAs and mRNAs and the analysis of these in human vascular tissue samples from the Socrates and BiKE biobanks.
ImaBiotech will optimize sample preparation for clinical tissue in WP3 (Target validation – clinical tissue) and develop new methodology to evaluate potential small molecular weight biomarker. In fact, molecular profiling of metabolites will be performed directly on tissue sections with high specificity and sensitivity by utilizing matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). Correlation between specific distribution of molecules and tissue area will be achieved in order to highlight potential biomarker of the pathology. The identification and validation of candidate biomarkers found in tissue sections require establishing a global approach consisting in tissue selection, sample preparation, analysis parameters optimization, structural elucidation, statistical analysis and validation step.
Morphisto will develop immunohistochemical methods to profile and validate the chosen targets on clinical tissue samples in WP3 (Target validation – clinical tissue). On the basis of the expected results Morphisto will develop automatic analysis and screening methods particular for the defined targets in the specific project.
Umeå University will apply advanced in vivo and ex vivo imaging modalities to the various animal models developed in WP2 (Target validation – in vitro and in vivo models).
Molecular Profiling Consulting
Molecular Profiling Consulting (MPC) will translate the significant outcome from the available project data to relevant candidate drug targets. This involves direct interaction with WP1 (Target identification) and with WP4 (Drug target prioritisation). Additional bioinformatics support will be provided to the LCM-Tx/Px analyses in WP3 (Target validation – clinical tissue) where appropriate.