Periodic Reporting for period 1 - MIRACLE (Multilevel inflammatory regulation in cardiometabolic disease)
Periodo di rendicontazione: 2024-02-01 al 2026-01-31
The MIRACLE programme brings together leading academic and biotech industrial partners to train the next generation of innovation-minded researchers who can advance precision medicine approaches for cardiometabolic diseases (CMD).
CMD are among the most common and burdensome health conditions worldwide. This group of conditions includes cardiovascular and metabolic disorders such as atherosclerosis, type 2 diabetes, and non‑alcoholic steatohepatitis. These highly prevalent diseases are closely associated with metabolic imbalances, including obesity and insulin resistance, and are characterised by chronic, low-grade inflammation that gradually damages tissues and contributes to disease progression. Despite their high prevalence and impact on healthcare systems, the biological mechanisms driving inflammation in CMD remain incompletely understood.
Current anti-inflammatory therapies used to manage cardiometabolic conditions often act broadly on the immune system. However, these therapies frequently lack specificity and do not fully address the diverse mechanisms underlying CMD. This highlights the need for more precise therapeutic strategies that target the specific pathways responsible for disease-related inflammation.
The MIRACLE programme aims to expand current knowledge of the mechanisms that regulate inflammation in CMD and to support the development of more targeted therapeutic strategies. The project combines expertise from academic research and biotechnology sectors and integrates cutting-edge technologies to investigate how local tissue environments, cellular interactions and molecular signals contribute to chronic inflammation in CMD.
To achieve these goals, the programme follows a multidisciplinary research strategy. First, advanced single-cell technologies are applied to characterise diseased tissues at multiple biological levels. Second, the project examines how local environmental signals shape cellular communities and influence interactions between immune and non-immune cells. Third, multiple layers of biological data are integrated to identify regulatory networks that control inflammatory processes. Finally, the knowledge generated is used to support the evaluation of potential therapeutic strategies in advanced experimental models.
Beyond its scientific objectives, MIRACLE is designed as a comprehensive doctoral training programme that integrates academic and non-academic sectors. It equips Doctoral Candidates with advanced interdisciplinary expertise spanning molecular biology, computational analysis, translational research, and innovation management. This integrated approach strengthens Europe’s capacity to generate highly skilled researchers capable of bridging fundamental discovery and therapeutic development.
CMD are among the most common and burdensome health conditions worldwide. This group of conditions includes cardiovascular and metabolic disorders such as atherosclerosis, type 2 diabetes, and non‑alcoholic steatohepatitis. These highly prevalent diseases are closely associated with metabolic imbalances, including obesity and insulin resistance, and are characterised by chronic, low-grade inflammation that gradually damages tissues and contributes to disease progression. Despite their high prevalence and impact on healthcare systems, the biological mechanisms driving inflammation in CMD remain incompletely understood.
Current anti-inflammatory therapies used to manage cardiometabolic conditions often act broadly on the immune system. However, these therapies frequently lack specificity and do not fully address the diverse mechanisms underlying CMD. This highlights the need for more precise therapeutic strategies that target the specific pathways responsible for disease-related inflammation.
The MIRACLE programme aims to expand current knowledge of the mechanisms that regulate inflammation in CMD and to support the development of more targeted therapeutic strategies. The project combines expertise from academic research and biotechnology sectors and integrates cutting-edge technologies to investigate how local tissue environments, cellular interactions and molecular signals contribute to chronic inflammation in CMD.
To achieve these goals, the programme follows a multidisciplinary research strategy. First, advanced single-cell technologies are applied to characterise diseased tissues at multiple biological levels. Second, the project examines how local environmental signals shape cellular communities and influence interactions between immune and non-immune cells. Third, multiple layers of biological data are integrated to identify regulatory networks that control inflammatory processes. Finally, the knowledge generated is used to support the evaluation of potential therapeutic strategies in advanced experimental models.
Beyond its scientific objectives, MIRACLE is designed as a comprehensive doctoral training programme that integrates academic and non-academic sectors. It equips Doctoral Candidates with advanced interdisciplinary expertise spanning molecular biology, computational analysis, translational research, and innovation management. This integrated approach strengthens Europe’s capacity to generate highly skilled researchers capable of bridging fundamental discovery and therapeutic development.
During the first reporting period, the MIRACLE programme successfully initiated and advanced its core scientific activities across all research work packages, establishing the experimental, analytical and collaborative foundations required to achieve the project objectives.
Within WP1, the programme focused on identifying immune cell populations that contribute to chronic inflammation in CMD. Using advanced single-cell RNA sequencing technologies, researchers analysed immune cells from relevant biological samples to characterise cellular diversity and identify transcriptional programmes associated with disease. Additional experimental work investigated molecular pathways regulating macrophage activation and metabolism, and experimental models of liver disease were established to study cellular plasticity.
Within WP2, the programme investigated how immune cells interact with their surrounding tissue environment during cardiometabolic disease. By combining spatial and single-cell analytical approaches, the research aims to better understand how local environmental cues influence immune cell behaviour and how cell–cell interactions contribute to persistent inflammation within diseased tissues. Initial datasets and analytical pipelines have been established to enable the mapping of immune cell populations and their functional states within tissue microenvironments.
Within WP3, the programme integrated multiple layers of molecular information to understand how genetic variation, epigenetic regulation and metabolic states influence immune cell behaviour in CMD. This work combines different omics approaches to identify regulatory networks that shape inflammatory phenotypes and to explore how genetic and environmental factors interact to influence disease-related immune responses.
Within WP4, experimental and computational disease models are being established to evaluate targets identified in earlier work packages and to provide platforms for future testing of potential therapeutic interventions.
Within WP1, the programme focused on identifying immune cell populations that contribute to chronic inflammation in CMD. Using advanced single-cell RNA sequencing technologies, researchers analysed immune cells from relevant biological samples to characterise cellular diversity and identify transcriptional programmes associated with disease. Additional experimental work investigated molecular pathways regulating macrophage activation and metabolism, and experimental models of liver disease were established to study cellular plasticity.
Within WP2, the programme investigated how immune cells interact with their surrounding tissue environment during cardiometabolic disease. By combining spatial and single-cell analytical approaches, the research aims to better understand how local environmental cues influence immune cell behaviour and how cell–cell interactions contribute to persistent inflammation within diseased tissues. Initial datasets and analytical pipelines have been established to enable the mapping of immune cell populations and their functional states within tissue microenvironments.
Within WP3, the programme integrated multiple layers of molecular information to understand how genetic variation, epigenetic regulation and metabolic states influence immune cell behaviour in CMD. This work combines different omics approaches to identify regulatory networks that shape inflammatory phenotypes and to explore how genetic and environmental factors interact to influence disease-related immune responses.
Within WP4, experimental and computational disease models are being established to evaluate targets identified in earlier work packages and to provide platforms for future testing of potential therapeutic interventions.
There are no relevant published results generated yet at this stage of the project.