Research programme

Autoimmune diseases are immune-mediated disorders, highly heterogeneous entities for which the mechanisms of disease progression and therapeutic responses are only just beginning to be understood. Transcriptome models reflect distinct cell types involved in the development of the disease process. Our plan is to approach diseases by starting with an overview that allows us to drill down to the most relevant cell types in tissues and blood. Furthermore, by understanding the heterogeneity and similarities of diseases, we can also identify the best pathways to target with specific biological treatments. The diseases concerned are systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.

We will create a unique platform of translational groups across Europe and specialists in cellular and molecular profiling, imaging, sequencing and single-cell analysis. The aim will be to identify the molecular basis of the heterogeneity of each disease, and the mechanisms of non-response to treatment.

The platform will exploit already available existing clinical studies and clinical trials, but will be also producing new data from prospective multicentric studies. 

Committed students will be immersed in the latest advances of several new approaches and models of systems biology, and develop innovative concepts. In our approach, diseases can be viewed not as distinct clinical entities, but as new groups of shared molecular and cellular patterns that affect specific tissues through specialized cell types.
 

SIGNATURE stems from the H2020 IMI2-funded 3TR project, a transdisciplinary consortium to improve knowledge of the mechanisms related to treatment in seven different immune-mediated, allergic and inflammatory diseases. SIGNATURE will make use of the 3TR collected multi-dimensional molecular data from the recruited patients to go further in the research.

The Doctoral Candidates will undertake novel research to reach the following research objectives: 

Research objective 1

Comprehensive and single cell molecular characterization of affected tissues (WP1) using tissue biopsies of patients recruited of systemic lupus erythematosus and rheumatoid artritis obtained by the clinical groups working in European project 3TR, and single cell and imaging technologies. A suite of state-of-the-art single cell technologies will be applied providing data of increasing resolution.

Research objective 2

Identification of minimally-invasive biomarkers of tissue damage using body fluids (WP2). In order to establish biomarkers with minimal invasiveness and maximal clinical utility for the prediction of the response to therapy, flares and relapses, we will use biological fluids to perform single cell analysis, following a liquid biopsy strategy.

Research objective 3

Integrated analysis of the data using advanced bioinformatics/statistical pipelines and modelling methods (WP3) to identify trajectories, clusters, commonalities, and clinically relevant biomarkers and drug targets. We will develop inclusive models and algorithms for the integration of tissue, clinical and -omic data to be used as variables in the identification of classifiers and predictors of disease trajectories. The overall modelling of the immune system of every individual analyzed will complement the data.