Targeted proteomics and miRNomics to tackle biomarkers of infectious and neurodegenerative diseases and cancer

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Nowadays, research on molecular biomarkers is widely recognized as fundamental to improving the prevention, diagnosis, prognosis, monitoring and treatment of infectious and neurodegenerative diseases, and cancer. This project is focused on the development of innovative analytical methods for purification, preconcentration, separation, identification and characterization in biological fluids of proteins, glycoproteins and miRNA biomarkers, specifically related to COVID-19 (spike glycoprotein and nucleocapside protein), sepsis (procalcitonin protein), Parkinsons and Alzheimers diseases (alpha-synuclein protein and clusterin glycoprotein, respectively), chronic lymphocytic leukemia (miR21) and colorectal cancer (carcinoembryonic antigen glycoprotein, miR-421, miR130b-3p and miR27a-3p). Different strategies will be investigated, including the direct analysis of the biomarkers at the intact level or by bottom-up approaches, after their enzymatic digestion to obtain characteristic fragments (e.g. peptides, phosphopeptides, glycopeptides or glycans). Likewise, possible differences and alterations in the structure, composition or concentration of the potential biomarkers will be evaluated from a comparison of control and pathological samples. For these purposes, it will be primarily used high-resolution microscale separation techniques coupled to mass spectrometry (capillary liquid chromatography and capillary electrophoresis coupled to mass spectrometry, CapLC-MS and CE-MS) in full scan MS and tandem MS/MS modes, and online purification and preconcentration techniques, such as on-line solid-phase extraction capillary electrophoresis-mass spectrometry (on-line SPE-CE-MS). Finally, the application of advanced data analysis tools will provide a more systematic and comprehensive interpretation of the enormous amount of complex multidimensional data generated in the different comparative MS-based studies.