Use of metabolomic, lipidomic, and peptidomic approaches to the study of the composition of extracellular vesicles in the uremic context

• Grant number: 24/20880-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Jéssica Verônica da Silva
• Supervisor: Joachim Jankowski
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: Uniklinik RWTH Aachen, Germany
• Associated to the scholarship: 23/06583-0 - Vibrational nanospectroscopy applied to the study and characterization of extracellular vesicles in the uremic context, BP.DD

Abstract

The clinical diagnosis of a patient is based on the analysis of clinical tests, comparison with physiological and genetic standard parameters, high-precision medical imaging, and detection of metabolites in biofluids such as blood and urine. Despite the broadly available arsenal for measuring and characterising homeostasis, there are many reported cases of patients with similar symptoms and diagnostic parameters as well but undergoing diverse distinct pathologies. Moreover, it is not rare that different individuals present distinctive responses to the same treatment. The settling of precision and personalised medical diagnosis and therapy (theranostics), taking into account individual needs, and the potential response, is a great challenge for medicine in the future. Strategies to overcome this challenge include the determination of new biomarkers, the dynamic molecular response characterisation, and the design of new therapeutic methods. In this sense, cell-cell communication is essential for adequately operating multicellular organisms. This communication entails the transmission of signals between cells through direct interaction or the release of signaling molecules. Extracellular vesicles (EVs) have been recognised as significant facilitators of intercellular communication, playing a vital role in maintaining biological equilibrium. Besides, EVs are known to mirror the host cells where, after the uptake of these vesicles by the recipient cells, a cascade of signalling pathways begins, which, in turn, induces many pathophysiological changes in the recipient cells.However, few studies have demonstrated the role of EVs in several pathologies, including cardiorenal diseases. Moreover, it is well known that when kidney injury occurs, many compounds, the so-called uremic toxins, accumulate in the circulation, targeting other tissues. The accumulation of uremic toxins such as p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate leads to a loss of a substantial number of body functions. Therefore, the proposed project aims to characterise biomolecules (peptides, lipids, and metabolites) in EVs produced by renal cells in the uremic context observed induced by PCS and IS, using omics technologies by matrix-assisted laser desorption-time of flight mass spectrometry (MALDI-TOF-MS), identifying changes in metabolic pathways associated with uremia and cardiovascular impact. The results of the proposed project will help understand new mechanisms involved in cardiac and renal changes induced by the uremic compounds PCS and IS, mediated by EVs.