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Thesis
Home   /   Thesis   /   Multi-omics profiling to establish new molecular signatures predictive of respiratory infection

Multi-omics profiling to establish new molecular signatures predictive of respiratory infection

Genomics, proteomics Life Sciences Physiopathology

Abstract

Defect in the cystic fibrosis transmembrane conductance regulator (CFTR) is the causal agent of cystic fibrosis (CF). By improving the defective CFTR protein's function, the novel CFTR modulators represent a significant advance in CF management. However, these small molecules do not restore CFTR expression to normal levels and are a life-long treatment. In addition, not all patients predicted to be responders might experience the expected benefit. To understand the impact of the CF airway microbiology on the therapy efficacy, in collaboration with the CRCM of Montpellier and with the support of ‘Vaincre la Mucoviscidose’, we are carrying out multi-omics profiling of sputum samples collected longitudinally from patients starting the newest triple combination therapy Trikafta. This methodology allows for an in-depth analysis of human response, and the establishment of the microbial communities, both in terms of taxonomical structure and functional traits. To date, while new patients continue to be recruited, sputum collection has been completed for 81 patients (5-time points, 405 samples already collected). In this framework, the objective of this Ph.D. is to analyse and integrate the recorded multi-omics data and clinical parameters to identify correlations and promising sputum predictors of therapy efficacy and respiratory infection. The shortlisted candidates/pathways will be confirmed in a validation cohort via targeted approaches. In addition to contributing to a better understanding of the effects of the modulation of CFTR proteins on CF airway physiology, by boosting the discovery and validation of molecular signatures predictive of therapy efficacy and respiratory infections, this ambitious Ph.D. project will provide critical information for optimizing personal and precision medicine in CF treatment.

Laboratory

Institut des sciences du vivant Frédéric JOLIOT
Service de Pharmacologie et Immunoanalyse
Montpellier
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