INFORMAZIONI SU
MOHAMMED REFAI Fathima Shaffra
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Supervisori: Prof. Esposito and prof. Piano Dr. Hala Systems Biology using C. elegans: The influence of genetic variations on drug response |
| Inter-individual genetic variation can have profound effects on drug action, influencing drug efficacy and safety, yet the underlying mechanisms are poorly understood. Studying how natural genetic variations affect individual responses to drugs is a major challenge in pharmacogenomics. The nematode Caenorhabditis elegans is a powerful model genetic system to study animal development and physiology, leading to five Nobel Prize winners. Paralleling human data, diverse natural strains of C. elegans can react differently to the same drug. The C. elegans Natural Diversity Resource (CeNDR), harbors genomic information about hundreds of C. elegans strains that were collected worldwide from natural habitats. A high-throughput robotic platform with quantitative image analysis for C. elegans drug screening is available for the proposed project that aims to investigate the effect of chemical perturbations in a variety of natural C. elegans strains and disease mutants. The project will follow three specific aims. First, known compounds showing nematicidal or paralytic activity will be studied for their quantitative responses (IC50) in the genetically diverse natural isolates. Second, genome-wide association (GWA) mappings coupled with metabolomics studies will be used to determine the molecular cause of phenotypic variation. Third, the specific case of an established amyloid aggregation model using C. elegans will be explored in the context of transgenic mutants, diverse genetic backgrounds, and different drugs. The findings will potentially enhance our understanding of personalized medicine and contribute to the development of more effective and tailored therapeutic interventions. | |