| Project Detail |
The role of skin microorganisms in drug metabolism
Our skin is home to millions of microorganisms that ensure tissue homeostasis and function. Emerging evidence also suggests a role of the skin microbiome in drug metabolism as it contains a large reservoir of metabolic enzymes. Following chemotherapy, many patients develop hand-foot syndrome (HFS) associated with redness and swelling in the palms of the hands and soles of the feet. The EU-funded DiAMonD project seeks to delineate the role of the skin microbiome in protecting against a skin adverse drug reaction. Researchers will isolate and study microbes present in HFS alongside their capacity to metabolise specific chemotherapeutic drugs. Results will pave the way for personalised interventions following chemotherapy to avoid HFS.
The microbiome plays relevant functions on human health and disease, including roles in the efficacy and security of drug treatments. Capecitabine is a pro-drug of 5-fluorouracil, which is an active metabolite that targets tumor cells. This treatment is used for diverse cancers, including colon tumors, and is commonly associated with diverse adverse reactions such as the hand-foot syndrome (HFS), a skin deterioration for which there has not been discovered its causal mechanism. Preliminary data suggest that some skin microbes interact with 5-flourouracil.
Here, I aim to study the dynamics and features of the skin microbiome of patients treated with capecitabine. Using massive parallel sequencing methods, I will look for microbial taxa, genes and/or functions associated with the presence/absence of HFS adverse reaction. Based on those data, I will select appropriate conditions to isolate microbial taxa likely implicated in HFS and I will study their ability to metabolize capecitabine and 5-florouracil. Then, with those microbes showing this activity, I will analyze their genomes and transcriptomes in presence/absence of these drugs to select candidate genes involved in this drug metabolism. Afterwards, I will perform docking methods to decipher more precisely the likelihood of the encoded protein to interact with the drug. Finally, I will validate this data with the phenotypic study of knock-out mutants lacking selected genes likely implicated in the drug metabolism.
This project will provide understanding related with the roles of the skin microbiome in the appearance or protection against a skin adverse drug reaction. This knowledge may be used for the advance of a precise and personalized medicine in which the individual microbiome can be considered. The proposed project will allow me to gain skills in novel methods of microbiome studies and in project management, and will extend my research network boosting my career towards a mature and independent stage. |
