This project inves­ti­gates how sulfur-contain­ing amino acids regulate tRNA thiola­tion in endothe­lial cells, thereby control­ling protein trans­la­tion during vessel growth. Mapping the human endothe­lial tRNA thio-epitran­scrip­tome will uncover novel trans­la­tional control mecha­nisms and lay the founda­tion for poten­tial thera­peu­tic strate­gies target­ing patho­log­i­cal angiogenesis.

Trans­fer RNAs (tRNAs) play a central role in protein trans­la­tion, and mutations affect­ing tRNA-modify­ing enzymes are increas­ingly linked to human diseases. However, knowl­edge about human tRNA modifi­ca­tions remains fragmen­tary, with compre­hen­sive databases cover­ing only a fraction of known modifi­ca­tions. In prokary­otic systems, tRNA thiola­tion driven by sulfur mobiliza­tion controls trans­la­tion and stress responses. Whether a similar mecha­nism exists in human cells remains unexplored. This PhD project addresses the hypoth­e­sis that sulfur-contain­ing amino acids in the endothe­lial microen­vi­ron­ment regulate tRNA thiola­tion, thereby modulat­ing the trans­la­tional machin­ery during blood vessel devel­op­ment. We aim to map the endothe­lial tRNA thio-epitran­scrip­tome for the first time, identify sulfur mobiliza­tion pathways, and assess the impact of tRNA thiola­tion on trans­la­tion efficiency, codon bias, and tRNA fragmen­ta­tion. Functional studies will estab­lish links between dynamic tRNA thiola­tion and endothe­lial prolif­er­a­tion. If success­ful, this work will place the thio-epitran­scrip­tome at the center of novel thera­peu­tic strate­gies aimed at modulat­ing patho­log­i­cal angio­gen­e­sis in human diseases.