Nanopore-Based Methotrexate Monitoring for RA and Cancer Patients
Pore-forming proteins embedded in artificial lipid bilayers have proven valuable in biotechnological applications, most notably for DNA sequencing. By applying a small (mV) voltage across the bilayer, an ionic current passes through the nanopore, enabling single-molecule detection and quantification of many biomedically relevant molecules.
The goal of this project is to measure methotrexate (MTX) levels in blood samples from patients treated for rheumatoid arthritis (RA), who frequently receive low doses of MTX, or cancer patients, who receive very high doses. To achieve this, the Cytolysin A (ClyA) nanopore in combination with the engineered dihydrofolate reductase (DHFR) protein will be used. When MTX is present, it binds to the engineered DHFR tightly, eliciting current blockades with longer residence times. These events can be counted and correlated to the MTX concentration in the sample. Additionally, computational modelling of protein movement, interactions, and data analysis (COMSOL, MATLAB, and/or Python, other tools as you prefer) will help deepen our understanding of the sensor’s functionality and optimise its performance. Ultimately, this approach aims to contribute to the development of point-of-care devices for monitoring MTX administration in both RA and cancer patients.
Contact information
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