Dihydrofolate reductase interactome: an unrecognised network that can control DNA synthesis and cell replication

We aim to characterise and map the interactome of dihydrofolate reductase (DHFR), a well-validated anticancer drug target. DHFR is an enzyme that catalyses a key reaction in the biosynthesis of DNA building blocks. Although therapeutics targeting DHFR are available for cancer treatment, there is frequent resistance against them. To address this issue, it is essential to fully characterise DHFR from its catalytic behaviours to regulatory network and this information help future drug development. DHFR binds to a wide variety of biomolecules other than its substrates, including its parental mRNA and enzymes responsible for post-translational modifications (PTMs). It is crucial to investigate these non-substrate interactions, as their functional roles have not identified.

We hypothesise that DHFR is embedded in a molecular network of interactions that control the activity of DHFR. We will characterise the effect of PTMs on DHFR catalysis, isolate the effect of mRNA binding and map the interactome of DHFR.

This work will advance our knowledge of DHFR and help future development of cancer therapies.