Research Projects

DNA methylation at CpG islands, particularly the methylation of cytosine, is a well-established epigenetic marker critical for cellular differentiation and development, with strong associations to various cancers. In 2009, it was discovered that the enzyme TET (ten-eleven translocation) can oxidize 5-methylcytosine (mC) into a series of modifications: 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxylcytosine (caC). While these modifications facilitate cytosine demethylation, the oxidized intermediates themselves serve as important developmental signals. Epigenetic modifications, particularly DNA methylation and hydroxymethylation, are pivotal in gene regulation and are implicated in diseases such as cancer and neurological disorders. Current methods for detecting these modifications often suffer from indirect detection, limited specificity, and extensive sample processing. This project aims to address these limitations by designing engineered proteins with high affinity and specificity for epigenetic DNA modifications. Furthermore, we will employ solution NMR spectroscopy to elucidate the structural properties of these engineered proteins and investigate their interactions with modified DNA. This NMR-based approach will enable the design and optimization of highly sensitive and specific protein probes, advancing the development of diagnostic and research tools in the field of epigenetics.