Biomolecular engineering to make epigenetic knowledge useful
We are working to develop new methods for detecting gene-specific DNA methylation that are amenable to clinical use.
Non-coding, epigenetic modifications to DNA, in addition to the underlying ATCG code, have been shown to regulate gene transcription and play an important role in diseases such as cancer. Recent studies indicate that one such modification in promoter regions, DNA methylation, has value as a predictive biomarker. Current clinical practice relies on chemical conversion via bisulfite treatment to distinguish between methylated and unmethylated DNA; such treatment can suffer from inaccurate results due to incomplete conversion and DNA degradation. Previously, we developed a biochip-based method that can be used to detect DNA methylation without requiring chemical conversion in order to make this information available to doctors accurately and at low cost. To improve sensitivity and reduce the number of cells required for analysis, we are engineering methyl CpG binding domain (MBD) proteins to epigenotype fixed cells from biopsied tissue. Through this work, we seek to enable widespread epigenotyping in order to improve cancer diagnostics and patient outcomes and to speed the process of biomarker discovery and validation.
A methyl binding domain in complex with DNA bearing a symmetrically methylated CpG site. Methylation of cytosines in this sequence context in gene promoters leads to reduced expression of certain proteins in many cancers.