Our group is interested in understanding the activity, regulation, and inhibition of important epigenetic modifying enzymes, DNA methyltransferases.
Our DNA functions to store our genetic information; the sequence of our DNA provides the sequence for protein synthesis. However, more information than just protein sequence is needed - genes must be expressed at the right time and place. For example, all of your cells contain the same genetic information, i.e. DNA sequence. Yet, we are made up of a multitude of specialized cells. This diversity is accomplished by activating expression of some genes while inhibiting expression of others. Epigenetic mechanisms, heritable changes in genome function that do not alter the underlying DNA sequence, are one-way cells can modify gene expression. In humans, a common epigenetic mechanism of gene control is site-specific methylation of cytosine bases in DNA, which results in gene silencing. A family of proteins known as DNA methyltransferases (DNMTs) are responsible for establishing and maintaining methylation patterns in cells. Changes to the normal methylation pattern are associated with the development of many diseases, including neurological disorders and cancer. Understanding the activity, regulation and inhibition of these enzymes in vitro will aid in our understanding of their biological function in vivo as well as their role in disease.
Current projects in the lab include (1) investigating the biochemical consequence of disease-causing point mutations, (2) developing novel small molecule inhibitors that target DNMTs, and (3) probing the effect of local methylation levels on DNMT activity. Students in the lab get hands-on experience with common molecular biology and biochemical techniques including PCR, gel electrophoresis, column chromatography, and absorbance and fluorescence spectroscopy. Student projects often include site-directed mutagenesis and/or molecular cloning, protein expression and purification, DNA binding assays (e.g., electrophoretic mobility shift assays), and various kinetics assays to study DNA methylation activity.
Rebecca Fagan Switzer
Assistant Professor of Chemistry
209 Rooke Chemistry Bldg.