As a recipient of a doctorate in biomedical sciences, I am obliged to enthusiastically educate people about science. Too often I hear people characterize science as boring: I want to challenge that misconception. This is important because for many people interactions with me may be their only experiences with a scientist. To emphasize this strategy in my lessons, I will use inquiry-based learning activities where students critically engage with primary sources of data, and case studies related to current and historical events to highlight how interwoven science is in our society. These activities will be structured to encourage team-based learning.
The overarching theme of my independent research will be to study the role of histone ubiquitylation in epigenetics, with a focus on the link between histone ubiquitylation and DNA methylation (DNAme). The role of ubiquitin conjugation in regulating protein function, degradation, and localization has long been established; however, histone ubiquitylation is emerging as a critical epigenetic mark. While the functional consequences of ubiquitylation to a few specific lysines on histones are known, the regulatory role of ubiquitin in epigenetics is underappreciated, highlighted by the number of sites of histone ubiquitylation with unknown functions identified with mass spectrometry.
Recent studies performed by myself (Harrison et al. eLife 2016) and others have identified a link between histone ubiquitylation and DNAme. DNAme is a heritable epigenetic modification occurring on CpG dinucleotides and has been extensively studied as a repressor of gene expression. Changes in DNAme patterns are required for development and differentiation and are one of the hallmarks of cancer. Indeed, carcinogenesis is accompanied by a reduction in bulk DNAme and aberrant de novo methylation. However detailed knowledge about how DNAme patterns are established and degenerate in disease is lacking. Therefore, mechanistic understanding of how histone ubiquitylation regulates DNAme will provide insight into development and disease and may provide avenues for novel therapeutics.