Lily Miller, an IPiB graduate student, will be defending her Ph.D. research on August 17, 2023.
Miller’s work in the Denu Lab investigates how enzymes add methyl groups to modify histone proteins.
We often see representations of DNA as elongated strands of the famous double helix, but in our bodies DNA is tightly wound around proteins called histones. Histone modifications are among the many ways that cells can identify which genes should and should not be expressed. This type of modification – in which a change impacts gene expression without altering the genetic code itself – is known an epigenetic change.
“Your hand cells have the same DNA as your eyeball cells, but obviously they’re not the same kind of cell,” explains Miller. “The [histone] modifications are a way of helping our bodies read the DNA in a way that makes sense. It’s like a pair of special glasses. Without the glasses, you just see kind of a jumble of code. But with the glasses, you can read what it says. The DNA itself doesn’t change, but each cell is told the right way to read it. That’s essentially what epigenetics is.”
Histone methylation is so essential to cell function that, even in an environment in which methyl donors (a molecule known as SAM that donates a methyl group) are not readily available, enzymes will still ensure that methylation occurs. “There’s this kind of de novo methylation that happens in the absence of SAM,” says Miller. “Methylation is so important that the cell still uses energy so that enzymes can methylate histones.”
Miller studies a histone region in which methylation results in more tightly wound DNA, making some regions of the DNA less accessible to the transcription factors necessary for gene expression. This modification ultimately impacts which genes are expressed and which are silenced. Mutations to the enzymes responsible for methylation can result in inappropriate expression or suppression of genes, which can lead to diseases such as cancer.
Miller’s research, which has been published in the Journal of Biological Chemistry, focuses on the kinetics behind the catalytic mechanisms responsible for methylation, and the rates at which enzymes methylate DNA.
Having worked in an enzymology lab at Codexis before joining the IPiB program, Miller knew she was interested in graduate school as an opportunity to further explore how enzymes work. Kinetics, however, was a new field to her. “Nothing in biochemistry is black and white,” says Miller, “but kinetics is almost like the bridge between math and biology. It’s just a very logic-based way of exploring the parameters that describe an enzyme.”
While John Denu’s expertise in enzymology attracted Miller to the program, the welcoming community made IPiB stand out from other programs she considered. “I thought that I’d stay in California, where I’m from,” says Miller. “But after I visited, I knew I’d be moving to Madison.” During her time in IPiB, Miller served as the Outreach Chair for the Graduate Leadership and Development Committee (GLDC).
After graduating, Miller intends to return to California and continue exploring enzymology.
To learn more about Miller’s research, attend her Ph.D. defense, “Catalytic and binding mechanisms of histone H3 lysine-9 and lysine-36 methyltransferases” on Thursday, August 17, 2023 at 1:00 p.m. CT in Room 1211 of the Hector F. DeLuca Biochemical Sciences Building.