Emily Ma ‘20, Biochemistry: Making Moves in Sperm Cell DNA Folding
This article is part of the ongoing Senior Thesis Spotlight series.
How can two meters' worth of genetic information go from being packaged in one cell to another at least six times smaller in size?
Biochemistry student Emily Ma ‘20 explores this question and many others in her senior thesis in the Carter Lab, using a fish model to research how the protein protamine replaces histones located on DNA to produce even tighter loops that can fit into sperm cells. In a non-reproductive cell, genetic material is coiled by histones, proteins that attach onto DNA. During the formation of a sperm cell, however, DNA must be packaged significantly tighter to fit inside the protective sperm head, allowing the sperm cell to swim towards and fertilize eggs. The ability for DNA to fit within the sperm cell is made possible by replacing histones with protamine, which compacts DNA 10 times tighter than histones. Despite protamine’s importance in the creation of healthy sperm, little is known about the transitional process by which this protein interacts with and replaces histones, prompting Ma to base her thesis on this lesser-known topic.
Cartoon depiction of a DNA molecule tethered to a particle and a coverslip
Although DNA is too small to be viewed under a light microscope, Ma accomplishes her thesis goal with a process known as Tethered Particle Motion. One end of a DNA molecule is attached to “something we can see— a round particle that’s 1/50th the diameter of your hair— and the other end to a coverslip.” When placed in water, the particle will move due to being bombarded by water molecules but is held in place by the DNA attached to the slip, behaving similarly to a “dog tied to a pole”. According to Ma, “tracking how far the particle can travel from the center point tells us how much the DNA has folded”, with the addition of histones or protamine further limiting movement.
Ma’s path to her senior thesis began in her childhood and teenage years, leading to the moment where she could perform research of her own. As the daughter of a chemist, Ma spent countless hours visiting her father’s lab and listening to his lectures, awed by his passion for chemistry. Her high school’s science club would eventually provide an outlet through which Ma could first experiment with research, from “balsa bridge building to starting a beef jerky business to constructing a cardboard boat”. By the time she entered college, Ma had her mind set on conducting research and participated in Prof. Ashley Carter’s lab through Amherst’s SURF program after freshman year, a group she has been a member of ever since.
Despite the rigorous hours spent in and out of the lab, Ma’s research on DNA folding has future implications for fertility treatments, a cause she finds meaningful. As Ma notes, “A high proportion of sperm produced by infertile males have abnormally large sperm heads… [suggesting] that DNA packing may play a role in infertility.” She goes on to state that developing a greater “Understanding [of] how protamine replaces histones on DNA—a process crucial for passing on genetic information—could improve treatments that help couples have children.”
When asked to provide advice for others who may be interested in writing a thesis, this was Ma’s response:
"Before you decide on a thesis, I would recommend talking to other thesis writers,
especially the ones who are in the lab you’re interested in… Also, I would recommend
taking a hard look at your reasons for wanting to write a thesis. You need an answer that will sustain you through the inevitable disappointments and setbacks throughout the year and carry you to the finish line!"