Uncovering the mysteries of milk

Sarah Nyquist got her first introduction to biology during high school, when she took an online MIT course taught by genomics pioneer Eric Lander. Initially unsure what to expect, she quickly discovered biology to be her favorite subject. She began experimenting with anything she could find, beginning with an old PCR machine and some dining hall vegetables.

Nyquist entered college as a biology major but soon gravitated toward the more hands-on style of the coursework in her computer science classes. Even as a computer science major and a two-time summer intern at Google, biology was never far from Nyquist’s mind. Her favorite class was taught by a computational biology professor: “It got me so excited to use computer science as a tool to interrogate biological questions,” she recalls.

During her last two years as an undergraduate at Rice University, Nyquist also worked in a lab at Baylor College of Medicine, eventually co-authoring a paper with Eric Lander himself.

Nyquist is now a PhD candidate studying computational and systems biology. Her work is co-advised by professors Alex Shalek and Bonnie Berger and uses machine learning to understand single-cell genomic data. Since this technology can be applied to nearly any living material, Nyquist was left to choose her focus.

After shifting between potential thesis ideas, Nyquist finally settled on studying lactation, an important and overlooked topic in human development. She and postdoc Brittany Goods are currently part of the MIT Milk Study, the first longitudinal study to profile the cells in human breast milk using single cell genomic data. “A lot of people don’t realize there’s actually live cells in breast milk. Our research is to see what the different cell types are and what they might be doing,” Nyquist says.

While she started out at MIT studying infectious diseases, Nyquist now enjoys investigating basic science questions about the reproductive health of people assigned female at birth. “Working on my dissertation has opened my eyes to this really important area of research. As a woman, I’ve always noticed a lot is unknown about female reproductive health,” she says. “The idea that I can contribute to that knowledge is really exciting to me.”

The complexities of milk

For her thesis, Nyquist and her team have sourced breast milk from over a dozen donors. These samples are provided immediately postpartum to around 40 weeks later, which provides insight into how breast milk changes over time. “We took record of the many changing environmental factors, such as if the child had started day care, if the mother had started menstruating, or if the mother had started hormonal birth control,” says Nyquist. “Any of these co-factors could explain the compositional changes we witnessed.”

Nyquist also hypothesized that discoveries about breast milk could be a proxy for studying breast tissue. Since breast tissue is necessary for lactation, researchers have been historically struggled to collect tissue samples. “A lot is unknown about the cellular composition of human breast tissue during lactation, even though it produces an important early source of nutrition,” she adds.

Overall, the team has found a lot of heterogeneity between donors, suggesting breast milk is more complicated than expected. They have witnessed that the cells in milk are composed primarily of a type of structural cells that increase in quantity over time. Her team hypothesized that this transformation could be due to the high turnover of breast epithelial tissue during breastfeeding. While the reasons are still unclear, their data add to the field’s previous understandings.

Other aspects of their findings have validated some early discoveries about important immune cells in breast milk. “We found a type of macrophage in human breast milk that other researchers have identified before in mouse breast tissue,” says Nyquist. “We were really excited that our results confirmed similar things they were seeing.”

Applying her research to Covid-19

In addition to studying cells in breast milk, Nyquist has applied her skills to studying organ cells that can be infected by Covid-19. The study began early into the pandemic, when Nyquist and her lab mates realized they could explore their lab’s collective cellular data in a new way. “We began looking to see if there were any cells that expressed genes that can be hijacked for cellular entry by the Covid-19 virus,” she says. “Sure enough, we found there are cells in nasal, lung, and gut tissues that are more susceptible to mediating viral entry.”

Their results were published and communicated to the public at a rapid speed. To Nyquist, this was evidence for how collaboration and computational tools are essential at producing next generation biological research. “I had never been on a project this fast-moving before — we were able to produce figures in just two weeks. I think it was encouraging to the public to see that scientists are working on this so quickly,” she says.

Outside of her own research, Nyquist enjoys mentoring and teaching other scientists. One of her favorite experiences was teaching coding at HSSP, a multiweekend program for middle and high schoolers, run by MIT students. The experience encouraged her to think of ways to make coding approachable to students of any background. “It can be challenging to figure out whether to message it as easy or hard, because either can scare people away. I try to get people excited enough to where they can learn the basics and build confidence to dive in further,” she says.

After graduation, Nyquist hopes to continue her love for mentoring by pursuing a career as a professor. She plans on deepening her research into uterine health, potentially by studying how different infectious diseases affect female reproductive tissues. Her goal is to provide greater insight about biological processes that have long been considered taboo.

“It’s crazy to me that we have so much more to learn about important topics like periods, breastfeeding, or menopause,” says Nyquist. “For example, we don’t understand how some medications impact people differently during pregnancy. Some doctors tell pregnant people to go off their antidepressants, because they worry it might affect their baby. In reality, there’s so much we don’t actually know.”

“When I tell people that this is my career direction, they often say that it’s hard to get funding for female reproductive health research, since it only affects 50 percent of the population,” she says.

“I think I can convince them to change their minds.”