Bailey Walker: Communication is key—How examining genes within the cumulus-oocyte complex can result in more successful pregnancies

The following story was written in May 2020 by Lilly Savin in ​ENGL ​4824​: Science Writing ​as part of a collaboration between the English department and the Center for Communicating Science.

Now more than ever before, humans rely on alternative methods to achieve pregnancy. Yet techniques such as in vitro fertilization (combining an egg with sperm outside of the body) are expensive and unreliable. How do we ensure that potential mothers aren’t gambling their time, money, and health on unsuccessful pregnancies? This is a question Bailey Walker, a second year Ph.D. student studying developmental biology and genomics at Virginia Tech, wants  to answer.

    Originally from Wichita, Kansas, Walker received her bachelor’s degree in chemistry from Wichita State University before transferring to Auburn University to pursue another bachelor’s degree in animal science. It was there that she discovered her love for research and started a master’s degree project with her advisor, Dr. Fernando Biase. When he moved to Virginia Tech and offered her a Ph.D. student position instead of finishing her master’s degree at Auburn, Walker made the decision to move, too.

    “This was never planned,” Walker says. “I never thought about Virginia Tech, it just kind of fell into my lap.”

    Now Walker spends most of her time in Litton-Reaves Hall, where she conducts her research. Her studies center around the cumulus-oocyte complex (COC), a cluster of cells (called cumulus cells) surrounding and nourishing an oocyte, or egg, and located in the ovary.

    Walker categorizes oocytes into two groups for her research: fully grown (good quality) and still growing (bad quality). Good oocytes are ready to ovulate and be fertilized, while bad oocytes aren’t fully grown.  

    What determines if an oocyte will be fully grown, or able to develop successfully into a living human being?

    Walker hypothesizes that the answer to this question lies within the “communication” between the cumulus cells and the oocyte—the shared genes among the two cells.

    “All cells in the body communicate with other cells,” says Walker. “Proper communication in the COC should result in the oocyte successfully growing while still in the ovary, ovulating out of the ovary, and being fertilized successfully by sperm.”

    But what does this “proper communication” look like? This question remains unanswered, but by studying the COC at the gene level, an answer could potentially be found.

    To begin her research, Walker receives cow ovaries bought from slaughterhouses. After the ovaries are delivered to Litton-Reaves, she dissects the ovaries and retrieves the desired cells, using a microscope to help her find them. Once she finds cells suitable for her work, she dyes the cells with a stain called “brilliant cresyl blue.” The stain helps detect cell maturity: bright blue indicates a mature cell, while no color indicates an immature cell. This is how she identifies “good” and “bad” oocytes.

    After extracting RNA from the cells, her work turns primarily to her computer as she analyzes data using software packages such as Linux and RStudio. She looks for three things during her research: the genes that the two cells have in common, the genes unique to the two cell types, and the genes that differ between good and bad oocytes.

    Then she begins verification studies, putting the mature and immature cells through the entire process of in vitro fertilization—the same pricey and, oftentimes, unreliable method many women rely on to achieve pregnancy.

    She lets this process continue until the cells develop eight days into the blastocyst stage of development. From there, she determines whether the mature cells develop more blastocysts than the immature cells (or vice versa). Blastocysts are considered good quality embryos and should yield the highest pregnancy rates when transferred back into the mother. However, even at that stage success is not guaranteed.

    “It’s a lot of work happening at the same time,” Walker says. “Sometimes it can get jumbled in your mind because you’re doing a lot of hands-on work. It takes quite a while to develop that mentality of seeing the end picture.”

    And for Walker, that end picture is temporarily on hold. During the coronavirus pandemic, the only research permitted at Virginia Tech is that directly studying the coronavirus or research that, if halted, would directly lead to animal and human death.

    “Neither of those categories applied to my research, so [it] had to completely stop,” she states.

    Walker has found other ways to keep herself busy. She’s shifted her focus to computational work, analyzing more data through RStudio and creating the visual data that she’ll eventually need.

    Despite the obstacles she faces, Walker remains hopeful that she’ll eventually prove her hypothesis correct—that the gene networks existing between the oocyte and the cumulus cells at an immature phase will be present, but different from the cumulus cell and oocyte that are labeled as more mature.

    “What genes present within the COC define good or bad communication?” Walker asks. “By answering this question, we hope to improve techniques used in vitro fertilization so that it is a much more reliable system resulting in more successful pregnancies.”

    But Walker’s contribution to solving this issue doesn’t just have the potential to help mothers looking to start a family.

    “Animals that we rely on for our food supply are very often bred through artificial means,” she states. “So, without success we will lack food, and our food supply already has to increase every single year to accommodate our growing population.”

    And progress looks hopeful, as the first phase of her study involving the blue stain is already complete. Once her research is given the green light to continue, she plans to begin her verification studies, performing gene knockdowns on genes deemed significant. Gene knockdowns reduce the expression of certain genes so that researchers are able to test what they do when they’re turned off.

    Walker plans to conduct another study, which will wrap up by May of 2022 when she defends her dissertation.

    “But all work, when it’s finished, leads to something else,” Walker says. “[Dr. Biase] will continue this project while I move on, and he’ll bring someone else in to study it next.”

    It is without a doubt that whoever that is will have big shoes to fill.