Deepkiran Singh, a UW junior in biochemistry, demonstrates pipetting, a lab technique to measure or transfer liquids.
UW undergraduate Randy Lu grasps a pair of tweezers in each hand. His fingers make imperceptible movements as he dissects the tiny abdomen of a fruit fly. The tweezers and Lu’s hands look garishly large next to the insect, which is a mere speck in a glass dish. Lu has to look through a microscope in order to see it in detail.
Leaning over Lu’s shoulders is his mentor and fellow undergraduate Debra Del Castillo, who guides him as he learns how to master the light touch necessary to complete such delicate work. Lu is not the first student Del Castillo has mentored: As program coordinator for an undergraduate research project that brings students into the lab of UW biochemistry professor, Hannele Ruohola-Baker at UW Medicine’s Institute for Stem Cell and Regenerative Medicine Research. Del Castillo has overseen the work of dozens of students for the past two years.
The students contribute to an ongoing study examining a protective signal daughter cells send back to their stem cells in the germ line of fruit flies. The signal seems to help the stem cells survive even when they are targeted with chemotherapy or radiation. Researchers believe this phenomenon could explain why some cancers are so difficult to eradicate.
To combat this, researchers are screening nearly 1,600 different molecules to see if any prevent the daughter cells from sending that signal. Molecules that do this could be turned into a drug that would prevent tumors from regenerating.
The screen is an intensive process composed of multiple steps—a perfect opportunity, Del Castillo feels, to teach undergraduates how real-world science often works.
Debra Del Castillo teaching in an ISCRM lab
Debra Del Castillo looks through a confocal microscope to check undergraduate Randy Lu’s progress dissecting flies.
lab teaching confocal microscope
“Most undergraduate programs have labs where the experiments are highly optimized, where you know what the results are going to be,” she said.
Ruohola-Baker testified to the explorative nature of the work students partake in.
“You are the first one in the world to find the answer for your question when you come in the morning to develop that film, study those stem cells in the confocal microscope or analyze their level of RNA after the drug treatment,” she said. “Your job is to go to the edge of human knowledge and push beyond.”
The step-by-step process looks like this: Students feed one of the small molecules in question to a days-old fruit fly, then sacrifice the insect, isolate the affected cells and put them through a lengthy immunohistochemistry protocol. Next come dissection and analysis to determine whether or not the molecule interfered with the protective signal. Students are usually trained for three to four months before they are allowed to complete the process on their own and analyze results.
“I have to work with them a lot to get the confidence to make that call, because they’re young and they’ve never done this before, and they’re afraid they’ve done it wrong,” Del Castillo said.
She, too, had to develop confidence when she first joined the project. Currently a post-baccalaureate studying biochemistry, she took a winding path to get where she is now: A degree and then a job in engineering, followed by many years of caregiving, first for her children and then for her aunt, who was diagnosed with Huntington’s disease.
“It all ended at once; I went from caregiving to nothing, so I thought I’d go back to school,” she said. “In high school, I had wanted to be a doctor or medical researcher, but because I came from a family where all these strange things happened—my mother died at 27, my grandmother got schizophrenia at age 50—I didn’t feel like I had the support to go for it when I was young.”
She eventually found out that Huntington’s runs in the family. She was tested and does not carry the gene. That knowledge spurred her to pursue medical research. She wants to do studies that might lead to new ways to protect other people from disease. At North Seattle College she fell in love with cellular biology and organic chemistry. There she participated in her first research project, an experience that ultimately inspired her to bring undergraduates into the lab at UW.
Currently, 14 undergraduates are involved in the study; each works up to 25 hours a week. One student, biochemistry junior Deepkiran Singh, wants to become a gynecological surgeon and feels contributing to research helps her prepare for that goal.
“Working with your hands, being precise, is really important,” she said. “Before, I was shaky; I had to learn. And it’s good to have lab experience when you go into medicine. I have more of a sense of freedom here [than in a classroom].”
Del Castillo believes the work will have lasting effects on students.
“Young people spend so much time in school, but this really prepares them for real-world jobs,” she said. “To see the principles of science and biochemistry at work is so profound: It sets the stage for them to have a realistic understanding of what it takes to get valid, reproducible results and to do good science.”