What They Learned: Hannah Doll ’21

The biology major studied zebrafish with an ap2s1 gene mutation who don’t respond to startling visual stimuli that mimic predators, but overreact to startling auditory stimuli.

Hannah Doll’s thesis topic emerged as a bit of an accident. When the pandemic began last spring, Doll, a biology major and chemistry minor, could not continue her in-person research. Instead, her thesis advisor, Assistant Professor Roshan Jain, suggested she analyze a collection of zebrafish data during the rest of the spring and summer remotely.

The data Doll analyzed uncovered an interesting puzzle. Zebrafish with a mutation in the ap2s1 gene did not react to startling visual stimuli that mimic approaching predators, but they overreact to startling auditory stimuli.

“This led us to ask if there was a perceptual issue–are they blind?–or if the mutation affected brain circuitry involved in making the decision to respond to the perception,” said Doll. “The lab is interested in how genes work in brain circuits to facilitate behavioral choice, so we set out to test these mutants in a number of other visual tasks to evaluate what they can see and if they choose different responses than non-mutants do.”

Doll’s research found that the ap2s1 mutants can see visual stimuli but respond to them very differently than non-mutants do.

“Sometimes in subtle ways, like in the kinematics of responses, and sometimes in dramatic ways, like a huge drop in responsiveness compared to non-mutants,” she said. “By comparing these results to what we know and what is reported in the literature, we have ideas for more experiments to get at the brain regions and the mechanisms involved in the function of this gene, ap2s1. This knowledge could be relevant to human conditions linked to this gene, as well as enhance our understanding of general neural mechanisms of decision-making.”

What did you learn from working on your thesis?
I learned about what it takes to set up and troubleshoot experiments that are brand new to a lab. Designing a protocol can be orders of magnitude more complex than following one; there are so many factors to consider in order to make sure you’re really getting at your biological question, from stimulus design to the toxicity of the glue used to assemble parts, to ordering the right computer for tracking and analysis. My biggest takeaway is that science goes beyond building expertise in a niche area; you also need to be attuned to the physical realities of things–to learn how your machines work, how to code, how to collaborate with folks in other countries. And that those things aren’t just barriers to answering your question, they contribute to a certain conscientiousness that makes answering those questions possible.

What are your plans for the future?
After graduation, I will be working in Dr. Bushra Raj’s lab at the University of Pennsylvania investigating how neural progenitors coordinate brain development. I plan to attend graduate school and pursue a career in research. Working on this project definitely helped me realize that I am really interested in neuroscience and that research is definitely something I want to pursue.

“What They Learned” is a blog series exploring the thesis work of recent graduates.