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The Levinson Emerging Scholars Program

Derek Britain - Biochemistry, Bioengineering

Derek Britain Derek Britain is a senior in the Departments of Bioengineering and Biochemistry. He got his first exposure to research his freshman year when he joined Dr. Deok-Ho Kim’s lab in Bioengineering. While there, Derek worked on creating a novel cell culture device that combined a nano-patterned substrate with a microfluidic gradient system for the organization of stem cells into cardiac tissue grafts. While testing his device, he became fascinated with how the stem cells were able to sense and respond to the substrate and chemotaxic gradient. Derek continued to pursue his interest, and at the start of his junior year join Dr. Roger Brent’s lab at Fred Hutchinson Cancer Research Center. Using budding yeast as a model organism, Derek now researches how cells gather information from their environment, how this information is processed by the cell, and how a cell makes a decision based on the results. Currently, he is investigating the role microtubule end binding proteins play in signal transmission and fidelity. Derek is also investigating mutant forms of these proteins found in the human population, and if these mutations result in poor signal handling that could result in poor cell decisions. After completing his undergraduate degrees Derek plans to further pursue his research in a Systems Biology PhD program.

Mentor: Roger Brent, FHCRC

Project Title: The effects of human variants of yeast Bim1 on signaling in the yeast pheromone response pathway

Abstract: The three mammalian MAPRE proteins (EB1, RP1, and EBF3) play important roles in the stability and localization of microtubules, and facilitate the binding of other proteins to microtubule plus ends. The 1000 Genomes Project and The Exome Sequencing Project have elucidated non-conservative coding sequence allelic variants of the MAPRE proteins in the human population. Disruption of MAPRE protein function could decreases signal fidelity and microtubule function, leading to poor cell decision making and mitotic chromosome separation. The MAPRE proteins are related by descent from a common ancestor to the Bim1 protein in budding yeast. By designing and building mutated versions of Bim1 that contain mutations corresponding known MAPRE allelic variants and expressing them in yeast, we hope to elucidate the effects of the MAPRE polymorphisms. In particular, we will observe changes in signaling fidelity in the yeast pheromone response pathway. Budding yeast will be exposed to a linear gradient of mating pheromone, and various florescent reporters will be monitored through live-cell epi-fluorescent and FRET microscopy. Florescent signals will be quantitatively analyzed to determine protein abundance, indicating the degree to which signal fidelity has been affected. Adverse effects on signal fidelity can result in poor decision making and environmental response, potentially leading to the generation of disease. By better understanding the effects of allelic variants in the human population, we will be able to develop individualized health plans and therapies.