Katie Dickinson
This post is by UW research scientist Katie Dickinson
“It was through the [Bio180 CURE] class that biology truly came to life and I felt that our time in [the] lab was interesting and relevant to our world today. The large lecture halls felt smaller as our table group grew closer together…” Former Bio180 CURE student.
I am helping to develop a set of labs that enables undergraduate students, early in their academic career, to experience what it is like to do research. Ultimately, we aim for this CURE (Course-based Undergraduate Research Experience) to be woven into the Introductory Biology series (BIOL 180 and BIOL 200) at the University of Washington. In addition to trying to make research accessible to large numbers of students, students are able to observe evolution in action to better understand a global health crisis, antibiotic resistance.
In this blog I wanted to provide a general overview of the Intro Bio CURE lab series. Students use bacteria to investigate the evolution of antibiotic resistance at the population level and connection to cellular/molecular mechanisms.
Students hard at work
In the first set of labs, students expose E.coli to specific drug regimes, which select for resistant mutants. These mutants, along with a sensitive ancestor, are transferred daily in drug-free media for several weeks. Samples of each isolate are frozen down enabling students to make comparisons between the progenitors (from the beginning of the transfers) and the descendants (from the end of the transfers). Then assays are done to determine competitive fitness and the level of drug resistance of each isolate. The resistance level will be measured in two drugs enabling students to gauge whether they see evidence for cross-drug interactions; where resistance to one drug (the drug in the Petri dish that was used to isolate the strain) confers increased or decreased resistance to another drug. These labs highlight evolutionary phenomena at a population level.
Alumni students assisting with lab prep
In the second series of labs, students will analyze the products of their own evolution experiments (evolved bacterial isolates from the first course). Activities include: PCR/gel of a candidate gene, DNA sequence analysis, exploring protein sequence and structure analysis. The goal is to enable students to trace genotype to phenotype at the cellular level, and connect evolution to molecular biology.
Experimental Overview Schematic
| Lab | Activity | Key Concepts |
| Lab1 | Screen for resistance by spreading a sample of bacteria on Petri dishes with antibiotics and without. | Natural selection, mutations, antibiotic resistance, sterile technique |
| Lab 2 | Pick resistant mutants (and a sensitive isolate as a control), freeze down a sample and begin serial transfers in the absence of drug. | Experiment design, fitness, the cost of drug resistance, evolution and population dynamics
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| Lab 3 & 4 | Calculate relative fitness with mock data, learn how to determine a minimal inhibitory concentration (MIC) value, use R/Rstudio to graph and gauge significances. Serial transfers continue. | Basic statistics, graphing, introduce cross-drug interactions (collateral sensitive/resistance) |
| Lab 5 | Serial transfers end. Competition and MIC assays comparing the progenitors to their descendants | Relative fitness, Levels of drug resistance, importance of collaboration |
| Lab 6 | Data analysis, suggest future research | Data interpretation, determine if there is evidence for a fitness cost associated with resistance, compensatory mutations, reversion, look for collateral effects |
| Lab 7 | PCR, gel electrophoreses, sequencing | Central dogma, genetic techniques |
| Lab 8 | Analyze sequencing data | DNA sequence analysis, identify mutations, translation, evolution, genotype |
| Lab 9 | Protein structure | Resistance mutation effect protein structure, enzyme function, phenotype and fitness. |
| Lab 10 | Poster presentation | Integrate connection between genotype, phenotype, and fitness. Scientific communication, collaboration |
Competition Petri dishes and MIC microtiter plates
Last year we ran several pilot classes (single lab sections with 24 students). This winter quarter we scaled up, four randomly selected BIOL 180 lab sections swapping out the tradition lab material for the CURE modules. Currently, three BIOL 200 sections are continuing the CURE labs this spring quarter. Throughout the Intro Bio CURE labs, students are collaborating and communicating to collect and analyze their own data and propose follow-up experiments. In addition, students are introduced to career-transferrable skills.
Presently, data is being gathered on student outcomes. We are specifically measuring: core concepts, competencies, and affect. Are students gaining a better grasp of evolution via natural selection? Are they able to connect genotype to phenotype to fitness? Is there evidence for improved understanding of the experimental process, and how to gather and interpret data? Do students gain an appreciation for the importance of data visualization, statistics, scientific communication & collaboration? Does the Intro Bio CURE series enhance a sense of belonging in science/college and does this translate to retention in STEM fields? Do students identity as scientists? Are we successfully enabling students to cultivate a positive attitude towards value of research and practice of science?
What is next?
If outcomes are looking promising, we plan to go forward with scaling. By winter 2019 all students enrolled in the UW Introductory Biology series will be provided with the opportunity to engage in authentic research experience, serving roughly 2000 students per quarter!
