The E. coli lac operon is featured as the paradigm for prokaryotic gene regulation in our Biology 1510 Introduction to Biological Principles course. I want my students to learn the following key concepts):
- gene expression is regulated by proteins (transcription factors) that bind to specific sites on DNA to either repress or activate transcription;
- RNA polymerases initiate transcription at specific sites in the DNA called promoters;
- prokaryotic genes that function in the same pathway are often organized into operons, where all the genes in the operon are transcribed from a single promoter into a single mRNA molecule that is translated to produce multiple proteins.
Unfortunately, in 25 years of teaching Intro Biology and sophomore-level Genetics courses, I found that even after repeated textbook reading and lectures on the topic, many students have trouble answering questions such as:
If a mutation eliminates the CAP protein binding site, then the E. coli lac operon
- a) will be fully induced whenever glucose is present, regardless of lactose
- b) will be fully induced whenever glucose is absent, regardless of lactose
- c) will be fully induced whenever lactose is present, regardless of glucose
- d) will be fully induced whenever lactose is absent, regardless of glucose
- e) will never be fully induced
A few years ago, rather than lecture yet again about the lac operon, I devised and staged the Lac Operetta, where student volunteers act out the parts of the RNA polymerase, Lac Repressor, and CAP. The actors also sing short ditties, and the chorus (all the other students in the lecture hall) sings the refrain.
I thought that students would be able to conceptualize how the lac operon works if they thought of the different key proteins as characters with assigned roles. I also observed that many people have amazing memories for music. People have passed on stories and knowledge through song from pre-literate times. And getting students to participate by singing would break the usual class routine, and could further serve to stick the lesson in their memories. Oh, and I use props: Milky Way bars to represent lactose, any hard candy for glucose, and Red Hots for cyclic AMP.
You can click on this link to download my powerpoint: lac operetta_presentation
I ran the Lac Operatta for 3 years, immediately after a 30-min lecture on prokaryotic genomes and gene regulation. My wife also staged it in her freshman biology class at Clark-Atlanta University (before they fired her from her tenured position). It’s always lots of fun, and students remember this class years afterwards. But does it actually enhance their understanding beyond what I present in lecture?
This year, as part of my flipped class, students were asked to view the lecture video before class.
In class, I did an assessment of whether the Lac Operetta increased student understanding of the lac operon model. I used 4 of my standard test & clicker questions, and polled the class with clickers both before and after the Lac Operetta. At the start of class, I polled all 4 questions and collected the answers without comment. Then I sprang the Lac Operetta on them, and then polled the same questions again, in the same order. Students were free to discuss the questions with each other, both times the questions were polled, as per the usual procedure with clicker questions in my class.
Q1: Under which conditions will E. coli cells express (transcribe and translate) lots of beta-galactosidase?
- a) In medium with glucose as the only sugar
- b) In medium with glucose and lactose
- c) In medium with lactose as the only sugar
- d) In medium with galactose
- e) All of the above
This first question is a lower-order factual recall question, to see whether students have done the assigned reading or viewed the lecture video before coming to class. The histogram of the student clicker responses are shown below, with the pre-Operetta response percentages on the left in blue, and the post-Operetta response percentages on the right in red, for each answer choice:
At this point I was feeling pretty smug. Then I got to a much higher-order question:
Q2: If the repressor gene is mutated, so that no repressor protein is made, then
- a) The lac operon will never be induced
- b) The lac operon will always be induced
- c) The lac operon will be induced whenever lactose is present
- d) The lac operon will be induced whenever glucose is absent
- e) The lac operon will be induced only when both lactose and glucose are present
Now I was shocked and devastated. My efforts with the Lac Operetta staging had apparently strengthened a misapplication of the model. But instead of correcting them, I asked them to discuss with their peers again, but also to think about what they had just seen in the Lac Operetta, and think about what the Repressor and Cap did. And I repolled.
The repolling showed a dramatic change, so that now the majority chose the best answer. I like to think that perhaps students had first thought of the Lac Operetta as mostly entertainment, but then realized that it could be used to think through how the lac operon model actually works.
Q3: What causes induction of the lac operon?
- a) When Repressor binds to the operator, regardless of CAP
- b) When CAP binds to the promoter, regardless of Repressor
- c) When Repressor binds to inducer
- d) When both a) and b) occur
- e) When CAP binds to the promoter and Repressor is not bound to the operator
Q4: In wild-type E. coli cells in medium with glucose, and no lactose:
- a) CAP binds to promoter
- b) Repressor binds to operator
- c) Both CAP and Repressor bind to promoter and operator, respectively
- d) Neither bind
The last two questions showed the highest percentages of correct responses to these questions than I had ever seen, posed either as clicker questions or exam questions. Questions #3 and #4 are not as difficult as question #2, but clearly viewing the Lac Operetta and then applying it helped many students to work out the correct answer.