Molecular Bio MOOC, part I: DNA copied while you wait

Course: Molecular Biology – Part 1: DNA Replication and Repair
Length: 8 weeks 4-6 hrs/wk
School/platform: MIT/edX
Instructors: Stephen Bell, Tania Baker

Do you feel like studying biology is just memorizing hundreds of protein names and functions? Wake up, and take a different approach with MIT Biology’s 7.28x. You’ll experience an approach to learning infused in experimental research with animations that make complex details come to life….
What you’ll learn:
• How to compare and contrast the mechanisms of DNA replication in prokaryotes and eukaryotes
• How to describe several enzymatic mechanisms that the cell uses to repair or tolerate DNA damage
• How to analyze protein structures to infer functional information
• How to design methods for the best experiment to test a hypothesis related to DNA replication or repair proteins
• How to interpret data from DNA replication and repair experiments

I have to smile when I see, on the sign-up page for this course, the estimation that it will take 4 to 6 hours per week. This is repeated in the introductory material: about two hours of video lecture, another hour of ungraded comprehension questions, and one to three hours for the weekly graded quiz. That might work for some people, particularly those familiar with the design and interpretation of lab assays. I probably spent more like 10 to 12 hours a week.

And every minute was worth it.

This is the first third of the MIT microbiology series, focusing, as the title says,on DNA replication and repair. Part 2 will cover transcription (starts in a couple of weeks), and part 3 will get into RNA translation. They all build on the 7.00x “Biology: Secret of Life” course I took earlier, and list it as a recommended prerequisite.

Most moocs include some kind of “goals and objectives” for each week; most are pretty abstract and not terribly useful. But the ones for these courses are different: they’re extremely helpful. The objectives serve as a blueprint for the quizzes. If it says “Predict the effect a disruption of telomerase function would have”, you can bet you’ll have to pick an assay result that shows the effect in a given situation. If an objective is “Analyze protein structure to infer functional information”, chances are good you’ll have to find a binding site that’ll work with a particular molecule. That objectives list is the study guide to the course. If you can handle that list, you’ve learned the material.

The lecture videos, diagrams, and short animations all serve to lay out a clear picture of exactly what happens at each stage of DNA replication and repair – including proteins involved, energy requirements, and what happens in the event of failure – but that’s only the beginning. What these courses do incredibly well is simulate lab conditions that illustrate these processes, which, by the way, are the means by which the picture of what’s happening is discovered and confirmed in the first place. This isn’t makework, it’s what biologists do. Obviously, mooc students aren’t going to be able to culture e. coli or obtain fluorescently labeled dNTPs or run gel electrophoresis, and to their credit they don’t try to substitute videos of people doing those things and call it a virtual lab. Instead, they write up a little multi-act play in the form of the weekly quiz:

You study Okazaki fragment DNA maturation and nucleosome assembly. Your advisor wants to understand how the lagging strand DNA polymerase decides to stop extending an Okazaki fragment. He asks you to test the hypothesis that Okazaki fragment length relates to nucleosome positioning in the budding yeast, S. cerevisiae. Your advisor’s hypotheses mainly focus on the lagging strand DNA polymerase.

The questions then go through a series of steps: your labmate Zoe asks a question about why you’re doing something one way and not another, and you have to pick the right rationale; you run this assay and get this result, what do you conclude; you decide to try a different angle, what assay do you want, what reagents do you need, and what result do you expect? When your labmate Brian (oh, dear Brian, poor never-quite-right Brian, beloved by all but trusted by none) runs the assay and gets a weird result, what’s the most likely thing he did wrong? When you get stuck, the more experienced Alice will be able to glance at your results and suggest a course of action, at which point you need to figure out what she’s correcting. It’s pretty ingenious to design a quiz like this, and even more so to design it so that no subsequent questions give away the answers to prior questions (trust me, I looked).

You can’t fake this course. Too many moocs are eminently fakeable; some day I’m going to see if I can get a good grade in a course without ever watching a lecture or reading anything, just by searching for answers in lecture transcripts or other online sources. But not here: you either know what you’re doing, and can put six different threads of information together into a picture of what’s going on in that particular DNA, or you can’t. Sometimes you can narrow it down a little, but that’s about it. What really freaked me out regularly is that, buried among seriously complex scenarios are some laughably simple questions. I kept thinking, This one must be a trick. No tricks, though. Just damn good test design. I don’t always feel like I’ve earned my grade in a mooc, but I sure did here.

For those who are more advanced, the course includes a “journal club” featuring current articles relating to the topics of each week. I wasn’t in any shape to participate, but it’s a great way to design in multiple levels. Maybe next time, I’ll be able to make use of it. Forums were active and helpful; I wish I’d been able to offer as much as I asked, but, again, maybe next time.

Every time I take a biology or anatomy course, I come away with a sense of awe. Awe, in the classic sense, is wonder mixed with dread or fear, a sense of being dwarfed by something so immense as to be nearly incomprehensible. It’s often applied to the beauties of nature: the Grand Canyon, the recent images of Jupiter brought to us by an exploratory vehicle launched six years ago. As amazing as those things are, they’re nothing compared to the billions – I don’t know, billions, trillions? – of separate, interrelated events happening in our bodies every second, events that we really have no control over, but that must take place in order for us to be here. The molecules keeping us alive make the Grand Canyon seem kinda small, if you ask me.

Jupiter’s still really cool, though. Maybe transcription or translation will dwarf that, too.


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