Reading scientific papers

The ubiquitin multi-motif protein UHRF1 is a central player in targeting repressive chromatin marks. It contains a SRA domain, which binds to hemimethylated DNA, a Tudor domain binding to methylated H3 (H3K9me3) and a PHD finger interacting with an unmodified arginine residue within H3 (H3R2) [72–74]. Furthermore, UHRF1 interacts with DNMTs, G9a and HDAC1 and thereby unites various enzymes that can provide a repressive chromatin environment [75–77]. Interestingly, UHRF1 also recruits the H2AK5 actetyltransferase TiP60 thus integrating a multitude of different epigenetic signals [78]. A further example for the link between DNA methylation and histone modifications represent methyl C binding proteins such as MeCP2, which interact with co-repressor complexes including HDACs and HMTs [79,80]. Interestingly, a recent report shows that components of the piRNA pathway are required to target de novo DNA methylation to an imprinted region of the mouse genome implicating that selective methylation of imprinted regions can be regulated by non-coding piRNAs [81].

Imagine 21 pages of this. Okay, 9, if you discount the bibliography. That's the review article we're supposed to read (and understand) for the final part of the Epigenetic Control of Gene Expression MOOC at Melbourne University.

Well… I'm finding it a lot of work to read the text, parse the sentences, expand the abbreviations, and finally integrate it into a whole. I suppose it's mostly due to a lack of training − if I were to read that kind of paper on a daily basis, I guess I would acquire some paper-reading skills. That, or my brain would overheat and melt (and believe me, it's embarrassing to have to mop up your own liquefied brain matter that's dripped through your ear ducts to the carpet.)

I guess I'll have deserved that certificate.

Notes from the trenches: Epigenetics at Melbourne

[ed: it's been a while since I've posted, mostly because not much happened.]

While it's officially Week 5 in a 7-week course, I'm actually well into Week 6 (weekly content is released a week in advance), with only one quiz to take − I expect to do it later today − then it's down to the dreaded peer-reviewed essay.

All this to say that I feel capable of discussing the course.

(to digress, there's something I thought about yesterday: MOOCs are supposed to be “communities” for students, but they are transient − lasting only a handful of weeks. For the same reason it's hard to be able to discuss a course in general terms based on only a couple of weeks' content, it's difficult to get to know people − fellow students − in such a short time. I wonder if multiple-course sequences, like the ASTROx year-long series at ANU, will actually foster such a “community”.)

Anyway − epigenetics is the study of the process through which genes are stably turned on or off. The keyword here is “stably” − while a given cell will express genes differently at various times (for instance insulin secretion is turned up when glucose enters the pancreatic beta-cells), this is not an epigenetic change; rather, some genes are permanently turned off (or on) for the whole life of the cell, barring exceptional circumstances, and this state is preserved when the cell multiplies.

Something which the course makes very clear is that this is a field under active research. In other words, there is very little that we know for certain − some processes are well-understood, but most are not, and a large part of what is thought is “very controversial”, that is to say, researchers disagree strongly on how the mechanisms work, and even on whether they actually exist in the first place. So that's pretty exciting, if somewhat confusing: one doesn't quite expect to walk into a classroom and be told “okay, so we think there is some epigenetics here, but we're not sure, and we don't really know how it works anyway, so if you're thinking of doing some research of your own in the future, that's not a bad place to start.”

In keeping with this bleeding-edge focus, the course places a strong emphasis on reading scientific papers, over at PMC or PLOS − we're actually quizzed on the papers. In a way, the video lectures are only an introduction, the real meat of the course being the papers. That's the hardest part for me: reading and understanding jargon-laden, dry papers is a specific skill that I, erm, need to work on (I find my eyes glaze over pretty quickly). It's also not an activity that can easily fit into my normal MOOCing times (on the bus/train? No way, requires much more concentration − in the evenings? Nope, requires a freshness of mind that I just don't have after a full day's work − ideally I'd get up an hour earlier and read during breakfast, but er… I value sleep, too).

In terms of content: the first few weeks are about the well-understood mechanisms (DNA methylation, chromatin structure and histone modifications, X chromosome inactivation, epigenetic reprogramming), then we get on to more controversial topics (environmental disruption of epigenetic state, for instance the effects of tobacco smoke, or diet, at crucial periods of time). The last week of the course is about cancer, which is pretty interesting (epigenetic modifications are one of the hallmarks of cancer − it's actually one of the very few common points of all cancer types: not knowing anything about the subject, I'll refrain from qualifying cancer as an “epigenetic disease”, but it's certainly tempting.)

The lectures are basically slides with an embedded shot of the lecturer (Marnie Blewitt from Melbourne University) in the corner. While I usually dislike this format, here it works well, partly because Dr Blewitt is a great speaker with a clear voice, but mostly because the slides are only outlines / supporting material for the course itself. In fact I find I hardly read the slides − I just skim them and concentrate instead on the audio.

Every week there's a quiz, which is fairly difficult − you have three tries, but the questions change between each try. As I said, the quizzes are often about specific points raised not in the lecture, but in the required readings, forcing us to read the papers, not a bad thing. At the end of the course, there is a peer-reviewed essay; I'm not certain how it will play out, it's been ages since I wrote essays (and then again, never in a scientific subject). I'll keep you posted about how it turns out.

So, in general, I like this course quite a lot, and it's certainly given me a lot of things to think about.

Just starting: Epigenetic control of Gene Expression, at Melbourne University

So there's a new MOOC over at Coursera starting up today.

Why take this MOOC?

Because I really liked the genetics part of MIT's 7.00x Introduction to Biology, and wanted to learn more. Someone on the forums there pointed to this course, and here I am.
Plus, I'm kind of in an Australian mood, what with the Astrophysics course at ANU.

What's epigenetics anyway?

It's the study of how protein synthesis (from DNA by way of RNA) varies, between individuals, between cells in a specific individual, and at different points in time for a specific cell, without changes to the actual genome (the DNA sequence).
Basically that's why monozygotic twin cats may have completely different colours.

Sounds complicated.

That's right. Though you may spell it "fun".
I guess that'll be the real test, whether the instructor (Dr Marnie Blewitt) can make it easily understood. Based on the first 2/3rds of the first week's lecture, I'd say she does a good job of presenting the subject matter in an organized way that conveys the important information in a digestable package.

Right; let's go!