I got all the way to Epigenetic regulation of the genome and that was it.
One thing I’ve wondered about and your community representatives may also is how do you determine how many animals you need for each experiment. Too few renders your statistics irrelevant and too many is expensive and mean.
“an epigenetic modification which is important in the regulation of gene expression and chromosomal instability”:
–Methylation of DNA is a natural epigenetic modification–
“a class of proteins called DNA methyltransferases; both humans and mice have three such genes”:
what is “such genes” referring to?
–a class of proteins called DNA methyltransferases produced by (certain genes); both humans and mice have three such genes–
Except that only some of the people on the committee are non-biologists; this is the only section where we describe the aims of the research, so it has to be “correct” enough to pass muster with the specialists as well. I think this is a stupid arrangement, but I don’t get to rewrite the form.
The part that really annoys me is that the other thirty pages of the protocol, where we describe in ghastly detail the horrible tortures we will perform on the innocent little mice, passed with only two minor comments that took all of 30 seconds to fix.
That’s an entirely different four-page section of this effing mess. Basically we:
1. work out how many mice we will need to have reasonable statistical power for one experiment (which varies with the type of experiment, the failure rate of the techniques involved, the amount of biological variation we expect to see in the system, and a number of other things),
2. figure out how many mice we will need to breed to get that many experimental animals (since we only want certain genotypes, and depending on the genes involved and how the breeding is set up they may be produced at a rate of anywhere from 1/2 to 1/16 of pups born),
3. multiply by the number of experiments we plan to do in the next three years,
and then (since they actually count each individual mouse we use as we go along, and if we run out we have to write a new protocol to get more),
4. come up with a plausible-sounding reason to ask for 1.5x or 2x that many mice.
Since our experimental plans will almost certainly change in the three-year protocol period, the number of mice we request in the protocol has only a very tangential relationship to the number of mice we will actually use, but for obvious reasons we don’t emphasize this point.
Boyo Jim, Little Nemo, your versions were excellent (aside from being factually incorrect ), and I may crib the next draft from one or both of you. j666, I like your structure but I don’t think the Committee will like having the definitions separated from the text. I’m due to have a chat with one of the administrative persons about this section this afternoon, and I’ll see what they have to say about the idea.
It’s so common in my industry, I thought the FDA required it. I could check 210/211, but I’m off for the week.
OK, I scanned 210/211 and 820; I find no requirement for definitions, BUT the FDA puts definitions at the beginning, right after the scope of the regulation.
Although it’s neat to learn these definitions, I was trying to point out the things I didn’t understand, so that you get an outside perspective on what somebody who doesn’t know the subject matter might not understand. In other words, these are the things I think you might want to elaborate just a bit more on (or clarify) if you’re going to leave them in. I also like the upthread suggestion of either leaving the specific terms out, or replacing them with more vague terms. It’d give a broader idea of the subject matter, and make the reader feel more intelligent (and more likely to approve of your proposal) because they’d understand all the words and “get it” during the first read.
I kept reading it, and I kept tuning it out. Of course I’d be trying harder if I were on your committee, and I feel I have a general idea of what the experiment is supposed to accomplish, but I know a whole hell of a lot of college educated laypeople who are pretty dumb. I think Little Nemo’s version is quite good.
(or at least I hope so), and cautious optimism now reigns.
No doubt motivated by utter desperation (they must be at least as sick of reading this thing as I am of writing it), a member of the Committee has suggested that we break the section into two parts, starting off with a simple summary for the [del]mouth-breathers[/del] honorable and respected community representatives, and then a more detailed explanation for the scientific members. I’ll spare you guys the technical bits (if what I’ve posted so far is Swahili, the technical summary would be Martian ); the nontechnical aims now read:
During normal embryonic development and in the development of disease states such as cancer, cells change the ways in which they use the various genes in the genome. These changes are stabilized and preserved by long-lasting but reversible processes known collectively as epigenetic regulation. Our research focuses on exploring the roles of certain genes which are known to be involved in epigenetic regulation (particularly Dnmt1, Dnmt3a, and Dnmt3b), both in embryonic development and in a type of brain cancer called medulloblastoma. To perform these experiments, we use two classes of genetically modified mice: a set of strains which allow us to control the levels of the genes we are studying in specific tissues, and strains which are predisposed to the medulloblastoma brain cancer.
The first aim of our study is to examine the effects of epigenetic regulation during embryonic development. We will breed animals in which the levels of the genes we are studying are reduced or eliminated in different tissues, and examine their development and patterns of gene usage.
The second aim in our study is to examine the roles of epigenetic regulation in tumor formation and growth. Many types of tumors show abnormal epigenetic regulation, and this is known to promote tumor formation and growth in animal models of cancer and in human cancers. We will cross our genetically modified mouse strains to produce tumor-prone mice in which the levels of our genes of interest are reduced, and examine tumor formation and growth in these mice.
(note that I’ve flipped the aims around compared to prior versions)
I’m slightly worried about using “gene levels” instead of “gene expression”, since the former could be confused with gene dosage, AKA copy-number variation, but I can’t think of a better term that is suitably simple.