"College-educated lay person" Dopers: Help me out!

In My Humble Opinion
1

Preamble: I work in a biology research lab, and we are currently stuck in the paperwork hell of the three-year review of our animal use protocol. Part of this process is a review by our Institutional Animal Care and Use Committee to justify the use of live animals (in this case, mice) in our projects.

As this committee includes some “community representatives”, who are volunteers and non-biologists, there is a mandatory section with the requirement to:
"Using language that would be appropriate for a college-educated, non-scientific person, clearly state the objectives of the research and how these experiments will help achieve these goals". (It is assumed that these persons will be reasonably familiar with basic concepts such as DNA, gene, and transgenic.) At the same time, however, this section must explain the research goals in sufficient detail to allow the specialist members of the committee to assess the experiments that are described in a later section.

We’ve been through two drafts that were rejected as being too technical and one that was rejected as being too unspecific. I’m at a loss to see how to simplify it further and maintain the level of detail that the Committee requires, but we need to get this sucker finished toot sweet because 1) it’s holding up our experiments and 2) I’m going to go nuts.

So my request to any passing non-science Dopers: please read the summary below, and tell me 1) whether it clearly conveys the reasons we are doing these studies and how animal research is involved, and if not, 2) which bits are unintelligible or confusing, or 3) any general comments you may have.

Your assistance will be most deeply and heartfeltly appreciated!

Epigenetic regulation of the genome refers to changes in gene expression due to reversible chemical modifications of DNA or DNA-regulating proteins called histones, or to silencing of genes by small RNAs. Methylation of DNA is an epigenetic modification which is important in the regulation of gene expression and chromosomal instability, and has been found to be dysregulated in many forms of cancer. This modification is placed on the DNA by a class of proteins called DNA methyltransferases; both humans and mice have three such genes (Dnmt1, Dnmt3a, Dnmt3b), each of which catalyzes methylation at defined sites in the genome.

We have developed a new transgenic “RNA interference” method which uses small RNAs to reduce the expression of the targeted gene in specific tissues, and we will use this approach to control the expression of selected genes known to participate in epigenetic regulation, including Dnmt3a and Dnmt3b.

The first aim in our study is to examine the role of epigenetic mechanisms as modifiers of tumor initiation and progression. Many types of tumors show dysregulation of DNA methylation, and abnormal DNA methylation states are known to promote tumor formation and growth in animal models of cancer and in human cancers. In order to define which epigenetic regulatory genes are important in establishing and propagating these aberrant DNA methylation states, we will breed together mutant mouse strains that are predisposed to the brain tumor medulloblastoma with transgenic mice that allow us to control the expression of epigenetic regulatory genes, and examine tumor formation in the offspring.

The second aim is to examine the effects of DNA-methylation-regulated gene expression in embryonic development. We have mouse strains with mutations in Dnmt1, and will create mouse strains with mutations in Dnmt3a and 3b, which together will allow us to eliminate DNA methylation, and thus remove DNA-methylation-dependent gene regulation. To study the effects of DNA methylation on gene regulation and development, we will breed animals with no expression or reduced expression of the various methyltransferases, and examine embryonic development and gene expression in embryos and in cell culture.

2

The Word 2002 readability puts it at:

Passive sentences - 30%
Flesch Reading Index - 15.8
Flesh-Kincaid Grade Level - 12.0

The Gunning Fox Index I ran from this web site reports:

Indication of the number of years of formal education that a person requires in order to easily understand the text on the first reading
Gunning Fog index : 23.44

Approximate representation of the U.S. grade level needed to comprehend the text :
Coleman Liau index : 14.93
Flesh Kincaid Grade level : 19.94
ARI (Automated Readability Index) : 21.14
SMOG : 19.43
In others words, it appears to me your explanation is above “a college-educated, non-scientific person.” I would venture to think someone with an advanced degree in the field.

3

By silencing genes, do you mean “turning them off”? Is this the same as dysregulating them? And this is done by the methyltransferases?

Is medulloblastoma the name/type of the tumor?

Depending on how your header and cover sheet look like, you’ve still got about a dozen lines left on a page you can use to clarify these concepts, as they seem to be a bulk of the later content.

If possible, I would reorder the wording in each of the first two sentences. My first reaction was “Epigenetic? What the hell is that?”. Although it goes on to give the definition, I felt myself having to scan back and forth after I realized you give the definition immediately following. I would prefer to either see the words you’re going to define in bold (at first appearance) or rewriting it as: "changes in gene expression due to reversible chemical modifications of DNA or DNA-regulating proteins called histones, or to silencing of genes by small RNAs is called epigenetic regulation.

FWIW, I thought the second and third paragraphs were quite clear, while I struggled with the first one. The fourth was a bit more difficult because I had to remind myself what methyltransferases were. The first was the hardest, but I think that can be easily fixed by easing into the “big words”, or words that a layperson won’t recognize.

ETA:

I think thorough understanding and “getting it” are two different things. I don’t understand what’s happening, but I “get it” enough to know what the project is doing, and be able to decide if live animals are necessary to the project if I were on the committee.

EETA: In engineering, we always say “a college educated technical person”, not a “non-scientific” one.

4

Well I’m a scientific guy, but certainly not a biology guy, and my first instinct is that the description contains approximately eleven billion times more information than is necessary to convey the desired information.

According to your instructions, there are two goals for the description: state the objectives of the research, and how these experiments will help achieve those goals.

So I would remove all the introductory stuff that explains the fancy jargon, and go with something much shorter and to-the-point. To wit:

Note that it’s mostly the same as your last two paragraphs, but I simply replaced a lot of the specific details with much more vague terms. For example, there’s no need to include the specific names of the genes, so I just say “certain genes.” There’s also no need to include the specific type of tumor, just that it’s a tumor. And so on. I thought about eliminating the phrase “DNA-methylation” as well (since it appears frequently) but I don’t know what vague term to replace it with.

I also don’t really know what “transgenic” means, exactly.

5

Are these knock-out mice?

The first paragraph seems a bit hard to understand. I think a lay reader may tune out the rest of the explanation because of that.

The first goal is also hard:
I think in the first part you are targeting some gene’s-Dnmt3a, &b with a new method that interferes with Methylation in order to determine their effects in tumor growth. You will be using mice which are both susceptible to tumors and which you have interfered with their Methylation.

The second part is looking at what happens in embryo development with no or little methylation.

I have never read a protocol but if it’s any consolation my wife has to write a couple of these a year on mice and bitches about each of them.

6

College-educated person, major English. Not a scientist. Only part I had a problem with was the word “epigenetic.” Unfortunately, that word starts off the whole thing. . .and appears lots of times. . .I got it from context, but it was a bitch.

7

First, ‘dysregulated’ doesn’t exist for most people. It isn’t a word to them. Just say ‘impaired’. Second, you’re obviously having to cram a lot of information into a few paragraphs. Decompressing a bit would help immensely.

You might just focus on how methylation of DNA is a reversible process that controlls both how a gene gets used and how likely it is to mutate, and that it is impaired in many forms of cancer. (Am I right here? Correct me if I’m wrong, but don’t just add detail for the sake of it.)

The focus here is on what methyltransferases do, and the fact mice and humans have the same specific genes relevant to their action. So stick to that. Summarize and you’re fine.

OK, this is the cool part. This actually looks pretty good in isolation. It needs to be followed by a ‘punchline’: “Why does this matter?”

So you’re giving cute little white mice brain cancer by mixing their genes with abnormal DNA. Those fools at the institute all laughed at you, didn’t they? :wink:

Seriously, this is your strong suit. Emphasize this will lead to improved genetic testing and early-warning mechanisms once we know which genes are important here. I think the main problem is that it just goes on too long.

The same thing but with a slightly different focus. Again, trim just a bit here, and make sure they don’t lose sight of the ultimate goal ([del]freaky-looking mice[/del] improved knowledge of brain cancer).

8

Give an example of “Epigenetic regulation”.

9

Thanks everyone who has responded so far!

Santo Rugger, part of the problem is that biology tends to make new jargon by taking an ordinary English word and giving it a technical meaning, so that the terms a nonspecialist might naturally use to describe a process may be entirely incompatible with the meaning those terms have in the field. “Silencing” isn’t necessarily “turning off” (the gene could be active, but prevented from making a product). Dysregulation can mean either more or less gene expression than normal. Medulloblastoma is indeed the type of tumor. “Non-scientific” is how it’s put in the instructions, not my choice of term.

friedo, your version looks a lot like our first submission, which was rejected as being “not sufficiently specific”. So we added more detail, and it came back as “too technical”. This is why I’m going grey at 34. “Transgenic” basically means “genetically engineered”, but we try to avoid the latter term since it has negative associations in the lay mind.

bannerrefugee, I think you got the gist. :slight_smile: Some of the mice we are using are indeed knock-outs (where you make a gene nonfunctional by deleting a chunk of it), some are just transgenics (which covers all genetic modifications).

Derlerth, the Committee wants detail and specifics, but also simplicity, which is what’s driving me nuts. “Dysregulation” could mean either up or down, so “impaired” may not be the right replacement; I think “abnormal regulation” might work. Unlike a grant proposal the Animal Protocol does not require explanation of how the findings will ultimately benefit mankind (and in fact we were told to lay off that kinda stuff), just explanation of what we’re planning to do and why we need to use animals to do it. And we got freaky-looking mice by the bucketful (they’re chimeras, so they start off with funky black-and-white stripes, then they get these weird domed skulls when the tumor starts to grow). :smiley:

ouryL, the classic example is tortoiseshell and calico cats, where a (usually female) cat has one X chromosome with a gene that gives them an orange coat and one with a gene for black coat; since a normal female cell only uses one of its two X chromosomes (the other is epigenetically silenced), the cat comes out with black and orange splotches.

Improved (I hope) lay abstract:
“Epigenetic regulation” of the genome refers to changes in gene expression that are due to long-lasting but reversible processes: chemical modifications of DNA or DNA-regulating proteins called histones, and suppression of gene function by small RNAs. “DNA methylation” is an epigenetic modification which is important in the regulation of gene expression and chromosome stability, and which has been found to be abnormally regulated in many forms of cancer. This modification is performed by a class of proteins called DNA methyltransferases; both humans and mice have three such genes (Dnmt1, Dnmt3a, Dnmt3b), each of which catalyzes methylation at defined sites in the genome.

We have developed a new transgenic method to control gene expression in specific tissues using an improved form of “RNA interference”, in which small RNAs reduce the expression of a target gene. We will use this approach to control the expression of epigenetic regulatory genes, including Dnmt3a and Dnmt3b.

The first aim in our study is to examine the role of epigenetic mechanisms as modifiers of tumor initiation and progression. Many types of tumors show abnormal regulation of DNA methylation, and this is known to promote tumor formation and growth in animal models of cancer and in human cancers. In order to define which epigenetic regulatory genes are important in establishing and propagating these abnormal DNA methylation states, we will breed together mutant mouse strains that are predisposed to a type of brain tumor (medulloblastoma) with transgenic mice that allow us to control the expression of epigenetic regulatory genes, and examine tumor formation in the offspring.

The second aim is to examine the effects of DNA-methylation-regulated gene expression in embryonic development. We have mouse strains with mutations in Dnmt1, and will create mouse strains with mutations in Dnmt3a and 3b. Together these mutations will allow us to eliminate DNA methylation in the mice and thus remove DNA-methylation-dependent gene regulation. To study the effects of DNA methylation on gene regulation and development, we will breed animals with reduced expression or no expression of the various methyltransferases, and examine embryonic development and gene expression in embryos and in cell culture.

10

Epigenetic I have no idea what this word means regulation of the genome refers to changes in gene expression I have no idea what “gene expression” is due to reversible chemical modifications of DNA or DNA-regulating proteins called histones, or to silencing what does “silencing” mean? of genes by small RNAswhat does an RNA do, and what’s the difference between a big one and a small one?. Methylation don’t know this word of DNA is an epigenetic modification see above which is important in the regulation of gene expression see above and chromosomal instability, and has been found to be dysregulated would be guessing what “dysregulated” (and why isn’t it “disregulated”?) means in many forms of cancer. This modification is placed on the DNA by a class of proteins called DNA methyltransferases; both humans and mice have three such genesproteins or genes? or are they the same thing? (Dnmt1, Dnmt3a, Dnmt3b), each of which catalyzes methylation at defined sites in the genome. At this point my eyes glazed over and I could get no further.

twicks, a college graduate with a PhD in the social sciences who reads a fair amount in (popular) natural history but has no frigging idea what you’re talking about.

11

If Twicks is having a hard time with it, you’re sunk, dude! :wink:

Can you post the “not specific enough” example? That would help us figure out how non-specific is TOO non-specific.

12

I talked with my wife about this thread at dinner. She says her new vet asks them to write animal protocols at a 9th grade level, the previous one asked for 3rd. Naturally each institution is different, but her initial response was that you gave way too much info. To me it reads a bit too much like an abstract.

But I guess you do what they ask you to.

She turned in an amendment to hers 7 weeks ago, to be reviewed today. That sorry office left her amendment out of their reviews.

I just made her read your new one, she says her vets would have asked for three or four sentences for the same project.

13

Ok, my shot, and as I basocally have no idea what you’re talking about, I will tell you what I think you’re saying. Maybe, if you correct mine, you will have something more dummer. :stuck_out_tongue:

Yours:

Ok here is what I got out of this. BTW I have a bachelor’s of political science, and am completely inept in biology and chemistry.

14

But the thing is, for a lay audience, the differences that you know are important within your field may not be important to them outside your field. YOU know that “silencing” does not mean “turning off,” because the gene may be active but prevented from making a product (whatever the hell that means), but from the lay person’s POV, who cares? Isn’t “turned off” correct for the concept you’re trying to convey to the lay audience? Overly-broad and if you squint at it hard inaccurate to you, but good enough for them.

There is a difference between “oversimplifying” things for the lay audience (GENES GOOD! EXCEPT WHEN GENES BAD!) and “oversimplying” things withing your field. It may inexcusable to not reflect the nuances of jargon to your peers, but these aren’t your peers.

15

Boyo Jim has hit the nail on the head with his translation, I think.

I’ve been at University (studying Business and Law) and most of your first draft appeared to have been written in Swahili for all the sense it made to me as a non-scientist. There are a lot of un-necessary specialist terms and the word “dense” springs to mind (in the sense there’s a lot to wade through, not in reference to the intelligence of the writer).

The translation Boyo Jim has provided is much clearer, easier to read, and makes perfect sense to me.

16

Only if it’s right. :wink:

17

I actually have a degree in biology, so I am not your target audience, but I have watched CFOs present scientific techniques and results to prospective investors. I also write technical documents.

First, provide definitions separate from the text for ALL technical terms.

  1. This may identify technical terms that can be replaced with general terms.
  2. Providing definitions for even the most common technical terms (enzyme) will make less common ones (methylation) more … approachable to the non-scientist.

ALWAYS use the same terms for the same thing; you refer to tumor initiation, establishment, formation, progression, propagation, and growth. Is this level of distinction accurate? If so, is it really necessary for a non-technical audience?

NO COMPOUND SENTENCES. Search on ‘and’; anywhere it is joining two clauses, separate them into two sentences. Your second paragraph is a perfect example of where you should have use separate sentences.

Don’t use “methylation” and “dysregulation” throughout the text; try something like " … a modification (specifically “methylation”; see definitions below) …", and then refer to “the modification” after that.
[Words with “y” in the middle make non-scientists nervous; their reaction is something like " Y in middle of word, chemistry term, don’t understand, brain shut-down, whoop-whoop, suspicion".
I base this on the behavior of very intelligent and well educated people whom I respect and love dearly.]

And you might consider starting with the goals of the study, describe the theory, and then sneak in the part where you play Frankenstein with and then murder the little mice.

Because people who have Orkin on retainer will still question your ethics.

Suggested words to define
Epigenetic
transgenic
Histone
“silencing”
gene expression
“small RNAs”
Methylation (or could you just call it ‘modification’?)
DNA, RNA, Chromosome
dysregulated (I wouldn’t use this word at all)
catalyze
regulatory genes
enzyme

18

Have you tried this format?

Please refer to definitions below, as indicated [the numbers I put in parentheses]

The purpose of the study is to:
0. (use the RNA interference method to develop transgenic mice)

  1. Examine the effect of reversible chemical modifications to DNA or histones (1) on tumor initiation and growth.
  2. Examine the effect of gene expression (2) regulated by DNA methylation (3) during the development of the embryo in mice.

To do so we will:

  1. Breed variant strains of mice predisposed to a specific brain tumor (medulloblastoma) with a strain of mice so as to control the expression of targeted genes.

  2. Examine tumor initiation and growth in the offspring.

  3. Develop or use existing strains of mice with no expression or reduced expression of three enzymes called 'methyl-transferases", specifically Dnmt1, […etc]

  4. Examine the development and gene expression of these strains in embryos and in cell cultures.

[this is where you put in all the stuff of epigenetic modifications, aberrant DNA states, and details of gene regulation and expression]
I see I left out the stuff about the “RNA interference method”; I just inserted it as “0.”

You should also avoid “mutant” and “create”; very Frankenstein.

19

I’ll admit it threw me and I’ve read popular biology books for fun.

I think you’re jumping in to the scientific procedures too directly. You should start by establishing the overall purpose of the program. Then describe the basic science, then define specific terms you’re using and then outline the actions you’ll be performing.

Here’s how I would have said it (assuming I understood it in the first place and acknowledging that I left out the part about embryonic development):

20

Can I hire you?

Honestly, you were clear, concise, and you managed to use three different tenses without mixing them up (I hate mixed tenses). No ‘mutants’, no ‘creation’, and even methylation seems innocuous. You have a talent.

(Combine the 2nd & 3rd sentence in the 2nd paragraph “Epigenetic regulation is one factor which …”; add the definitions and have a final draft on my desk by 10:00 …
oh, right, this isn’t my document …)