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Old 06-11-2008, 03:38 PM
JR Brown JR Brown is offline
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"College-educated lay person" Dopers: Help me out!

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  
Old 06-11-2008, 04:18 PM
Duckster Duckster is offline
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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  
Old 06-11-2008, 04:20 PM
Santo Rugger Santo Rugger is offline
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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:
Quote:
Originally Posted by Duckster
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
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.

Last edited by Santo Rugger; 06-11-2008 at 04:25 PM.
  #4  
Old 06-11-2008, 04:26 PM
friedo friedo is offline
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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:

Quote:
Abnormal DNA methylation states are known to promote tumor formation growth in animal models of cancer and in human cancers. In order to define which genes are important in establishing and propagating these abnormal DNA methylation states, we will breed together mutant mouse strains that are predisposed to a particular type of tumor with transgenic mice that allow us to control the expression of certain genes, and examine tumor formation in the offspring.

Additionally, we will examine the effects of DNA-methylation-regulated gene expression in embryonic development. We can breed mouse strains with certain mutations which will allow us to eliminate DNA methylation. This allows us to 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 traits, and examine embryonic development and gene expression in embryos and in cell culture.
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  
Old 06-11-2008, 04:33 PM
bannerrefugee bannerrefugee is offline
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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  
Old 06-11-2008, 04:50 PM
Angel of the Lord Angel of the Lord is offline
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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  
Old 06-11-2008, 04:51 PM
Derleth Derleth is offline
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Quote:
Originally Posted by JR Brown
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.
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.)
Quote:
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.
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.
Quote:
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.
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?"
Quote:
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.
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?

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.
Quote:
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.
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 (freaky-looking mice improved knowledge of brain cancer).
  #8  
Old 06-11-2008, 05:42 PM
ouryL ouryL is offline
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Give an example of "Epigenetic regulation".
  #9  
Old 06-11-2008, 05:57 PM
JR Brown JR Brown is offline
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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. 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).

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  
Old 06-11-2008, 06:53 PM
twickster twickster is offline
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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  
Old 06-11-2008, 07:55 PM
freckafree freckafree is offline
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If Twicks is having a hard time with it, you're sunk, dude!

Can you post the "not specific enough" example? That would help us figure out how non-specific is TOO non-specific.
  #12  
Old 06-11-2008, 08:47 PM
bannerrefugee bannerrefugee is offline
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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.

Last edited by bannerrefugee; 06-11-2008 at 08:48 PM.
  #13  
Old 06-11-2008, 08:51 PM
Boyo Jim Boyo Jim is offline
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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.

Yours:
Quote:
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.
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.

Quote:
Epigenetic regulation of the genome refers to a method of controlling how genes function in our bodies by means of chemically changing certain proteins called histones. These changes can be reversed. One method of controlling these genetic functions is called DNA-methylation. Research has found that certain types of cancer affect the methylation process. Certain types of genes are called DNA methyltransferases because they affect how DNA-methylation works at specific places on the genome. Humans and mice share three of these genes -- Dnmt1, Dnmt3a, and Dnmt3b.

We have developed a new method which to reduce the effect of the targeted gene in specific tissues, and we will use this approach to control the effect 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 these processes on tumor initiation and progression. Many types of tumors result in changes 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 methylation states, we will breed two particular strains of laboratory mice together. One type of mouse is predisposed to the brain tumor medulloblastoma, and the other type that ___ (er, what makes the other strain of mice special?). The offspring will allow us to control the expression of epigenetic regulatory genes, and examine tumor formation in them under controlled conditions.

The second aim is to examine the role of these processes in embryonic development. We will breed mice that do not have any, or have greatly reduced, methylation-dependent gene regulation. With embryos and live mice bred in this manner, we hope to be able to compare genetic function and cellular development in two strains of mice, one with and one without, methylation-dependent gene regulation. The results should give us a much clearer picture of what changes in cell development can be attributed to this process as opposed to other possibe genetic therapeutic approaches.
  #14  
Old 06-11-2008, 08:56 PM
Jodi Jodi is offline
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Quote:
Originally Posted by JR Brown
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.
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.

Last edited by Jodi; 06-11-2008 at 08:57 PM.
  #15  
Old 06-11-2008, 08:58 PM
Martini Enfield Martini Enfield is offline
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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  
Old 06-11-2008, 09:00 PM
Boyo Jim Boyo Jim is offline
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Quote:
Originally Posted by Martini Enfield
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.
Only if it's right.
  #17  
Old 06-11-2008, 09:32 PM
j666 j666 is offline
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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  
Old 06-11-2008, 10:06 PM
j666 j666 is offline
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This is the kind of structure I'd suggest

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  
Old 06-11-2008, 10:17 PM
Little Nemo Little Nemo is offline
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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):
Quote:
The purpose of our tests will be to study how genes can affect tumors.

Gene expression is the process by which an existing gene can be triggered to produce a protein or other genetic product. There are various factors which can cause or modify gene expression. One of these is epigenetic regulation. Epigenetic regulation are changes in gene expression caused by chemical modifications of DNA. One specific type of epigenetic regulation is methylation, which is caused by a class of proteins called DNA methyltransferases. Humans and mice share three genes (Dnmt1, Dnmt3a, Dnmt3b) which are subject to methylation. The changes in genetic expression caused by methylation have been found to be present in many forms of tumors.

We have used genetic engineering to develop a new "RNA interference" method. This method introduces RNA into the gene in order to reduce its genetic expression. We will be using it on the above mentioned Dnmt3a and Dnmt3b genes in a population of mice. This will allow us to develop a population of mice that have reduced DNA methylation states.

We will then breed these mice with a population of mice that have an existing predisposition to develop a brain tumor called medulloblastoma. This resulting population mice will have reduced DNA methylation states (which promotes tumor formation and growth) and a predispostion to developing a specific tumor. By studying this population we will be able to measure the role of DNA methylation in tumor formation and growth.
  #20  
Old 06-11-2008, 10:44 PM
j666 j666 is offline
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Quote:
Originally Posted by Little Nemo
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 ...
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 ...)
  #21  
Old 06-11-2008, 11:30 PM
Mongo Ponton Mongo Ponton is offline
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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.
  #22  
Old 06-12-2008, 01:15 AM
Little Nemo Little Nemo is offline
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Quote:
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.
Thank you. Writing reports is essentially what I do for a living. Twenty five years of practice have made me fairly good at it.

Last edited by Little Nemo; 06-12-2008 at 01:15 AM.
  #23  
Old 06-12-2008, 06:53 AM
brujaja brujaja is offline
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"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--
  #24  
Old 06-12-2008, 10:10 AM
JR Brown JR Brown is offline
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Originally Posted by Jodi
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.
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.
  #25  
Old 06-12-2008, 10:29 AM
JR Brown JR Brown is offline
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Quote:
Originally Posted by Mongo Ponton
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.
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.
  #26  
Old 06-12-2008, 10:36 AM
JR Brown JR Brown is offline
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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.
  #27  
Old 06-12-2008, 07:09 PM
j666 j666 is offline
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Quote:
Originally Posted by JR Brown
... 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.
  #28  
Old 06-12-2008, 07:19 PM
Santo Rugger Santo Rugger is offline
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Quote:
Originally Posted by JR Brown
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.
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.

Sounds like fun stuff, good luck!
  #29  
Old 06-12-2008, 07:52 PM
Zsofia Zsofia is offline
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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.
  #30  
Old 06-13-2008, 02:33 PM
JR Brown JR Brown is offline
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A breakthrough has been achieved

(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 mouth-breathers 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.

Last edited by JR Brown; 06-13-2008 at 02:37 PM.
  #31  
Old 06-13-2008, 05:57 PM
twickster twickster is offline
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Yay! I understood this!
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