Rita Levi Montalcini and Nerve Growth Factor: Repost

This last week one of my neuroscience heroes, Rita Levi Montalcini, passed away at the age of 103. In her honor, I decided to repost a post I wrote a few months ago about one of her greatest contributions to science: nerve growth factor. In addition there’s a nice profile of her and her work in Nature. Here’s the repost:

A Neuroscience Field Guide: Nerve Growth Factor

Nerve growth factor, NGF for short, is a soluble protein that is secreted by various tissues in the body, and it promotes the growth of nerve cell processes and survival of neurons. It is the first of a class of molecules known as neurotrophins which are very important for the development and function of the nervous system.

What is remarkable about NGF is how it was discovered and by whom. NGF was discovered by Rita Levi-Montalcini an Italian, Jewish young doctor. She originally became interested in a set of experiments by renowned embryologist Viktor Hamburger which had observed that removing a limb bud from a chicken embryo caused the sensory neurons that innervated the undeveloped limb to die off. This suggested that there was something about the target tissue that promoted neurons’ survival in the embryo.

Levi-Montalcini had just graduated from medical school when Mussolini issued the “Manifesto per la Difesa della Razza”, which ultimately led to a ban of all non-Aryans from having professional and academic careers. Undaunted, Levi-Montalcini set up a laboratory in her bedroom in her parents house and then after the bombing of Turin in her family’s country cottage. After the War she was invited to St. Louis, MO to join Viktor Hamburger where she remained for many years and where she performed her Nobel Prize-winning research.

One of her initial observations was that if you implant specific mouse tumor cells on a chick embryo, sensory neurons will grow rapidly and sprout new axons which will innervate the tumor cells, again confirming that certain target tissues can promote nerve growth in embryonic tissues. The question was how did the target tissues do this? The key experiment came when she and her colleagues grew on one end of a cell culture dish some of these mouse tumor cells, and on the other a bit of neural tissue known as a sensory ganglion. After a few days, she observed that the neurons in the sensory ganglia grew a bunch new axons, and these axons seemed to be oriented toward the tumor cells. As if they were being attracted. This told her that the tumor cells were actually releasing some soluble factor into the growth media. The factor promoted growth of nerve cells and helped them live longer in a culture dish. This factor was later isolated by biochemist Stanley Cohen and shown to be a protein which they dubbed, imaginatively, nerve growth factor. Both Cohen and Levi-Montalcini received Nobel Prize in 1986.

 

From Levi-Montalcini’s Nobel Lecture: Drawing of the cell culture experiment. The tissue on the left is the mouse tumor cells, the tissue on the left is the sensory ganglion. Note the axons growing out towards the mouse tissue.

 

How does NGF work? Now we know that NGF, as well as several other similar proteins known as neurotrophins, activate receptors in target cells which are called tyrosine receptor kinases, or Trk. Trks are proteins which are on the surface of neurons that when activated by NGF cause a series of cellular processes which cause embryonic neurons to grow new axons and to survive. Any cells which do not find their target will undergo a self-destructive process called apoptosis, thus help in the developing nervous system keep appropriate connections and eliminate inappropriate ones. Furthermore, NGF could form the basis of new therapies for treating various degenerative brain disorders and maybe promote neural regeneration after injury.

Rita Levi-Montalcini is now 103 years old, the oldest living Nobel laureate. Apparently she uses NGF eye-drops daily (it’s true!).

Rita Levi-Montalcini in 2009, at her 100th birthday party.

 

Further Reading

Rita Levi-Montalcini Nobel Lecture and her Autobiography

Stanley Cohen Nobel Lecture

 

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STEM-migration

I was just recently reading a news piece announcing that the US House of Representatives approved a bill to allow 55,000 foreign students, who obtain a higher degree (PhD or Masters) in a STEM field in a US university, to apply for permanent residency in the US. This was apparently a bipartisan effort supported both by Democrats and Republicans. On the face of it, this is great news, it increases influx and retention of highly intelligent foreign scientists and engineers to the US. However there are a few caveats that make it less desirable. For one, this is not a trivial process, the bill requires that applicants go through labor certification, which means that you need an offer from a university who is willing to hire you and sponsor you and then they need to post the job offer to make sure that some more worthy US citizen couldn’t fill this position first. This is a long, tedious process which universities and other employers go through now to hire people under H visas. Another limitation is that the bill excludes anyone in a biomedical field. Arguably research in biology and medicine is one of the most critically important areas of current scientific focus, and it seems shortsighted to eliminate this category altogether. Finally, if this program were to pass, it would completely replace the diversity visa category, basically a green card lottery to enable folks from various underrepresented areas of the world to immigrate to the US. Since there are less PhDs graduating in the “hard” stem fields than the 55,000 slots, the net result is a decrease in immigration. So while this bill seems like a step in the right direction, I wish it had been somewhat better thought out.

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How to write a grant

Maybe the title is misleading. In this post I will not be talking about how to organize, structure and present ideas in your grant. This is not about what you put in your grant. That’s up to you. What I will be talking about is what your grant should look like. Recently I’ve been dealing with graduate students putting together two-page graduate fellowships for the NSF which are due, like, this week. This is typically the first taste of grant writing students get, and it shows. Not only are thoughts disorganized, ideas vague and descriptions wordy, but the drafts often just look like crap. I’ve gotten everything from 2 pages crammed with impenetrable walls of text, or grants that are one page over the limit or something so sparse and thin that while it fills the 2 pages, there’s about zero content. And of course I wouldn’t expect any different, since these folks have had no prior experience or guidance. One thing that is often overlooked in grant workshops is how to make your grants more readable and pleasing to the eye. Most granting agencies have strict limitations on font types and sizes you could use, as well as specific margin sizes and line spacings. But even within these constraints there are good and bad practices regarding how you format your grant.

What follows is a miniguide of practices I follow to maximize the amount of space to put information in, without sacrificing readability and pissing off all of your caffeine-addled reviewers. I won’t even go on about which font is better, people have strong feelings about what works and which doesn’t and these arguments run deep. I will just tell you how I format my grants, I’m sure you can adapt these tips to your personal font preferences:

1. First and foremost, keep in mind that grants have a page limit for a reason. If the limit is two pages, then write two pages worth of grant, not six and try to fit it all in into two. But even if you are conscientious about page limits, there’s always that extra paragraph that you want to add describing that extra method, or alternative interpretations of your results, or whatever. How do you squeeze this in?

2. Turn on hyphenation: This will not only shave off a few lines from your proposal (up to half a page for a 10 page proposal), but it will make your right margins neater. It is never a good idea to turn on right justification, because although the text looks prettier, it makes it hard to read. With hyphenation, it will tighten up the right unjustified margin without detracting from ease of reading.

3. Use several short paragraphs and don’t skimp on headings: Often I’ve seen grants with page-long single-paragraph walls of text, with headings embedded in bold lettering within the text. While this impenetrable wall might be useful for keeping out the wildlings, it is very difficult to read. So use headings to organize your proposal, write several short paragraphs containing one or two ideas, this makes it so much more readable and increases blessed white-space on the page. “But,” you say, “I can’t afford to waste all those empty lines between paragraphs and after headings?” True, these two things use up precious space, but one way in which you can minimize the use of empty line-space, yet still open up your text, is to set spacing following each paragraph to be 6 points. That way, you have a half line of space between paragraphs to make it look good, but you save a few lines.

4. Use 11 point Arial and set line spacing to be exactly 12 points: This combo will pass muster of most spacing requirements (certainly NIH and NSF), yet minimize amount of space used and remain highly readable. When you set your word processor to “single space” it usually uses 13 or 14 pts, which is necessary for 12 pt font, but with 11 pt font, 12 pt spacing is fine. Keep in mind that 11 pt Times New Roman is too small, and 11 pt Georgia will look crappy with 12pt spacing.

5. Don’t use gratuitous figures: While figures are good for presenting preliminary data and outlining experimental design, use them judiciously. Often they are not necessary and take up a bunch of space that could be used for clarifying your methodology, emphasizing your key points or what not. If you do use a figure, put it and its legend in a text-box and wrap the main text around it, leaving about 6 points of white space around it. For the legend you can get away with 9 pt Arial, maybe even 8pt if you are really tight for space.

6. Remove danglers: Often you will have in the last line of the paragraph one or two words taking up an entire line. Try to rearrange and rewrite some of the preceding text so that these dangling words are carried back into the preceding line.

That’s it!  These tips and tricks will allow you to maximize use of space yet have high-readability. And while they will save you a few lines, perhaps half a page, they will not turn a 9 page proposal into a 6 pager. For this you will have to work on eliminating unnecessary or duplicated sentences and even whole paragraphs, which is much, much harder.

Do you have any other tips and tricks you’d like to share?

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Like Mitt

You know, I don’t really feel bad for Mitt Romney. Because even thought he lost the election, he can just go back to being, well, Mitt Romney. Living the life he’s always led. I often think, why can’t we all live more like Mitt? Jet-setting and stuff. So I’ve started to think of ways in which I could acquire a lifestyle more like Mitt’s.

Fortunately, I just got invited to a “brainstorming power-lunch” about how us shlumpy scientists could form partnerships with well-dressed industry folks to make mucho dinero! This one seems specifically focused to my broad area of research, and the university has invited a couple of local industry folks working in our area as well as some venture capitalists. I can understand why the uni is keen on holding such meetings, because universities can’t function on indirect costs, tuition and fundraising alone, and their intellectual capital is supposedly highly marketable.

So should I start picking out my new jet and livin’ la vida loca? I don’t think so. I may be naive here, but I just don’t see it. I don’t see how any of my research make any money for anyone. Yea, I know some folks who have started companies and filed patents, and maybe some of those folks have made some extra cash from these enterprises, and yes, maybe an even smaller subset has made a not-so-insubstantial amount of money. But still, our research is so basic and far from anything immediately clinical, that I just don’t see it. And it’s not that I’m against this sort of stuff, the purity of science and what not. No, I would love to cash in on all our hard work, and the only way basic research can become truly translational is through such partnerships. Unless the government gets into the drug-development business. But with my research I just don’t see it. Who knows, maybe these folks will illuminate me, and at the least I get a free lunch.

How about you, readers, do you often think about how you could monetize your research? Have you tried? If so have you been successful?

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Calaveras 3.0

In México, November 2 is Día de Muertos or Day of the Dead. One venerable tradition is to write little obituaries for living people you know with a little skeleton of themselves, or a sugar skull with their name to accompany it. Newspapers will write funny obituaries, usually in verse of politicians and other public figures. These fake obits are known as “Calaveras”. For the last couple of years, I’ve written some calaveras of a few fellow science bloggers. To continue the tradition I’m happy to present a new set of calavers of some fellow bloggers I’ve had the pleasure to interact with in the previous year. Enjoy!

Pobrecita SciCurious, killed by curiosity.

No matter how much she would try,

Death could not evade poor old Sci.

We tried to save her from the monster brain,

that chased her, again and again.

But one day as she was writing el blog,

monster brain caught her, as she tripped over a stupid log!

 

Prof-like Substance, R.I.P.

Prof-like substance was always confusing.

What sort of substance makes a professor?

He wrote this blog, about how academia was a slog,

until he died by falling into his substantial processor.

¿Qué?

PalMD, fightin’ hacks and quacks!

Dr. Pal has finally gone underground.

Not in a white coat but under a mound.

He was fighting off quacks, chiropractors and hacks.

When a homeopath fired a round of projectiles.

Although the bullets were diluted a million times over,

poor  Pal was still felled by placebo effectiles.

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Dudes! Students need your help!

OK folks, I’ve dropped the ball!! With all this SfN + grantwriting craziness going on in recent weeks I just realized that our annual Donor’s Choose campaign is going on. That’s when science bloggers put up little giving pages to raise money for schoolkids in need via the charity called Donor’s Choose. You (the reader) basically browse through the various requests from teachers to fund projects and you give money to them. If enough dough is raised, the classroom get’s a new microscope, or computer, or science experiment or carpet. Yes, some don’t have carpets for the kids to gather. In any case rather than me set up another giving page in the few days that are left, I’m going to urge you to go visit the giving pages of fellow Scientopia bloggers and give there, so we have hopes of completing some projects. For example DrugMonkey is raising money for genotyping kits for an AP bio class. Or GertyZ is raising money so a class can do a chicken hatching exercise. Prof-like Substance is raising money for a microscope! And Christina Lis is raising money for circuit boards. So go to these pages and others and fund some projects! I know I am.

 

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John Lennon

I remember in 1980, when I was nine or so, hearing on the car radio that John Lennon had been shot. My older brother started acting all upset, and I figured I should too. He then looked at me and said,

“I bet you don’t even know who John Lennon is!”

“Sure I do.”

“OK, who?”

“He’s the lead singer from KISS!”

 

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Breakfast

Must kids always fill up every possible second of free auditory space, bickering, asking, yelling, singing, repeating the same fucking phrase over and over again, calling the dog, demanding, to the point that it becomes impossible to formulate a coherent thought and you pour olive oil into a glass of milk, hot sauce in your coffee and you burn the toast?

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Potions 101: Blueberry Shrub

Somehow we never get around to going blueberry picking until some point in September when late-season  varieties are ripe, and when we do, between the kids, supercoolwife and I we end up with pounds and pounds of blueberries. Which means blueberries for breakfast, lunch and dinner, as well as various pies, muffins and buckles. And even then we still end up with way more than we can consume. Thus it becomes time to pull out the cider vinegar and make one of my favorite drink-additives: blueberry shrub.

A shrub is a sweet, flavored vinegar which you add to water or seltzer to make a refreshing drink. This was a typical drink in the 1900’s. Or so they say. You can make it with any fruit (raspberry shrub is delicious) and blueberries are specially amenable to “shrubbing”. So here’s a delicious recipe to try with your extra blueberries, raspberries, strawberries, pears  and what not:

Take about a quart of blueberries and rinse them well, removing any overly mushy ones. Put them into a glass pitcher or ceramic bowl and pour over enough apple cider vinegar to cover the fruit. The better the vinegar, the better the drink, but any ol’ cider vinegar will work great. Mush up the fruit with a wooden spoon and cover tightly. Let it sit for 3-7 days on the counter, stirring it around once a day or so.

Macerating the fruit.

Pour the fruit mix onto a small saucepan, and add 1/2-1 cup of sugar and bring to a boil. Simmer gently for about 15 minutes and open all your windows because it’ll make a big vinegary stink.Take the boiled mix and filter it through a fine colander onto a bowl or small pitcher. Pour into sealable jars, bottle or whatever’s around. This will keep in the fridge for 2-3 months (though you’ll likely drink it before then).

Stinkin’ up the place.

To make a drink, take a tall glass and fill it with ice and bubbly seltzer. Then add 1-3 tablespoons of shrub (to taste) and stir. Now drink it!

I’ll leave it to my friend Doc Becca to come up with a blueberry shrub based cocktail.

 

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Thank a nurse and give blood!

As some of you may remember, almost 2 years ago I got pretty sick. Thankfully I’m doing somewhat better now and am in the middle of a two-year long maintenance treatment. I’m currently writing this as I receive medicine through a port implanted in my chest by my shoulder and I’ve been here all day, I still have another 150 ml to go. I decided that rather than watch another episode of Breaking Bad on Netflix, I should write a little blog post. The clinic is essentially run by nurses who have received specialized training in oncology and totally kick-ass at their jobs. One thing I was thinking about just now  is that several of the nurses in this room have literally saved my life multiple times, they have given me drugs to treat my disease, and when the going was rough given me life-saving blood transfusions and other medication. And I see them running around the room saving other people’s lives too, all day long. How many people can say that they directly saved several lives today? I certainly can’t. Probably most of you can’t either. You might say, “wait a minute you and we are performing basic biomedical research that will unlock key insights that can one day save peoples lives”. And I know basic research is necessary, without it none of the treatments I’ve received would have been possible, and having a basic science background certainly has helped in understanding various options. But still, my job seems completely trite and meaningless compared with the direct impact that these nurses have on their patients. And I really admire them for this.

So, if you ever meet a nurse, thank them on my behalf, if you are one reading this, thank you. Oh, and please go donate blood, this will certainly help someone directly, and thank you for doing so! Maybe we should start a little campaign to get science bloggers and their readers to donate blood, if you do donate send me a note, and I’ll publish the tally a month from now. See if we can get a modest 15 people to donate blood and thank a nurse, here we go!

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