You work with WHAT?! Common misconceptions about studying nematodes

We are all worms, but I do believe I am a glow-worm”- Winston Churchill

Well, if Mr. Churchill is right, and we are all worms, I am most definitely a nematode.

Now you may be thinking, “Emily, you’ve lost it. A nematode? A toad is most definitely NOT a worm”.  Don’t worry; I haven’t totally lost it (in this instance, anyways). Nematode is another name for the roundworm, which account for over 80% of the individual animals on the planet! In our lab at the University of Washington and at labs all around the world, the nematode is very close to our hearts. This is because we study one particular species of nematode called Caenorhabditis elegans. Scientific names can often be a mouthful, so most shorten it to simply C. elegans.

When I tell people that I work on worms, I usually get a look of disgust, confusion, or skepticism.  But let’s get something straight- C. elegans are not what you are picturing. They don’t look like this:

Source: fir0002 | flagstaffotos.com.au

Source: fir0002 | flagstaffotos.com.au

Or this:

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And unfortunately, they don’t look like this either:

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In fact, C. elegans are very hard to see without a microscope. Adults are only about 1 millimeter long. To put that into perspective, a single C. elegans worm could be picked up by a single eyelash! Having a hard time picturing it? Here are a couple of views of C. elegans:

Crawling C. elegans hermaphrodite worm

Crawling C. elegans hermaphrodite worm (Photo credit: Wikipedia)

Caenorhabditis elegans

Caenorhabditis elegans (Photo credit: AJC1)

Ok, ok… but who in their right mind decided studying these tiny worms was a good idea?

Well, studying diseases in larger animals like mice and rats isn’t easy: they take a long time to develop and grow, are expensive to maintain, and are complicated in design. In the 1960’s, a scientist named Sydney Brenner suggested that studying C. elegans would improve on a lot of these problems: C. elegans only live for a few weeks in the lab, are cheap and easy to maintain, and it is easy to manipulate their genes! To put the simplicity of C. elegans into perspective, while the human body has trillions of cells, C. elegans only have around 1000 cells! Today, along with fruit flies, C. elegans is frequently used as a model organism for studying disease and cellular processes.

In the 40+ years that C. elegans have been used in scientific research, they have greatly contributed to the advancement of science, particularly in the study of aging. Many genes that make C. elegans live longer in the laboratory have been identified as important in the aging process in humans and other mammals. Additionally, C. elegans are a great model  for studying human disease, as more than half of the genes known to be involved in human disease are also found in C. elegans. For example, models of neurodegenerative diseases including Parkinson’s and Alzheimer’s have been developed, and are currently being utilized to better understand and development treatments for these diseases.

In the last 15 years, THREE Nobel Prizes have been awarded to scientists for their work in C. elegans!

Hopefully, the next time that you hear a scientist mention that they study worms, you will not necessarily picture them digging around in the dirt and looking at earthworms. While we have all been known to dig in the dirt from time to time, C. elegans researchers are tackling tough research problems from behind a microscope, using this tractable and inexpensive model organism!

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And now for some great references to find out more about C. elegans!

A Short History of C. elegans Research

Worms in SPACE?!

Wormatlas: A bit dense for the nonscientist, but great images!

Introduction to C. elegans

 

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When peer review meets the press

How do scientific ideas progress from being a project at my lab bench to being the headline story on your nightly news? The process, while all-too-familiar to research scientists, can be a bit of a black box to everyone else. In the last few weeks, this process has reached the front-page news more than once, so let’s talk about the scientific process (and some of its’ flaws)!

The first thing to realize? Science takes a very, very long time. The grant review process, the actual science, the publication process: all are notoriously slow, albeit crucial, steps in the world of science.

In order to fund, perform, and publish scientific research, scientists rely on one very important group: our peers. First, a panel of other scientists reviews our grant proposals. Once the grant is funded, collaborations are critical for the success of a research project. Finally, when the research is completed and submitted for publication, our colleagues review the manuscript for content and clarity. Involving our peers in every step of the process, in theory, ensures the funding of only the best grants and the publication of only the best scientific papers.

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Peer review can be a long, hard road for any scientist                                               (Cartoon credit: Nick D Kim, strange-matter.net)

As the title of my post suggests, the peer review process has come under scrutiny as of late. Let’s do a quick rundown of the recent headlines about the scientific process!

1) The battle over open access

If I were to give you a list of 10 influential scientific articles from the last 20 years and ask you to find full versions of them, you would have a very hard time. In fact, when you reach the website of the appropriate journal, you’d probably be asked to pay the reasonable fee of only 50-100 dollars to view the article.

Wait… $100 to read ONE article?!

The reason? Most research journals charge steep subscription fees to access their articles (current or archived). However, as a large number of these articles are from publicly funded research labs, many believe that this research should be free for anyone to read.

The good news? We have seen a rise in the number of journals with “open access” policies over the last few years. As of 2011, 12% of articles were available open access, with this number rising all the time. The availability of academic research to the public is increasing, and this is definitely a good thing!

Read more: Nature News tackles the topic of Open Access 

2) Is the peer review process in grant selection unsatisfactory?

The National Science Foundation (NSF) is a government agency that provides a large amount of funding to science and engineering research. NSF grants are selected, you guessed it, through a peer review process. After an intensive review of grants that received funding from the NSF over the last few years, some lawmakers believe that the selected grants are not always “groundbreaking” research.

To “fix” this apparent problem, Representative Lamar Smith (R-TX) drafted a bill last month to implement Congress-selected funding criteria on the grant selection process. Many scientists believe that this funding criteria, which requires grants to “answer questions or solve problems that are of utmost importance to society at large”, undermines the peer review process and would negatively impact the advancement of basic research.  Basic research, as opposed to being aimed at curing a particular disease or illness, focuses on understanding the fundamental principles of the world. While this work may not directly “advance the national health, prosperity, or welfare”, it is important an building block for our understanding of the human world. The bill, which has not been formally introduced to Congress, has sparked a large amount of debate within the scientific and political realm. How should we decide who gets funded, when the amount of funding keeps dwindling?

Read more: Science Insider on the NSF Grant Bill

3) Are timeliness and thoroughness in peer review mutually exclusive?

When something BIG happens in science, the authors want to get it out fast with as big of a splash as possible. But where do we find the balance between rushing to publish big results and allowing the peer review process to be effective?

One of those BIG things in science happened this month: Shoukhrat Mitalipov, a US researcher, reported that he had cloned human stem cells from skin cells. The research was published in the journal Cell, a prestigious journal in the scientific community. In the last few days, concerns from anonymous readers began pouring in on potential errors  in the publication. Figures were labeled incorrectly, and an image was duplicated and reused in a different section of the paper. These are the type of errors that are usually caught during the tedious peer review process. So why weren’t they corrected before the publication of such a big story?

To put it simply, this paper went through review at an incomprehensibly fast rate. To give you a framework, a case study of 2,000 manuscripts submitted to a journal in 2010 reported that the average submission took 6.8 weeks from submission to editorial decision. Mitalipov’s submission was reviewed and accepted in only 3 days. Additionally, the paper was published just 12 days after acceptance.

Cell went on to defend the speediness of their review process, stating: “It is a misrepresentation to equate slow peer review with thoroughness or rigor or to use timely peer review as a justification for sloppiness in manuscript preparation”. Thankfully, it appears that the errors in the manuscript do not impact the findings of the research. However, the negative publicity from these errors certainly detracts from the impressive and innovative science performed by Mitalipov and colleagues.

Read more: Nature News: “Human stem cells created by cloning

Read more: Nature News on Errors in Mitalipov Stem Cell Paper

Read more: 2010 Case Study on average length of peer review

Conclusions

In summary, these three stories have brought the scientific process and peer review into the spotlight. Peer review has a lot of benefits, improving the caliber of the science we deliver to the public and lowering the rate of publication of unethical scientific practices. However, the question now remains: how do we improve the peer review process to keep up with the rapid speed of scientific discovery while still yielding the high quality publications we expect?

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Some suggested reading for more information:

Nature tackles the Peer Review Debate

Nature: How are funded grants chosen?

Change the world? Challenge accepted

Graduate students are angsty. It’s true, don’t try and deny it. We are sleep-deprived and grumpy and covered in emotional bruises from being knocked down so many times. One of my friends posted this all-too-familiar sentiment to social media last week:

 “Ya know, I became a scientist because I wanted to help people. Because I wanted to cure a disease, or find a therapy, or make a discovery that changes the world. And as I sit here reading papers for class I can’t help but think there are much better ways to truly help people, and that this is all just a big joke.”

I can nearly guarantee you that every graduate student has had this thought at one point or another. We came in with such aspirations, such dreams to do something good, but as the seemingly neverending PhD continues, we start to lose our faith in this ideal. In a city like Seattle, many people our age are employed by Microsoft or Amazon, working better hours for more than twice the salary. Knowing that, it’s hard not to question our decision to go to grad school. We make very little money, see very little progress in our grueling day-to-day science, and are constantly bombarded with the premise that we are simply not as smart as everyone else. I am about to start the twentieth grade, for goodness’ sake! What am I doing here?!

177377_631228287443_2045552082_oSometimes, planning out my future feels more like drawing cartoons.

But what I’ve started to learn is this: grad school isn’t supposed to be about changing the world. It’s about changing you first.

As first years, we are as prepared to cure cancer as we are to fly a spaceship to Mars. So, we read mountains of scientific literature that we only occasionally care about (or understand, for that matter). We sit through lecture after lecture of successful scientists, sometimes understanding what they are talking about. We do an exorbitant number of experiments that fail three-quarters of the time… on a good day. But through all of that, we learn how to think. We learn how to problem solve. We learn how to be a scientist. And that’s the point of being a graduate student. At my committee meeting yesterday, my boss told me I needed to start making the transition from thinking of myself as a student to thinking of myself as a colleague. Three years ago, I would have been terrified of that transition, but after three years of grad school, I’ve changed.

Writing this blog, it’s hard to find a middle ground between the angsty overworked graduate student and the motivated inspired scientist. I’m not here to convince you that graduate school doesn’t suck. It does! But I’m also not here to convince you that it’s a worthless waste of time, because I don’t think that’s true, either. I think I am mostly trying to reaffirm that what we are doing, while not immediately changing the world, will make us the people we want to be. The people who cure cancer, who change policies, who reimagine the way science will work in 15 years.

If you were to ask my classmates, I’m sure they’d tell you that I love grad school more than most. I do. I started working in a lab at 16. I’m pretty sure my mom thought I was crazy when I walked into her room and said I wanted to give up my summer and most of my senior year to drive to Frederick and work on cancer. And, to be honest, as cliché as it all sounds, I fell in love with science that year. And until my second year of graduate school, 6 years later, I never once questioned the path I was going to take: college, research, grad school, academic researcher, rounding off my career by curing cancer.

Recently, my goals have changed a bit. I know this may come as a surprise to many, but

I probably won’t be the one to cure cancer.

I may not even be behind a microscope in 10 years (guess I’ll have to change my blog title at that point)! I do know that I love talking to people. I love engaging students who never knew that being a scientist was a possibility. I love trying to fix the Grand Canyon-sized gap between research scientists and the public. I don’t think that I would have realized these things, or been able to formulate a plan to incorporate them into a career, if I didn’t walk the long and terrifying path of graduate school.

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The realization that your scope has taught you more than it’s taught you…

As graduate students, we are, by most definitions, adults. We pay rent, we buy our own groceries, we can vote, drive cars (if we can afford the gas), pay taxes, get married, have children, buy houses. There is a quote from an early season of Grey’s Anatomy that I think describes it best:

“Four years of high school, four years of college, four years of med school. By the time we graduate we’re in our late 20s and we’ve never done anything except go to school and think about science. Time stops… And Meredith, she’s 17 years old, we’re all 17 years old”.

So, here I am, a 24-year-old graduate student, still contemplating what I want to be when I grow up. The answer currently: Who knows! That is the answer of most graduate students these days, especially with an increasing number of Ph.D.s and a diminishing resource of jobs and funding (that’s a topic for another day). But I do know that going through graduate school will be one of the biggest and best accomplishments of my life. And mark my words, I will change the world one day. I just have to work on changing myself first.

Hydrogen sulfide: A smelly, deadly gas… but could it save lives?

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Take a moment and imagine a street in Paris in the 18th century, much like this depiction of “Place du Havre, Paris, Rain” by Camille Pissarro. The first things you’ll notice: it’s beautiful, romantic, bustling. But what you might not notice is that is also very, VERY smelly.

Back then, sewer systems were extremely unsophisticated, and the smell of rotten eggs spilled into the streets. Even more, if a person were to go too far below ground, they would likely find themselves dead in minutes. The culprit? Hydrogen sulfide, a gas that smells of rotten eggs and is produced when bacteria breakdown the organic material found in sewage.

Thankfully for us, modern-day sewers have come a long way since the 18th century, but so has our understanding of this smelly, toxic gas. In the last 10-15 years, scientists have found that hydrogen sulfide is important for cell-to-cell communication in our bodies. Additionally, exposure to low levels of hydrogen sulfide has beneficial effects on many different organisms. For example, plants exposed to hydrogen sulfide grow  better, and worms grown in hydrogen sulfide are long-lived! Remarkably, in rats and mice, treatment with hydrogen sulfide also protects against damage from devastating injuries including stroke, heart attack, and severe blood loss. With so many recent discoveries highlighting the benefits of hydrogen sulfide, you may be asking yourself:

How can something that is so deadly also be beneficial?

The answer lies in the dosage. While scientists are still working on understanding HOW the gas functions in the body, we do know that hydrogen sulfide has beneficial effects at low levels, but toxic effects at high levels. The importance of dosage on human health is not just specific to smelly hydrogen sulfide. In fact, just about every substance that we come in contact with throughout the day has different effects depending on the dosage: even drinking water can be harmful if you consume too much! (Water intoxication: it’s a real thing! Read about it here.)

An easy way to think about dosage effects is the common saying (and the Kelly Clarkson pop hit):

What Doesn't Kill You, Makes You Stronger

In other words, exposure to low doses can activate cellular responses that provide protection to the cell, making it “stronger”. However, these cellular responses may be insufficient at higher doses, ultimately resulting in damage and death. 

There is a lot to learn about hydrogen sulfide before we begin using it regularly as a therapeutic. For those who work in environments where hydrogen sulfide poses a serious occupational threat, utilizing the gas for medical treatment still sounds extremely dangerous and irresponsible. By improving our understanding of the cellular effects of hydrogen sulfide at different doses, scientists can minimize potential dangers of hydrogen sulfide as a therapeutic. Ultimately, the potential benefits of hydrogen sulfide in agriculture and human health make it an important and exciting research field for the future.

If you’re interested in learning more about hydrogen sulfide, you can visit our lab’s website here!

This blog post originated as an exercise for my SciFund Challenge Outreach course, but I liked it so much that I thought it’d make a great first blog post! Let me know what you think!