What am I researching in the lab?

As a PhD student working in a lab, I am studying "microRNA function during aging in Caenorhabditis elegans". But what does any of that mean?? Let's break it down:

microRNA = 

-type of gene that is found in humans and also found in many other animals we study in the lab, as well as plants

-these genes are non-coding RNAs because they do not follow the "central dogma" of molecular biology, which is that DNA makes RNA makes protein. Instead, these genes make RNA, but then the RNA never codes for a protein. Instead, this RNA, which is short in length and why it is specifically called microRNA, binds to other coding RNAs and causes degradation of these RNAs and/or prevents these RNAs from coding protein. 

-as molecular biologists have thought for a long time that RNA is only an "intermediary" and has no functional role, the discovery of these microRNAs with a regulatory function was very exciting and opened up a whole new field of research. Humans have over 1000 microRNAs, so there is a lot to study regarding in which cells/tissues the microRNAs are expressed and which coding RNAs they target!

aging = 

-the biological process for how living things "get old"

-many different types of genes are involved in controlling aging, including microRNAs, which shows that aging is a programmed process and not just a random occurrence

-I am interested in studying microRNAs and aging to learn how we can promote healthy aging by preserving youthful genetic features

Caenorhabditis elegans = C. elegans = 

-the model organism I am using to study the process of aging, as it is much too difficult to study human aging because we live for so many years!

-C. elegans is a simple animal, called a nematode or roundworm. It only lives for 2-3 weeks, which makes it very easy to study aging of C. elegans in the lab and conduct many experiments

-C. elegans also has microRNAs (~150), many of which have homologous sequences to human microRNAs, so I am interested in studying how these microRNAs affect C. elegans aging: in which tissues and when are the microRNAs expressed? what happens to the worm's lifespan when you get rid of the microRNA? 

So, I can learn about how C. elegans microRNAs affect its aging processes and extrapolate how the microRNAs may work in humans! To conduct actual human studies, scientists have set up longitudinal aging studies to follow study participants over many years; a small blood sample that you would provide at a routine doctor's visit could also be used to look at the function of all of your genes at the time the blood sample was taken using various lab technologies. 

The dilemma of federal funding for science research

Recently I attended Capitol Hill Day, which is organized twice a year by the Coalition for the Life Sciences, an alliance of several organizations focused on science policy. I encourage all scientists (grad students, postdocs, professors) to participate in this event! During Capitol Hill Day, our group of scientists met with staff members of various senators and representatives to discuss the importance of long-term, sustainable federal funding of biomedical research. The National Institutes of Health (NIH) and the National Science Foundation (NSF) are primarily responsible for funding research at universities, but there is a threat that this funding will be reduced significantly in the next fiscal year. In a dire economy, it is difficult to make decisions about what takes precedence in terms of receiving funding from the government; however, we scientists urged Congress to understand that the situation is already very bad, and we fear that if funds are cut even further, this will result in a complete standstill of science research across the country.

The NIH and NSF fund grants for science research at institutions nationwide; without these grants, it would be impossible for a laboratory group to continue to conduct research. New professors are especially desperate for these grants; the lack of funding is part of the reason why it has been shown that only a meager 5% of science PhDs end up becoming tenured professors. In this new age of technological advancements, there are many new sophisticated techniques that scientists can use to conduct their research in a thorough and comprehensive manner; however, these technologies can be very expensive, and most laboratories will require multiple federal grants to cover the costs. We should not deny scientists the opportunity to conduct the best research possible, as the biomedical discoveries being made in labs across the country directly affect the well-being of us all, now and in the future. For example, I am studying the genetics of aging, i.e. factors - separate from your surrounding environment - that are already "encoded" within you that determine how long you may live. As the American population continues to live longer, it is becoming increasingly critical to understand the process of how aging actually occurs, so that we can work towards developing therapies for promoting healthy aging in all individuals.

I will admit that some scientists are better than others in terms of explaining to the general public the importance and relevance of their research, which I feel is a real misfortune because the research of biomedical scientists is directly related to improving the quality of life of the general public! This disconnect could be responsible for the stereotype of scientists as elitist or unapproachable (which is of course not true), and improving communication between scientists and the general public (and especially those responsible for funding research) could alleviate any confusion and increase awareness regarding the importance of our research.

Besides funding new or continued research grant proposals, the NIH and NSF also provide funding to institutions for training grants for PhD students. I was surprised to learn that most of the people I met with on Capitol Hill did not realize that training new science PhDs is one of the critical uses of federal funding! I have witnessed a generation of young, intelligent individuals committed to conducting science research and helping our country be a leader in biomedical discoveries; we have received federal support along this journey, of which we are extremely thankful. However, the problem we now face is that our government needs to follow up on its investments - all of these new PhDs who wish to continue conducting research and start their own labs cannot do so because of the lack of funding for new research grants. I personally feel that all this potential in current and future generations of scientists is quickly fading away.

Another example of how federal funding is used is developing science education outreach programs. Scientists including myself have volunteered with an outreach program called Family Science Nights, which is an after-school program where scientists set up demo lab experiments that elementary and middle school students can do; parents are also encouraged to work with their children to do the demos, as well. These programs promote scientific curiosity, learning how to apply the scientific method, and doing hands-on experiments to get both students and parents interested and excited about science. The Family Science Nights also encourage students to design their own science fair project by the end of the school year and participate in the city-wide Science Fair. These science outreach programs are critical because we as lab scientists have access to materials and equipment that are simply not available in the average public school because they are too costly. Additionally, the volunteers can be mentors and role models for the students, acting as real-life examples of what you could become if you study and enjoy doing science. I believe there should be many more relationships developing between public schools and university scientists across the country. Nationwide, students are performing very poorly in science compared to other subjects. According to the College Readiness Benchmarks set by the standard-test makers, ACT, only 30% of high school graduates met the "benchmark" of being likely to pass a first-year college course in science without remedial classwork. It is clear that we need to act now to improve science education, starting with younger children and continuing through high school.

Lastly, I will mention that without these grants from the NIH and NSF, we will not only lose future generations of science PhDs, witness many university labs shutting down and ceasing research, and dissolve any outreach programs in the schools, but the future of that city's local economy will also be disrupted on a large scale. Every science lab indirectly employs many other workers, including marketing, production and distribution of all the products and equipment we use in the lab, other start-up companies founded on research done in the lab, etc. Scientists do, in fact, have a large contribution to the economy.

      Overall, I had a very positive impression of my meetings with the congressmen's staff; we engaged in fruitful discussions about where scientists stand regarding the importance of federal funding of science research, and where the government stands regarding how to allocate said funding. It seems that there are still many decisions left to be made before the budget for the next fiscal year is complete, so I remain cautiously optimistic that funding for biomedical research will be maintained at the highest level possible.

During the Capitol Hill Day that I attended, there were about 20 graduate students, postdocs and professors representing states from all over the country; I enjoyed meeting all these scientists with a similar interest in advocating for sustainable federal funding for biomedical research. We all had our own personal stories to explain to the congressmen's staff exactly how this funding is so critical for the work we do on a daily basis, as well as how our research directly impacts the economy. There was also a staff member from the Coalition for the Life Sciences present at all of these meetings to help us get our points across. For example, one of the main goals for this Capitol Hill Day was to ask Congress to protect the NIH and NSF from sequestration, which will go into effect January 1 unless a vote is made beforehand. This would result in a 22% cut for the NIH and 29% cut for the NSF over 9 years, which would have an unrecoverable effect on each of our labs in particular and on the biomedical enterprise as a whole. Additionally, we stressed to Congress that the increase in federal funding for biomedical research has not been above inflation since 2003, so we have already witnessed the impacts of constricted funding. We had the opportunity to meet with congressmen's staff from our state as well as from a few neighboring states; although there was limited time to get our points across, I really enjoyed my discussions with the staff members, who all seemed to be very receptive to our cause and interested to hear our personal accounts. It was very clear to me, though, that without the Coalition for the Life Sciences organizing and facilitating all of these meetings, it would have been extremely difficult for me to actually have these discussions.

Scientists today need to include advocacy as part of their job description; we all need to spend more time being involved with programs like Capitol Hill Day or being grassroot advocates for the Coalition for the Life Sciences, where we can make our voices heard and ensure that the funding for our research will still be here for years to come. During Capitol Hill Day, I had the pleasure of listening to a briefing by Dr. Siddartha Mukherjee, who presented a historical perspective of how cancer research has changed over the years, which is also described in his book, "Emperor of All Maladies". At the conclusion of his talk, Dr. Mukherjee stressed to the audience the importance of funding for research to help address issues like the costs of personalized therapies, developing better clinical trials, and training young scientists. He made it clear that all of the research he was describing, as well as any future prospects of continued biomedical research, would not have been possible without scientists advocating for NIH and NSF funding. Following in Dr. Mukherjee's footsteps, I have invited one of the senators from my state to come visit our university's laboratories and see the research we are conducting; I hope this can be an example of how to solidify a relationship between scientists and Congress now and in the future.

Worms in space: Spaceflight slows aging of the model organism C. elegans

I study genetics of aging in the nematode worm Caenorhabditis elegans. C. elegans is a simple animal model organism that has been studied in the lab for a few decades. The adult roundworm is about 1mm long and consists of about 1000 cells. Conveniently, the fate of every cell division from fertilization until the worm reaches adulthood (which takes about 3 days) has been mapped out by scientists, so that we know exactly how every cell division occurs in order for the worm to develop into an organism of multiple tissues and specialized cell types. Additionally, scientists have also sequenced the entire C. elegans genome, so we can study any gene with any particular function of interest. These two key features, along with many other lab techniques that have been well-established when studying worms, make C. elegans an attractive animal model system. Scientists may utilize C. elegans to study neurobiology, development, stem cell biology, etc. I utilize C. elegans as a model for studying aging because many genes important for regulating aging process (such as genes in hormonal pathways, genes involved in nutrient uptake, and genes expressed in the mitochondria) are conserved from C. elegans to humans. Additionally, C. elegans adult worms only live for 2-3 weeks, so I can easily conduct multiple experiments over the entire lifespan of a worm in a short amount of time.
              While perusing through recent scientific articles about C. elegans aging, I came across an article by Yoko Honda and colleagues, entitled “Genes down-regulated in spaceflight are involved in the control of longevity in Caenorhabditis elegans” (Scientific Reports 2: 487, 2012). Here is the article link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390002/pdf/srep00487.pdf. The title immediately caught my attention, not just because I am interested in genes that regulate longevity in C. elegans, but mostly because these scientists studied longevity of C. elegans in space! Their research is literally out of this world! (Sorry for the cheesy pun.)  Oftentimes a space exploration will also carry some lab specimens along for the ride, so that we can learn more about how spaceflight impacts living things. Honda and colleagues claim that studying the impact of spaceflight on C. elegans aging is important because soon humans will be spending more time in space as we explore other planets or colonize the moon. These statements are a bit far-fetched because our daily lives will not resemble an episode of “Futurama” any time soon; however, we can argue that studying the effect of spaceflight on aging is intriguing from a physics standpoint; remember learning about Albert Einstein’s theory that if you travel into space and come back to Earth, you will be much younger than you were supposed to be? This is part of the theory of relativity: the faster you travel through space, the slower you will travel through time.

             By using C. elegans as a model system, Honda and colleagues have shown that this is actually true – worms do slow down the natural process of aging when they are in space! The researchers were able to make this claim based on a few findings from their research. They utilized data from the International C. elegans Experiment First Project, in which they compared data from “space-flown” vs. “ground control worms” over a 16-day period, where the worms were either on ground for 16 days or were or ground for 5 days and then space-flown for 11 days.

In the first experiment, the scientists looked at the accumulation of protein aggregates consisting of 35-glutamine repeats. It was previously shown that these aggregates accumulate with increasing age in the worm; in fact, these are the same type of aggregates that accumulate in the brain of patients with polyglutamine diseases like Huntington’s Disease. The researchers tagged these aggregates with a fluorescent protein in order to easily count the number of aggregates under the microscope by looking at the amount of fluorescence. They saw that spaceflight reduced the accumulation of these polyglutamine aggregates, in which worms of the same age that were space-flown had fewer aggregates than worms that were not space-flown. As accumulation of these aggregates is a biomarker for aging, this means that the space-flown worms were aging more slowly!

           The second experiment which showed that spaceflight slows down worm aging was conducted by using a DNA microarray, which is a technique to measure changes in gene expression between two different conditions. (This is where the sequenced genome of C. elegans comes in handy because the DNA microarray allows you to look at many, many genes at once.) For this experiment, scientists compared gene expression between space-flown vs. ground control worms. There were many genes that were either up- or down-regulated compared between the two different environmental conditions. However, Honda and colleagues analyzed this data and noticed that seven genes important for neuronal and endocrine signaling were down-regulated in the space-flown worms compared to the ground control worms. By applying certain lab techniques to worms that were not space-flown, the researchers saw that inactivation of these same seven genes resulted in increased longevity of the worms. Therefore, when these genes are not functioning, the worms live longer, which means that these genes antagonize longevity. Since the space-flown worms had much lower expression levels of these genes, this indicates that the space-flown worms were aging more slowly than their ground control counterparts. The researchers went on to demonstrate that, for three of these seven genes, there is less accumulation of polyglutamine aggregates when the genes are inactivated, further indicating that these genes antagonize longevity when functioning normally.

Honda and colleagues concluded from these experiments that C. elegans worms age more slowly due to a neuronal and endocrine response to cues from their space-flight environment, as compared to worms that are aging and are not space-flown. By utilizing this model organism, the researchers demonstrated through a few experiments that biological aging is, in fact, affected by space flight, just as Albert Einstein had predicted.

Comment on "Science PhD Career Preferences: Levels, Changes, and Advisor Encouragement"

Recently an article was published by Saeurmann and Roach in PLoS ONE, entitled, "Science PhD Career Preferences: Levels, Changes, and Advisor Encouragement." Here's the link to their article:

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036307

This article examined how many PhD students in the sciences become less enthused over the course of their PhDs about staying in academia after graduate school. It seems that there are more and more PhD students who want to pursue "alternative careers," like working in industry or government instead of doing academic research.

As a biology PhD student, I agree with the authors that there should be additional "mechanisms" to prepare PhD students for pursuing these alternative careers that can complement the advice given by a thesis advisor to stay in academia. However, I would also like to point out that not all professors assume that PhD students will also want to become professors, and that academic researchers can also be knowledgeable about alternative careers outside of the "university ivory tower," such as if they start a biotech company or the like.

Additionally, I do not think it is necessarily "bad" that PhD students are exploring careers in different settings outside of academia; I think that we acquire many skills during our graduate education that would be extremely useful for working in government, industry, law, publishing, or other kinds of careers. What needs to change is how PhD students can identify these essential skills that can be transferred outside of the laboratory, and how these skills can be properly marketed.

For example, here is a list of some of the major skills any PhD student will have acquired by the end of his/her graduate education, which could be a great skill set for many different types of careers:

1. Teaching courses at the undergraduate, graduate, or other levels (like mentoring a younger student): developing assessments, grading assessments, organizing lesson plans, lecturing, leading discussions, etc.
2. Writing and revising manuscripts and designing figures for publication in peer-reviewed journals: primary research (summarizing your new contributions to the field) or reviews (summarizing everyone's research and the history, current status, and future directions of the field).
3. Presenting data in a variety of different settings: group meetings, departmental meetings, PhD committee meetings, traveling to small or large conferences - each presentation needs to be tailored for these different types of audiences.
4. Applying for grants or fellowships: this also involves tailoring your research description and plans for future research depending on the types of funding that are available.
5. In addition to presenting and writing about their work, graduate students also spend a great deal of time critiquing and examining others' work, either in their field of study or in a completely different field; it's extremely important to be knowledgeable and the most up-to-date in a particular topic, as well as to be wary of any competitors.
6. Working in a laboratory on a daily basis involves creating an independent schedule, planning ahead by the hour, day, week, or month (each type of experiment may require a different length of time), analyzing data, interpreting data, envisioning possible outcomes or potential explanations for unexpected outcomes, and constantly re-organizing your schedule to adjust for these outcomes.
7. Time management for dealing with 1-6 above, all of which is usually done on a daily basis.

It's All Greek to Me!

As a Greek-American, I found that it was easier for me to learn "scientific jargon" that may have been intimidating for my fellow classmates because so many scientific words are derived from the Greek language! As Toula's father in my favorite movie, "My Big Fat Greek Wedding," would say, "Give me a word, any word, and I will show you that the root of that word is Greek." He even managed to explain how the word "kimono" is actually a Greek word! (It was a clever attempt.)

I should also mention that while many scientific words have Greek roots, there are also many that have Latin roots (including the word "science" itself). However, the benefit of knowing Greek roots of scientific words is that Greek is still a language spoken today! At the same time, if you are familiar with a Romance language like Spanish, then sometimes you can still understand Latin roots of words without knowing Latin: one of my favorite examples is that the word "vaccine" is derived from the fact that the first actual vaccine that was administered was to give people cowpox, in order to create an immunity for the much more severe smallpox; in Spanish, the word for "cow" is "vaca", so that's how you can understand the origin of "vaccine"!

Below I have listed some of my favorite examples for Greek roots of scientific words. It's interesting to note that some of these words have Ancient Greek origins and are not based on the Modern Greek translation; also, the pronunciation in Greek is usually quite different than how we say the word in English:

1. "eco-": This comes from the Ancient Greek word "oikos," which means "home" (the modern Greek word is "spiti").
2. "-logy"": This is derived from the word "logos," which means "word"; so when you think about "ecology," this really means that we are studying the "home" of all living things, which is the natural world around us.
3. "chrome-" or "chromato-": These are derived from "xroma" and "xromata," which mean "color" and "colors."
4. "proto-" and "deutero-": These words come from "protos" and "defteros," which mean "first" and "second." My favorite words in developmental biology are "protostome" and "deuterstome," which refer to animals where the mouth develops either first or second; since "stome" comes from "stoma," which means "mouth," this is a pretty easy translation from Greek!
5. "heme-": This comes from "aima", which means "blood."
6. "helio-": This comes from "ilios", which is "sun" (nuclear fusion occurs on the Sun, which is when 2 hydrogen atoms are combined to form helium, so that's how "helium" got its name; "hydrogen" got its name because "hydra" means "water" - modern Greek word is "nero" - and there are 2 hydrogen atoms and one oxygen atom in a molecule of water).
7. "atom-": This is an interesting one: it is derived from "a" and "tomos," which basically means "uncuttable." Also, these words are the basis for another Greek word, "atomo," which means "individual." Now it makes sense why an "atom" was described as the smallest unit of matter!
8. "erythro-" and "leuko-": "erythro-" comes from "erythros," which means "red" (modern Greek word is "kokkinos"), and "leuko-" comes from "levkos," which means "white" ("aspros" in modern Greek"); now it makes sense that erythrocytes are red blood cells and leukocytes are white blood cells, right?
9. "telo-": This word is derived from "telos," which means "end"; it's no wonder that "telomeres" are the segments of DNA at the ends of chromosomes ("chromosome" comes from "chroma" and "soma", meaning "colored body," which is how chromosomes were described when doing karyotypes, and "karyotype" has the root "karidi", which means "nut" because the nucleus was thought to look like a nut - see, this can go on and on forever!) , and also "telophase" is the final part of mitosis ("mitosis" comes from the word "thread," referring to the thread-like spindle that forms to separate the chromosomes to either side of the cell; interestingly, "meoisis" comes from the word "subtract" because you end up with half as many chromosomes - again, this can go on forever!)
10. "-graph": This comes from "grafo," which means "to write" (although today we make graphs on the computer!).
... and many, many more!

Comment on "The Top 10 Worst Things About Working in a Lab"

I recently saw an article on the Science Careers website called "The Top 10 Worst Things About Working in a Lab", written by Adam Ruben. Ruben is a very talented writer and has done a great job with this article; it's both amusing and informative! Here's the link: 

http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_01_27/caredit.a1200012

I thought I would comment on a few of the "Top 10" that Ruben has discussed in his article:

"10. Your non-scientist friends don’t understand what you do."

All scientists have to agree about this one: there is so much to investigate and so many questions to answer when working in a lab, which means that your project should be extremely narrow and specific; however, this also means that only you and a few other scientists will understand what the project is! Even when two scientists from completely different fields have a conversation, they need to start out with some basic explanations about their research before getting into a more complicated discussion. In any case, even if your non-scientist friends and family members do not understand what you are studying, that doesn't mean they cannot appreciate the work that you do or even understand a basic explanation of your research. I think it is actually quite crucial that scientists learn to explain their research so that non-scientists can understand, as well! Even just practicing how to describe your work in one sentence is a challenging but rewarding experience. It's also important to realize that if your research is not going to immediately solve some human disease, then it's necessary to explain why your work is still relevant. However, I believe that, as a biologist, understanding the complexity of all living things is extremely relevant to begin with!

"7. Sometimes experiments fail for a reason. Sometimes experiments fail for no reason."

It's definitely hard for a non-scientist to understand that things just don't work, and you simply don't know why! Since we are constantly performing experiments with many different variables that could account for something "not working", and we don't have the privilege of being able to see all of these variables with the naked eye, troubleshooting can be extremely time-consuming and arduous. However, this can help explain why repeating experiments multiple times is so crucial, simply because something could work and then not work and then work again, so you need to know if a result is actually "real"! An optimistic point of view would also be that even if you get a negative result when expecting a positive one, this could still be an important finding! The difference between hypothesis- and exploratory-driven science lies within this logic, as well.

"6. Your schedule is dictated by intangible things."

Scientists never have had and never will have a regular 9 to 5 job - on a daily basis, we are not dealing with other people who work from 9 to 5; we are dealing with things that need to incubate for 6 hours or timecourses that need to be examined every 3 hours, which means that a normal work schedule is not likely!

Science in the Movies

As both a scientist and an avid movie-goer, I always feel the need to comment on how movies portray scientists or discuss scientific issues in general. Although I never read any of the comics, I have enjoyed watching many of the recent movies that have been adapted from Marvel and DC Comics, and I am always amused by their "take" on science:

1. For some reason, scientists are always trying to destroy the world, and that's why we need superheroes to save the world; was every scientist tormented in school for being "nerdy", which is why they now hate all of humanity?
2. Scientists are either extremely attractive or extremely unattractive; there's no in-between. One example is Peter Sarsgaard's character in "Green Lantern" - the receding hairline, huge forehead and bushy eyebrows really does the trick.
3. Scientists always wear white lab coats all the time, even when they aren't doing science.
4. Scientists are extremely smart, but somehow this intelligence is too much for their own good. Better yet, they are extremely smart building whatever they are building until it is time to show off the new invention, and then somehow everything goes completely wrong and their intelligence is no longer useful to solve the problem - only a superhero can save the day (like Dr. Octavius from "Spiderman")
5. In terms of the accuracy of scientific concepts, we can all agree that this is not the main concern for the plot of any of these films. However, in "X-Men", for example, I still think it's worth pointing out that an individual human cannot immediately evolve, only a population can evolve over time, and that a mutation is not necessarily a bad thing (and a mutation would never result in something not relevant to human evolution, like the ability to bend metals)