The Science Behind the Image Contest Winners: Fluorescent Muscles in Living C. elegans

The BPS Art of Science Image Contest took place again this year, during the 61st Annual Meeting in New Orleans. The image that won third place was submitted by Ryan Littlefield, assistant professor, Department of Biology, University of South Alabama. Littlefield took some time to provide information about the image and the science it represents.

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How did you compose this image?

Usually these C. elegans worms move around quite vigorously.  I added muscimol to prevent muscle contraction.  I picked three different types of worms that appear red only, green only, and red and green (which appear mostly yellow) and mixed them together on a thin pad of agarose.  The worms in the image all happened to clump together, resulting in a nice demonstration of the different color patterns.  I collected Z-stacks for each of the fields of view on an Andor spinning disk confocal microscope.  Using ImageJ software, I then made projections for the images that included the body wall muscle of the worms and pair-wise stitching of about six different projections.

What do you love about this image? 

The juxtaposition of all three types of transgenic worms being next to each other was very striking. The image includes all the different regions of the worms in various orientations, shows many of the different muscle types in these worms, and shows how the muscle cells fit together.

What do you want viewers to see or think about when they view this image?

The striated myofibrils in these worms are beautifully organized along their lengths, and it naturally raises the question of how this organization is achieved. In addition, the different muscle types show the viewer that there is a lot of diversity along the length of these 1mm worms.

How does this image reflect your scientific research?

I am interested in how actin and myosin become organized into functional, contractile bundles. In particular, I am interested in how actin filament lengths are specified in striated muscle.  In these worms, I modified an isoform of muscle myosin and tropomodulin with fluorescent proteins (mCherry and GFP, respectively) to determine how thin filaments are organized within these muscles.

What are some real-world applications of your research?

Both the uniformity of and specific lengths of actin filaments are important components of muscle physiology. Misregulation of actin filament lengths may be important factor in diseases including cardio- and skeletal and myopathies.  In addition, muscle damage from extended spaceflight, sarcopenia from aging, and acute muscle injuries may be slowed or prevented by interventions that prevent actin filament lengths from changing.

How does your research apply to those who are not working in your specific field?

Striated myofibrils are a dramatic example of a dynamic, self-organizing biological system that is attuned to a specific function (contraction).  Similar mechanisms for functional self-organization may also be used for other contractile actomyosin bundles, such as stress fibers and contractile fibers in smooth muscle, and for other dynamic cytoskeletal systems, such as flagella and microtubules in the mitotic spindle.

Get to Know: Bert Tanner, BPS Early Careers Committee Chair

We recently spoke with BPS Early Careers Committee Chair Bert Tanner, Washington State University, about his research, his time on the committee, and the years he spent as a gymnast.

tanner-bertWhat is your current position & area of research?

Assistant Professor, Department of Integrative Physiology and Neuroscience, Washington State University

I study muscle biology and teach physiology to undergraduate, graduate, and veterinary students. Research studies within my laboratory focus on normal, mutated, and diseased proteins that influence muscle contraction. We often integrate mathematical modeling, computational simulations, biochemical assays, and biophysical system-analysis to investigate complex network behavior among muscle proteins. We use these findings to describe and illustrate molecular mechanisms of contraction that underlie muscle function at the cellular and tissue levels.

What drew you to a career as a biophysicist?

I studied Physics as an undergraduate student at University of Utah. The last couple years of my undergraduate studies I got the opportunity to further explore bioengineering and computer science, and I participated in a summer research experiences learning about computational biology, remote sensing, and environmental biophysics. Through these experiences, I became increasingly interested at using mathematics, physics, and computation to better understand and describe biological processes. Through a series of injuries, I started learning more about physiology and became increasingly curious about different applications where mathematical modeling could help illustrate complicated, dynamic processes at the molecular, cellular, and organismal levels.  This led me back to graduate school, where I ultimately began studying muscle biophysics.

What do you find unique or special about BPS? What have you enjoyed about serving on the Early Careers Committee?

I love the rigor, diversity, and plasticity of the Biophysical Society, as well as the annual Biophysical Society meeting.  I’ve been attending and presenting at the national meeting since 2004, and I am really impressed by the high-quality science and constructive engagement of many society members—many of whom have become great friends and colleagues over the years. I also really appreciate the strong commitment to training young scientists in a rigorous, difficult field that is demonstrated by the BPS and its engaged membership. I enjoy being a member of the Early Careers Committee because it is a platform that enables education and programming for early career biophysicists via the newsletters, society webpage and blog posts, and annual meeting events.  These early career biophysicists are among the best and the brightest minds in the world, and our committee feels it is critical to help them learn about the myriad career paths where their skills will make an impact: academia, industry, small business, national laboratories, science writing and education, public policy, etc.

Who do you admire and why?

I admire many people from many different walks of life, but I often think most of the people that have impacted my education in a positive way. This includes a handful of teachers from elementary, middle school, and high school, all of whom made a really big impact on my thinking and career choices. Just like the impact these teachers made on me, other teachers work tirelessly to educate students each day; the well-being of our society greatly benefits from their efforts.  A second tier of people that I really admire are the approachable, engaging, unselfish, and constructively-critical mentors or colleagues that I get to interact with each year.  These people inspire me to try and do my best each day, and to treat people kindly.

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What do you like to do, aside from science?

I love the outdoors and to exercise. When I can pair these two up, it is even better.  My favorite hobby is skiing, just being out in the snow and gliding down the mountain, trail, or path is fantastic.  The past few years I’ve spent all my spare skiing-time on the ‘magic carpet’ teaching my son how to ski.  He is 5 now, and getting pretty good at the ‘blue squares’.  On our last ski day in Spring of 2016, my daughter (then about 18 months old) even skied by herself for about 60-100 feet.  She loves skiing and spent most of her first couple seasons skiing in a backpack on my back. I cannot wait to watch her keeping up with her big brother soon.

What is your favorite thing about living in Washington?

The diversity of the outdoor activities.  My family and I get to live in a small town and I get to work at a Pac-12 university with wonderful colleagues and great resources to pursue my research.  However, we are only 30 minutes to 2.5 hours away from world-class white water rivers, camping, hiking, backpacking, and pretty good skiing.  This accessibility to nature, and the diversity of options is really special to me and my family.

What is something BPS members would be surprised to learn about you?

I was a gymnast until age 18.  I loved it, but it took a lot of time and I decided not to pursue it as a collegiate athlete.  However, it was pretty fun watching some of the fellow gymnasts that I’d trained with, and competed against as I grew up, perform in the Olympics over the past 15-16 years.

Do you have a non-science-related recommendation you’d like to share (book, movie, TV show, etc.)?

The recent Zootopia movie has a classic and wonderfully painful scene with sloths running the DMV.  For a quick laugh (2-3 min segment) you should check it out on YouTube.

Molecular Mechanics & Asthma

May has been designated Asthma Awareness Month by NHLBI and the Asthma and Allergy Foundation of America. The World Health Organization estimates that 235 million people worldwide suffer from asthma. The Biophysical Society is taking this opportunity to highlight how advances in basic research contribute to our understanding of this disease. BPS member Anne-Marie Lauzon of the Meakins-Christie Laboratories of the Research Institute of the McGill University Health Center studies the role of specific proteins in determining the contractile properties of smooth muscle, in particular as they pertain to the problem of airway hyperresponsiveness in asthma.

Figure Lauzon-Asthma

What is the connection between your research and asthma?

Asthma is an inflammatory disease characterized by airway hyperresponsiveness, an exaggerated bronchoconstrictive response to various stimuli. Because airway smooth muscle (ASM) is the final effector of bronchoconstriction, it is commonly believed to be hypercontractile in asthma. This paradigm is supported by animal models but has never been demonstrated in human airways. We measure the biophysical properties of asthmatic and control human ASM to determine whether or not it is hypercontractile in asthma. We study the ASM bundle mechanics as well as their molecular mechanics in order to elucidate what is abnormal with asthmatic ASM. Molecular mechanics measurements allow us to investigate the mechanisms of ASM contraction and also provide us with additional tools to measure the mechanics of ASM in airways too small to be dissected and studied at the bundle level.

Why is your research important to those concerned about asthma?

Even though asthma was first described in the 1860s there is still no cure. Current medications alleviate and control the symptoms but there is still no therapy, no doubt because of our lack of understanding of the exact causes and mechanisms responsible for asthma.  Millions of Americans suffer from asthma and environmental factors worsen those numbers every year.  In addition to the poor life quality of asthmatic subjects, in some cases asthma can be fatal.

To date, most research on asthma has focused on the inflammatory aspect. Few laboratories address the ASM mechanics in asthma and even fewer address it directly in human samples. Along with my collaborators at the Meakins-Christie Laboratories of the Research Institute of the McGill University Health Center, we address the effect of inflammation on ASM mechanics from the whole human subject to the intracellular molecular motor level. This multi-scale approach allows us to verify at given scale levels theories developed at other levels.

How did you get into this area of research and how long have you been working on it?

As an undergraduate student doing a double major in Physics and Physiology at McGill University, I got very interested in the rheology of air and blood flow. Montreal counts several world renowned laboratories that perform pulmonary research so I had the chance of getting involved quite early on in pulmonary mechanics studies. Then, I pursued at McGill University a Ph.D. addressing the time course of bronchoconstriction, followed by a post-doctoral training at the University of California, San Diego, where I studied the distribution of pulmonary ventilation in weightlessness. A second post-doctoral training at the University of Vermont allowed me to specialize in the molecular mechanics of contractile proteins.  In July 1998, I was recruited back to the Meakins-Christie Laboratories to start my research on the mechanics of human ASM in asthma.

Do you receive public funding for this work? If so, from what agency?

My research is currently funded by the Canadian Institute of Health Research, the Réseau en Santé Respiratoire du Québec, and the Natural Science and Engineering Research Council of Canada (funding for the basic aspect of smooth muscle contraction). I was also recently part of a multi-PI research group funded by the National Institutes of Health (NIH).

Have you had any surprise findings thus far?

The biggest surprise that we have had so far in this research is that even though asthmatic ASM is commonly believed to be hypercontractile, it is not at all easy to demonstrate its altered mechanical properties. We started our investigations with the trachealis muscle because of its ease of dissection and we found that it behaves exactly the same in asthmatics and in controls. Because we previously showed in rat models of asthma that inflammatory cells can enhance ASM mechanics, and because more inflammatory cells are found in the peripheral airways than in the trachea, we concluded that the trachealis muscle was probably not representative of peripheral ASM mechanics. This later fact was verified in a horse model of asthma, the horse with heaves, in which we showed a perfectly normal trachealis in horses with hypercontractile peripheral ASM. Repeating these studies with human peripheral airways is however not a simple task, but it is the main endeavor of my current post-doctoral fellows Gijs Ijpma and Oleg Matusovsky and research assistants Nedjma Zitouni and Linda Kachmar.

What is particularly interesting about the work from the perspective of other researchers?

Our thorough characterization of the mechanical properties of asthmatic ASM will delineate the relative importance of other mechanisms also potentially responsible for airway hyperresponsiveness and asthma. Such other mechanisms include alterations in airway-parenchyma inter-dependence, neural control, surfactant properties, etc.

What is particularly interesting about the work from the perspective of the public?

Getting a better understanding of asthma will take us one step closer to potentially curing it, but at a minimum, of finding better relief medications.

Do you have a cool image you want to share with the blog post related to this research?

See the figure at the beginning of this post. Airway tree section from a control (A) and an asthmatic (B) subjects in which the actin is stained with TRIT-C phalloidin thus, showing primarily the airway smooth muscle. Airway cross-section of a control horse (C) and a horse with heaves (D), a disease very similar to human asthma. (E) A dissected smooth muscle strip hooked up in an organ bath for mechanics measurements.