Microbiology beyond the micrometer

by Reed Stubbendieck (@bactereedia)

Fig1
Figure 1. Light Microscope from the late 1800s. Photo credit: Reed Stubbendieck, Personal Collection.

If I asked you what the signature tool of a microbiologist is, you would likely respond: the microscope (Fig. 1). Not only do the field and instrument share the prefix micro (from Greek mikrós, meaning “small”), but the development of microscopy established the field of microbiology. In the mid-seventeenth century, Robert Hooke and Antonie van Leeuwenhoek built the first microscopes. Using his microscope, Hooke provided the first description of a microorganism when he reported on the fruiting bodies of fungi and coined the term “cell” in reference to the structures that he observed in cork. Meanwhile, van Leeuwenhoek was the first individual to observe protozoa and bacteria, which he called “wee animalcules”.

Born from the observations of Hooke and van Leeuwenhoek, generations of microscopists have used the microscope to study the structure and substructures of cells, observe proteins in motion, and diagnose diseases, among many more applications (Some of which I’m sure Scott will explore in future posts). Thus, since the inception of microbiology, it has been difficult to disentangle the field and the instrument. However, microbes are not confined to the micrometer scale and hidden beyond our eyesight. In this post, I would like to highlight some examples of microbes that you likely encounter in your daily life and are visible with your naked eye.

Fig2
Figure 2. Mushroom fruiting bodies. Photo taken in East-Central Texas by Reed Stubbendieck.

Some of the most obvious examples of macroscopic microbes are fungi and include the beautiful mushrooms that bloom near the trunks of trees in our yards and forests (Fig. 2). But given that antibiotics are one of my primary research interests, I’d be remiss if I didn’t highlight the humble bread mold Penicillium. Who among us hasn’t kept a loaf of bread for a little too long, only to discover an unexpected fuzzy blue-green growth (Fig. 3A)? Likely, we write off the loss, toss the loaf, and head to the grocery store to acquire more bread. However, this contaminant is among the most important microbes ever discovered! In 1928, spores from this mold contaminated a Petri plate in Alexander Fleming’s laboratory and produced a region where bacteria were unable to grow (called a “zone of inhibition”) (Fig. 3B). Later on in 1940, Fleming’s observations inspired the chemists Ernst Chain, Howard Florey, and Norman Heatley to develop methods to mass produce the active agent from the mold. The result of their work was the antibiotic penicillin (Fig. 3C), which was likely the single most important advancement in modern medicine. Not a bad cost for a missed sandwich.

Fig3
Figure 3. The bread mold Penicillium produces antibiotics. (A) Moldy bread covered in Penicillium. Note: this is a stock photo and not a picture of my own bread (B) Penicillium inhibits the growth of the pathogen Staphylococcus aureus on Petri plates. (C) Core structure of penicillin. The R group is variable and distinguishes different types of penicillins. Photo credits: Panel A: Wikipedia user Henry Mühlpfordt  under the GNU Free Documentation License, Version 1.2. Panel B: Christine L. Case, Ed.D.

While antibiotics treat our infections, the yeast Saccharomyces cerevisiae helps feed the body and soul. To simplify an introductory course in biochemistry, when yeast consumes sugars but is starved for oxygen, it produces carbon dioxide gas and ethanol as byproducts of its metabolism. We use the former to make our bread rise and the latter to give our booze its buzz (Fig. 4A). But that’s not all, together the interactions of yeast and bacteria give sourdough bread its signature tangy acidic taste (Fig. 4B), form the biofilms that make up the rinds of cheese (Fig. 4C), and provide starters for Kombucha tea (Fig. 4D) (see here for more information).

Fig4
Figure 4. Fermented beverages and foods. (A) Homebrewed wheat beer in fermenter showing Krausen, the foamy head that consists of yeasts and wort protein, at the air-liquid interface. (B) Sourdough starter showing carbon dioxide bubbles after feeding. (C) The rinds of cheese wheels are a mixed bacterial and fungal biofilm. (D) Kombucha tea with pellicle at the air-liquid interface. Photo credits: Panels A and B: Reed Stubbendieck. Panel C: Wikipedia user Myrabella under a CC BY-SA 3.0 license. Panel D: Graciously provided by anonymous.

Outside the kitchen, microbes also live together symbiotically and produce amazing structures. For example, the lichens that cover rocks, tree trunks (Fig. 5A) and gravestones (Fig. 5B) are made up of algae, cyanobacteria, ascomycete fungi, and even yeasts living together! Within nature, symbiosis is the name of the game.

g3053
Figure 5. Lichens. (A) Lichen covering a tree trunk in Wisconsin. (B) Lichens growing on a gravestone. Photo credits: Panel A: Reed Stubbendieck. Panel B: Brian Robert Marshall under a CC BY-SA 2.0 license.

One of my favorite symbiotic systems is studied by my current laboratory and involves  fungus farming ants, the fungus they cultivate (called the cultivar), and a symbiotic bacteria called Pseudonocardia. These ants cut leaves and other plant material (depending on the ant species), but the ants do not eat the leaves. Instead, the ants feed the leaves to their fungal crop, which they consume it as their sole food source. Because the fungal cultivar is maintained asexually with limited opportunities for genetic recombination, it is not genetically diverse and is susceptible to pathogen infection. One pathogenic fungus is called Escovopsis and it is only found within the fungal gardens. The Escovopsis can overgrow and consume the fungal crop. To prevent this infection, the ants use grooming behaviors and form a symbiotic relationship with bacteria called Pseudonocardia, which produces antifungals that inhibit the growth of Escovopsis but are not harmful towards the fungal cultivar. The ants have evolved specialized structures to house and feed the Pseudonocardia on their exoskeletons and some ants, such as Acromyrmex sp. cf. octospinosus, can become totally covered by their symbiotic bacteria (Fig. 6)!

(Note, I will almost certainly cover the relationship between fungus-farming ants and Pseudonocardia in more detail in a future post.)

77652397-cf_octospinosus6
Figure 6. Symbiosis between ants and bacteria. Acromyrmex sp. cf. octospinosus worker ant covered in white symbiotic bacteria. Note the chewed leaves in the fungal crop. Photo credits: Alex Wild, purchased for use on this website.

Finally, should you find yourself in orbit over Earth, please find comfort in the knowledge that you can still revel in the beauty of our microbial world. Satellite photographs from NASA have captured images of massive blooms of algae in our planet’s oceans and seas!

1280px-Bloom_in_the_Barents_Sea
Figure 7. Algae bloom over the Barents Sea. This photograph showing a large algal bloom was taken by the NASA Aqua satellite in 2011.

This post has barely covered the diversity of microbes in our world, but I hope it has convinced you to leave the microscope behind and look for examples of microbes in your daily life. Check your showers for the pink-colored Serratia marcescens, observe a lovely mushroom on your lawn, or  overturn a rock and find a lichen. I would love for you to share your pictures with me! Use the hashtag #macromicrobiology and be sure to tag @bactereedia and @SciSidequests in your post.

 

If you’re interested in checking out more beauty in the microbial world, I highly recommend the book Life at the Edge of Sight by Scott Chimileski and Roberto Kolter and the corresponding museum exhibit at the Harvard Museum of Natural History.

What’s Good for the Goose is NOT Always Good for the Gander

by Andrew Anderson  (@AndersonEvolve)

To start this post, I feel the need to point out that I detest Naturalistic Fallacies (i.e., what’s natural is morally good), and the situations I will describe can be sensitive to some readers.  These situations occur in nature and in no way do I think (and no one should think) that they justify disgusting attitudes and behaviors seen in our society. If you do not wish to read those descriptions, they will be in blue text so you can skip them.

apogon-doederleini1
Four-line Cardinalfish–A mouthbrooder that will engage in filial cannibalism.

One of the more interesting aspects of sex-roles and sexual selection is the concept of sexual conflict.  Put simply, sexual conflict is whenever a trait or action benefits one sex over the other. There are two kinds of conflict, the first is called intralocus (within location) conflict.  A rather humorous example is the thought,“why do males have nipples?” The genetic architecture for nipples, and milk delivery in general, is vital to the survival of mammals. A female without nipples would not be able to deliver milk to her offspring and would not have any successful offspring (since they didn’t make it past birth).  Disentangling male and female expression of traits can take some evolutionary time, but more importantly, a mutation that stops nipple formation is very costly unless it occurs in males only.. Further, as the presence of nipples doesn’t impose a much of cost (survival or energetic) to males, they’re just there. However, milk delivery is more costly, so evolution can act with a little more intensity to separate the sexes, so males don’t have those as fully developed.  The mechanism for the male/female expression is hormonal control, thus a male given a female hormone will start to express those traits. Another example is secondary sex traits. Bright, large feathers in peacocks are energetically costly and make them more vulnerable to predators, peahens would do well not to express those traits. Thus the architecture for the feathers is different for males and females, again this mostly done by hormonal control.

The second kind of conflict is interlocus (between location) conflict.  This is usually when males or females engage in behaviors that are self-beneficial but potentially harmful to the other sex. 

Examples of interlocus conflict can be found in insects, some species have evolved brushes to scrape out rival males’ sperm or plugs to prevent other males from mating.  Clearly, the benefit to the male is the ability to reduce his mating competition without guarding the female, but these mechanisms can damage the female and prevent her from mating with a male she might deem more suitable or prevent her from being ever able to mate again even after she lays her eggs.  Male water striders have evolved hooks to grab females and hold themselves in place to complete copulation. Ducks will actually force copulation with a female in a bid to put their genes into the next generation. While biologists focused on the male behaviors at first (they’re more visible and there has been a bias on male traits since historically science is male dominated), we’re learning more and more that females are engaged in an arms race themselves.  Females can chemically “help” certain males’ sperm and have evolved ways to resist damage (insects), become bigger and stronger to shake males (water striders), or evolve complex vaginas to shunt away a male’s sperm who forces himself on her (ducks).

Okay, okay.  You know what’s coming next if you’ve been keeping up with me… FISHES!  Again, I’m going to focus on brood care. In my lab, others have shown that male pipefish (check my first post about them here) actually will provide more care to some female eggs over others.  Pipefish males actually exchange resources with the eggs they are brooding (similar to mammalian pregnancy) and it has been shown that some eggs are reduced during pregnancy.  This means that males can actively take resources from the eggs the female provided. Larger females produce more eggs and can completely fill a male pouch making a good return on investment for the male.  Males tend to prefer larger females and will reduce a larger portion of eggs from small females, presumably to gain energy to invest in future pregnancies with large females. Thus, a small female has spent relatively more resources on reproduction only to have a low amount actually born.

  One of my favorite examples outside of pipefish are the cardinalfishes (Apogonidae), which actually engage in filial cannibalism.  Cardinalfishes engage in male mouthbrooding, a process which is costly to males. They cannot eat until the eggs are hatched. Since they are investing in a brood they want to maximize that investment.  If a female produces a small egg mass, the male may actually consume the entire brood in one gulp, especially if he encounters another gravid female and he has not been brooding long. While this is an amazing feature, what’s even more mind-blowing is some cardinalfishes the females have evolved a response.  They don’t fully develop some eggs (saving energy), but include those eggs in the masses they give to the male, so the mass seems like it has more eggs and the male would be less likely to consume it.

 The world of sexual selection and fishes is wild and weird and there’s nothing quite like it!        

 

The VERY SCIENTIFIC Model Organism Alignment Chart

model alginment(Images from wikipedia.org)

by David Green (@GradDavid_Green)

Science is a collaborative effort. Graduate students, professors, technicians and more all have to come together with a single purpose in the lab. We would be remiss to forget the silent hero of every biology lab, the organisms we study. However, not all organisms are created equal. Through very mild debate with my colleagues at Scientific sidequest I have answered the most important question of our time. What is the DnD alignment of different model organisms. I have shared my rationale below, think I’m crazy? Wondering where fruit flies are? Come find me on @SciSidequests and fight me!

Lawful Good: Dog – Lawful good is exemplified by its compassion, honor, and sense of duty. We would be remiss not to give the nod to man’s best friend on this one. Not a common model organism by any means, but important for the work they are involved in. Some examples being the study of diversification between different breeds and the use as medical models for muscular dystrophy. Dogs continue to loyally help humans out on the science side of things as much as they do at home.

Lawful Neutral: Rabbit – Lawful neutral show a strong dedication and loyalty. No matter what you study in science, it is quite likely that rabbits have been helping you out in the background. One of the greatest sources of polyclonal antibodies. Without their help, research across all the models would be seriously impacted.

Lawful Evil: E. coli – Lawful evil are bad natured but always following the rules. Incredibly powerful and with the right strains incredibly deadly. Escherichia coli  represents the best and worst of the model organisms. Incredibly simple to use and grow and an important player in almost any lab due to its ability to shuttle plasmids which allow the storage of DNA. You could probably chug a liter of the attenuated strains and come out fine (though I do not recommend it, the smell is. unique). However, as many salad lovers have learned in America lately, the right wild strains will kill you dead. Willing to help for the right price (lots and lots of food), but always with a dark side. E. coli earns its place as our lawful evil model organism.

Neutral Good: ArabidopsisAlways willing to help, but not beholden to anyone;0ur plant representative shows up here. Arabidopsis generally does not get grouchy or upset and it’s unlikely to try to kill you. The Arabidopsis is willing to help you out in your science if you can keep them alive. Fantastic for studying both development and a slew of plant related questions, these small members of the mustard family are a great member of the scientific model family.

True Neutral: Zebrafish – True neutral does not feel strongly about anything. No one ever expects the zebrafish. Tiny small freshwater vertebrate, they have a plethora of genetic tools at their disposal but their unique genetics (they had a complete duplication of their genome unique to their branch of fish) makes engineering mutants much more difficult, though some would say interesting. The little buggers also will refuse to have sex for weeks whenever the most important deadlines are coming up and there is literally nothing you can do about it. Zebrafish don’t care about you, but they also don’t hate you. A true neutral.

Neutral: Evil Viruses – Typically, selfish and willing to turn on their allies, viruses are constantly changing, not just their behavior but their sometimes massive chunks of their genetic code. Not even living viruses survive through hijacking the cellular machinery of the cells they infect.

Chaotic Good: Yeast –  Our good friend yeast, though wild yeasts come in many varieties, the always faithful bakers yeast will always be present in our research labs. Powerful genetics, some unique tools, yeast is always willing to help, but mostly just likes chilling eating whatever it is they put in that broth.

Chaotic Neutral: Non-model organisms –  The Wild West of scientific models. For those brave researchers that are out there working on weird and wild things they find out in the world there is the non-model organisms. From pigeons to puffer fish they represent a wild and free world, not bound by the normal constraints of science or even a sequenced genome; the sky’s the limit with these freaky friends.

Chaotic Evil: Mice – Hate you and everything about your research. These cute little furry guys like to live their lives in a way to make research on them as difficult as possible. They require constant pampering and stimulation to stay happy in their cages, being mammals, they raise their young in utero making studying development incredibly hard. Plus they are nocturnal, so behavioral assays got you dragging your butt to work at 2am on a Sunday. Thanks mice. However, the siren call of the mammalian model will always draw more researchers into the dark halls of a mouse facility, got to chase that “in mammals” sentence in your next Nature title, eh?

 

What Does it Mean To Be a Biomedical Engineer?

By Scott Mattison (@FoolsPizza)

In typical engineer fashion, instead of introducing myself and my field, I jumped in head first and published a few more technical articles. I am a young professor of Biomedical Engineering, and one basic question I am often asked is, “What is a biomedical engineer?” Surprisingly, this is a much more difficult and nuanced question to answer than it may seem.

We can start with the technical answer: as with most fields, biomedical engineering is a very broad discipline and has many different sub-specialties within it. Biomedical engineers might design prosthesis, improve instrumentation for hospitals, work in pharmaceuticals, develop physiological models, and even research artificial organs.

Biomedical Engineering
A sampling of the many different sub-disciplines of Biomedical Engineering. The Biomedical Engineering Society does an excellent job discussing a lot of these disciplines.

To meet the broad demands of their field, many degree programs in biomedical engineering provide their engineers with a broad engineering background in their first few years of school gaining skills in electrical and mechanical engineering as well as biology. As they progress through their degrees, biomedical engineers begin to focus their education into increasingly specialized backgrounds, which gives them a strong knowledge foundation in many fields and enhanced knowledge in their specialty.

Obviously, education is really only a small part of what defines a field. In the workplace, engineers wear many hats. Biomedical engineers have the technical knowledge and skills to work in most specialized engineering fields (electrical, mechanical, etc.), but also have the medical and scientific knowledge to communicate with doctors and researchers. This means that biomedical engineers get to bridge the gap between engineering and practice and apply their skills to two equally exciting, yet fundamentally different, fields.

Now that the technical answer is out of the way, I want to convey the more practical answer to this question. There is always a unique distinction between engineering and science, and biomedical engineers walk this line more than most. The rationale for this distinction is that the typically science seeks to develop knowledge and understanding of the physical universe whereas engineering attempts to apply scientific knowledge to the needs of society. To me, the line between science and engineering is actually rather blurry. No work exists in a vacuum and someone seeking to developing knowledge is often going to have an application for that knowledge in mind.

Biomedical engineering is a prime example of the interdependence of science and engineering. Scientists discover exciting new information about physics, chemistry, or biology and engineers turn these discoveries into new technologies which further feed scientific discovery and apply those discoveries toward tangible benefits. No one can  guess where the next big discovery will come from, and seemingly insignificant finds in science can eventually lead to huge breakthroughs in engineering (and vice-versa). Of course, this interplay does not merely exist between engineering and science but among and within various fields of science, wherein all discoveries feed into our bigger understanding of the world.

While I could continue to elaborate about the importance of collaboration between fields, I admit that I have deviated from my initial question: What does it mean to be a biomedical engineer? As a biomedical engineer, I personally feel a calling to not only perform innovative research in the fields of biology and medicine, but also to enhance the capabilities of the research projects of my peers. This feeds into my work in biomedical optics, where I develop new optical systems to study processes that I find fascinating as well as attempt to provide my peers with novel ways to obtain information about micro anatomy and cell organization.

It should be noted that this is merely my personal definition and is not the only possible one. Nearly any path may eventually lead people to the field of biomedical engineering; indeed, my graduate school mentor has a Ph.D. in Chemistry, but is clearly a biomedical engineer. In reality, anyone who is using engineering design techniques and processes to solve challenges in the fields of biology and medicine is working as a biomedical engineer.

Arming Sharks with Laser Beams: A Warm Meal or Seared Meat?

by Scott Mattison (@Fools Pizza)

SharkwithLaser
An update drawing of our hypothetical shark. (Credit to @AndersonEvolve for correcting the number of gills a shark typically has)

Last time, we determined a theoretically useful wavelength (500 nm) for arming sharks with a laser beam. This wavelength was useful as it would provide a decent transmission range through salt water. There are still three more major challenges facing the successful completion of our design (and several other smaller ones).

Laser is actually an acronym for light amplification through stimulated emission of radiation. Stimulated emission is the release of a photon of light as an electron relaxes from an excited energy state back to a ground state after absorbing energy. This means that when one photon goes in, two photons come out, generating additional light. Stimulated emission was predicted in Einstein’s quantum theory of radiation, and the first laser was built in 1960 by Theodore Maiman.

Stimulated Emission
A simplified rendering of stimulated emission using two energy levels.

The big take away of stimulated emission is that to build a laser, we typically need electrons to be in an excited state. There are several different materials that can give light amplification through this method including glasses infused with rare earth elements, semi-conductor materials, dyes, and even various gases like carbon dioxide and Helium Neon.

There are important considerations for selecting  the type of laser for a specific application. In our case, we are going to be operating a laser in the ocean, without an easy method for retrieval. Fortunately, as we are subcontracting for an evil organization, money is not a major consideration. However, the movements of the shark and harsh conditions of the ocean would require a stable laser source, and we need this source to be fairly small, as we do not want the laser to interfere with the shark’s ability to swim. Most importantly, we want to be able to cook a fish from a distance. From the American National Safety Institute standard Z136.1, we can determine the maximum safe exposure for skin to a laser beam. We will assume that we want the fish to cook in under 0.1 seconds as both the shark and fish will likely be moving. This means that we will require a laser intensity of over 6 W/cm2 just to pass the safety threshold of laser exposure. Likely, a high powered diode pumped solid state laser could provide the power and stability we need at our target wavelength; however, there are still a few more issues to consider.

The second major challenge is building a laser that can actually cook a fish underwater. Lasers are excellent at providing targeted heating. That is what makes lasers great tools for precision cutting, which is why we have laser cutters and use lasers for targeted treatment of cancers. Unfortunately, despite what movies and television shows tend to depict (looking at you Big Bang Theory), this means lasers are not good at doing more than targeted heating. With a laser, the shark isn’t going to get a warm meal, instead it will simply sear meat in one location. In fact, if we increase the laser power to increase heating, we are more likely to cut the fish in half than actually cook it (think laser cutter). We could work around this using beam steering components, but even if we could steer the beam to hit the shark’s meal, our laser wouldn’t penetrate deeply enough into the fish without burning away the outer layers (this would also probably smell terrible).

If this wasn’t enough of a problem, our final challenge is powering this laser, underwater. A laser diode runs typically with no better than 20% efficiency. This means to output 1 watt of optical power, the laser requires 5 watts of electrical power. Obviously, to save energy (and increase competitive advantage), the laser would not be operating constantly and instead would use some form of motion tracking to switch on and off. Even under these conditions, the laser would require a very powerful battery in order to operate effectively. Currently, finding a  lightweight and durable power source that the shark can carry around  and provide a long enough operational lifetime to make the efforts worthwhile is a tough challenge. This might be the final deal breaker in our arming sharks with laser beams scenario.

So far we have really only discussed the large number of technical challenges to arming sharks with laser beams to provide a warm meal. We have completely ignored the ethical dilemmas (short answer: it’s bad) and whether the laser would even provide a competitive advantage to the shark (it won’t). Additionally, we haven’t even discussed how to actually arm the sharks with lasers. Based on this low level of analysis, we can conclude that following the ideas of a person who calls himself Dr. Evil might be a bad idea.