It helps to be flexible: disordered proteins in biological stress response

Imagine you are working on a project with a large group of people, all with different personalities and responsibilities. Your group was just informed that something important to the progress of the project went terribly wrong. Some people in the group start to panic, which causes other people to panic. There is no defined leader for this group project but you tend to take the lead during stressful times, so you quickly step up to the plate. You know that to get this project back on track, you first need to calm everyone down so that they can refocus on the tasks at hand.

Now try to imagine that instead of people, you and your group are large molecules composed of long chains of amino acids, a.k.a. proteins, and the group project is maintaining the life of your cell.

Much like a dollar bill must undergo many intricate folds to become an origami elephant, chains of amino acids must go through several steps to form a well-folded protein. Top image created by Chris Pielak

Proteins make up many important biological structures (such as hair, nails, and connective tissues) and carry out most chemical reactions in cells (such as converting food into energy or light into sight). For a long time it was thought  that proteins only function once they have “folded” into a highly-ordered shape, similar to how a flat sheet of paper folds into a smile-inducing origami elephant. The unique shape of a protein is dictated by chemical interactions between the amino acids that make up the protein as well as interactions between the protein and water. When drastic changes take place in the environment of the protein (i.e. during cellular stresses such as extreme heat, dehydration, or acidification), these important interactions are disrupted, which can cause proteins that are usually well-folded to temporarily unfold and become inactive. If such a protein remains unfolded for too long, temporary inactivity can become permanent as the protein becomes tangled up with other unfolded proteins in a process known as irreversible aggregation. Under extremely stressful conditions, a significant portion of the proteins in a cell can unfold and irreversibly aggregate, ultimately leading to cell death. So let’s keep all our proteins nicely folded, shall we?

Not so fast! In the past twenty years, the idea that a protein must be folded to function has been challenged by an up-and-coming group of proteins known as intrinsically disordered proteins (IDPs). As the name suggests, IDPs are defined by a distinct lack of a stable, well-folded structure, much like a single strand of spaghetti in a pot of water.

This cat knows spaghetti makes you feel better when you’re stressed out.

Interestingly, organisms across all domains of life have been shown to use IDPs to deal with environmental stresses. Many of these stress-response IDPs are “conditionally disordered”, meaning they can transition into or out of a more ordered state in response to an environmental cue. Given that IDPs are used to being in an unfolded-like state, it kind of makes sense that they can “survive” many of the environmental stresses that typically well-folded proteins can’t. But besides persisting through stressful times, how do IDPs help cells survive extreme environmental stresses? One emerging hypothesis is that stress-response IDPs work by morphing into a shape that can stick to partially unfolded proteins before irreversible aggregation can occur, thus making it possible for stress-sensitive proteins to refold after the stress goes away. In support of this idea, recent studies showed that the bacterial acid-sensing protein HdeA becomes disordered in acidic conditions, and it is in this disordered state that it can stick to partially unfolded proteins and prevent aggregation. Similar modes of action have been proposed for IDPs involved in heat- and dehydration-response as well.

So, just like you in the hypothetical scenario described at the beginning of this post, some IDPs keep the group project (the life of the cell) on track by pulling aside the easily stressed out group members (highly-ordered, stress-sensitive proteins) and calming them down a bit so that once the stress has subsided, everyone in the group can refold and get back to work.

Peer edited by Giehae Choi.

Follow us on social media and never miss an article:

A Scientist’s View of Animal Research

One of the most controversial aspects of biomedical research is the use of animals to benefit humans. Scientists use animals to test new treatments for human diseases and to understand human biology. Many groups have protested the use of animals for research. The most well-known and influential of these groups has been People for the Ethical Treatment of Animals (PETA). These groups have successfully raised concerns about using animals for research, and they have brought about changes such as closing down some research labs and decreasing the number of airlines that will transport animals destined for research. People perceive the benefits and detriments of these actions differently depending on whether they support or condemn animal use in research.

I am not writing this article from an entirely unbiased position because I work with animals to understand basic human biology and to discover treatments for human diseases. Since many articles about the negative aspects of animal research have been published, I intend to provide a more positive perspective on animal research from a scientist’s point of view.

The goal of using animals for research is to save human lives and improve human health.  Scientists do not use animals because it is fun, and they do not use animals when there are better alternatives (e.g. using humans, cell culture, or computer models). Scientists use animals for research because animal research can provide information to eliminate human diseases, improve health, and ultimately save human lives. Animal research has saved millions of human lives and has improved the health of billions more. Animals have played an important role in discovering cures for deadly diseases such as polio, smallpox, and hepatitis C. Animal research has also discovered treatments for Type 1 diabetes, malaria, cystic fibrosis, and thousands of other diseases.

Animal research improves animal health and finds cures for animal diseases. Animals contract many of the same diseases as humans do, such as heart failure and diabetes. Research in animals has saved the lives of millions of pets by providing vaccines, pacemakers, artificial joints, and chemotherapy for pets. Animal research has also improved our understanding of endangered species so that we can prevent their extinction.

Research in humans has limitations that can be overcome by using animals. Scientists and animal activists may ask why we cannot conduct all research in humans so that we can avoid the ethical dilemma of animal research. First, many studies are conducted in humans (over 100,000 people participate in clinical trials every year, and this number does not include the thousands more people involved studies that are not considered clinical trials). However, many studies are not feasible to perform  in humans. For example, studies involving diets or food components require subjects to be very compliant (follow the diet exactly) so that scientists can definitively answer their research questions (such as whether a vitamin or mineral is necessary for health). However, people are not usually very compliant with their diets, leading to confusing data and sometimes wrong answers to research questions. In animal studies, diets can be carefully controlled, which ensures that the data obtained is accurate. This allows scientists to answer very specific research questions about diet effects. Using animals for research also optimizes research funds by ensuring that research does not need to be repeated due to non-compliant human research subjects. Furthermore, research in humans is substantially more expensive than animal research, due to compensation for the research subjects and extra costs of research monitoring. Finally, humans have much longer lifespans than most animals, meaning that a single study could require 1-50X longer to complete in humans than in animals. This both raises research costs and increases the time required to make scientific discoveries.

Scientists prioritize animal health and minimize animal pain. When alternative methods of study, such as those in humans, are not an option, scientists use animals. Scientists undergo substantial training so that they know how to conduct research with animals in an ethical manner. Furthermore, before any animal research takes place, scientists must get approval for their planned study from the Institutional Animal Care and Use Committee (IACUC). This committee  includes at least one veterinarian, who ensures that the animals in the study are healthy and well. The committee also includes at least one person from the community who is not associated with the research institution. This ensures that animals used in experiments receive the maximum amount of care without interfering with the experiment. Every scientist must consider 3 words before they start working with animals: Replacement, Reduction, and Refinement. First, can the scientist replace animals with some other model? (For example, cells isolated from humans or animals or computer models). Second, can the scientist reduce the number of animals so that as few as possible are harmed? And third, can the scientist refine their experiments so that animals suffer as little as possible? All three questions must be addressed before research can begin.

While scientists may enjoy working with animals, they do not like causing pain for animals. Researchers ensure that the animals in their care are healthy and well for the research study. Many scientists are animal activists and whole-heartedly care for the animals they work with.

Science has a small impact on animals in comparison to animals harmed by other factors. Scientists in the United States used 12-27 million animals in 2010. Although this sounds like a large

A monument to the laboratory mouse in Novosibirsk, Russia

number, 99% of these animals are rats, mice, birds, or fish.  People in the U.S. consume more than 340 chickens for every 1 animal that is studied in a research facility. Furthermore, for every animal involved in research, another 14 animals are killed on roads.

Scientists and those who benefit from the science appreciate what animal research has accomplished. Scientists appreciate all that animals have done to benefit scientific advances and human health. A town in Russia raised enough money to erect a statue to pay tribute to all of the sacrifices that animals, namely the laboratory mouse, have paid to save human lives (see picture). This statue reflects the attitudes that scientists have for their laboratory animals, and it thanks them for what they have done to save millions of human lives.

Peer-reviewed by Caitlyn Molloy and Elise Hickman.

Follow us on social media and never miss an article:

Understanding Sea Turtle Navigation with Laser-based Imaging

https://www.maxpixel.net/Sea-Turtle-Is-Animals-2547084If you’ve ever been lost in an unfamiliar city or tried to walk around in the dark, then you may have found yourself wishing you had the eyes of a cat or the echolocation abilities of a bat. But have you ever wished for the navigation abilities of a sea turtle? While many animals are known for their superb sensory perception which make them better navigators than humans, it may surprise you to hear that sea turtles are among the elite navigators of the animal kingdom. Sea turtles are able to cross entire ocean basins (covering distances of thousands of miles) surrounded by seemingly featureless, dark water in order to return years later to their original nesting grounds. This behavior is as perplexing as it is impressive: while we know that sea turtle navigation has something to do with sensing Earth’s magnetic field, the mechanism which enables them to sense and interpret magnetic fields has not yet been identified.

To compare, humans have five senses. Each of these senses is linked to some kind of receptor which converts the environmental stimulus into a signal which our brains can interpret as either an image, a sound, a taste, a texture or a smell. For example, our eyes contain photoreceptors which convert light into electrical signals that travel to our brains and are interpreted as images. Sea turtles have another sense: they are able to sense magnetic fields. This means they must have some magnetic receptor which converts the magnetic field into a signal which is interpreted by the animal’s brain. However, scientists don’t know what these magnetic receptors are or where they are located within the body of a sea turtle. This is a crucial step on the path to understanding the impressive navigation abilities of sea turtles.

Working in collaboration with biologists who study sea turtle navigation, my research project is to design and build a special imaging system which is able to locate these magnetic receptors in sea turtles. This project can be broken down into three parts: design the imaging system, develop a method for detecting magnetic particles, then build and test the hardware.

Designing an Imaging System

You may wonder why it’s so hard to find these magnetic receptors if we know they must exist. It’s difficult because these magnetic receptors are extremely tiny, thought to be smaller than the size of a single cell, and they may be located anywhere inside the body of the sea turtle. The smallest species of sea turtle is roughly the same size and weight as a Labrador, with some species being several times larger, making the search for a cell-sized particle challenging. For an imaging system to detect these magnetic receptors, we need the following conditions:

  1. High resolution- Because these receptors may be very small, we need high resolution to locate where they reside within the tissue.
  2. High magnetic sensitivity- If we want to detect very small magnetic particles, then our system has to be very sensitive to small amounts of magnetic material.
  3. Fast- Because we have to search through large volumes of tissue, we need a fast imaging system to do this in a reasonable amount of time.
  4. Non-destructive- Many existing imaging methods require the addition of dyes and other contrast agents which irreversibly alter the tissue. We would like to avoid this because sea turtles are endangered and finding dead sea turtle tissue to image can be challenging.

So why can’t we use an imaging system that already exists? Although there are several imaging systems which are able to detect magnetic particles, none of them meet all four of our requirements. For example, magnetic resonance imaging (MRI) is very sensitive to magnetic material, but the resolution is not high enough for our aim. A microscope has really good resolution, but it can only image a very small section of tissue at one time, so the overall imaging speed is slow.

In order to meet all four imaging system requirements, we use a relatively new optical imaging system called Optical Coherence Tomography (OCT). OCT is very similar to an ultrasound, the same technology used to produce fetal sonograms.  Rather than using sound waves to form an image as in ultrasound, OCT uses light waves from a laser to create an image. By using light instead of sound, we shrink the scale of the imaging down so that our resolution is much better than that of MRI or ultrasound. By its nature, OCT is also non-destructive.

OCT works by illuminating the sample we want to image with light waves. When the light hits the sample, it can either pass through the sample or it can bounce away (we call this scattering). OCT captures the light that is scattered back in the direction from which it came. We record this light on a camera along with light that was reflected from a stationary mirror in a process called interferometry. By comparing the light reflected from the mirror and the light back-scattered from the sample, we can tell how far the light travelled after it was scattered from the sample. This allows us to create 2D images of the sample.

Developing a Method for Magnetic Particle Detection

To get the desired magnetic sensitivity, I designed and built an electromagnet which can produce a sufficiently high magnetic force. We place this magnet over the tissue we want to image. By applying a current with a sinusoidally varying amplitude to the electromagnet, we create a magnetic field with a sinusoidally varying amplitude. This variation in the magnetic field strength causes the magnetic force felt by a magnetic particle to vary sinusoidally as well. Therefore, any tiny magnetic receptors in the sea turtle tissue we are imaging will oscillate up and down in sync with the applied magnetic force. As the magnetic particles oscillate up and down, they will cause the surrounding tissue to deform. This deformation causes a measurable change in the back-scattered light. We record a series of images while applying the oscillating magnetic force. We can then compare consecutive frames to identify any pixels whose intensity is varying in sync with the applied magnetic force and by doing so, locate the magnetic receptors (see Fig. 2). An OCT system combined with this method of magnetic particle detection is called magnetomotive OCT.

https://users.physics.unc.edu/~aold/MethodsMMimaging.htm

Fig. 2 Schematic Diagram showing that when the magnetic receptors (black spheres) feel the oscillating magnetic force, they oscillate up and down creating a measurable change in the light reflected from the surrounding tissue.

Testing the Magnetomotive OCT System

After designing and building the magnetomotive OCT system, we first had to test the system to ensure it met our requirements for  resolution, speed, and magnetic sensitivity. We measured the resolution by imaging small, highly scattering particles and confirmed that we achieved our desired resolution. To test the imaging speed, we imaged human bronchial epithelial cells. These are the cells lining our airways which contain cilia and secrete mucus. The mucus layer acts like a shield preventing the bacteria we breathe in from entering our bloodstream. The cilia beat to propel the mucus (containing all those trapped bacteria) out of our airways and are a vital component of a healthy immune system. Therefore, the ability to image living, beating cilia is helpful to doctors who study respiratory diseases such as Cystic Fibrosis. Our collaborators in the Cystic Fibrosis Center at UNC provided us with a sample of these cells, and we were able to image the beating cilia. This was a very exciting result. Not only did we confirm that our OCT system has a fast imaging speed, but we also discovered that this novel imaging system may be useful for helping to diagnose and research respiratory diseases.

Future Research: Turtles and Beyond

Our imaging speed experiment using epithelial cells demonstrates a vital point in the scientific process: often, by setting out to answer one question, you may open avenues of investigation you had never considered. We demonstrated with this experiment that our OCT system has the best combination of high resolution and high-speed of any OCT system to date. We will next measure the magnetic sensitivity of our system by imaging tissue phantoms, silicone-based samples which mimic the light-scattering properties of biological tissue, containing increasingly small concentrations of magnetic particles. Once we are sure that our system has the desired magnetic sensitivity, we can begin imaging animal tissue. If we are able to locate the magnetic receptors, it would be a huge breakthrough in the study of sea turtle navigation. If we are able to find these receptors, biologists can study them to understand exactly how they are used to sense magnetic fields and how the turtles use that information to navigate. Building this novel imaging system is just one step toward finally understanding sea turtle navigation. In addition, we have also discovered that our technology may have other uses, as our preliminary work with the cilia suggest. We will continue toward our goal of detecting magnetic receptors in sea turtle tissue while also investigating the system’s applications in respiratory disease research.

Peer edited by Allison Lacko and Laetitia Meyrueix.

Follow us on social media and never miss an article:

 

To Dye or Not To Dye

Dyeing hair is a common, but not recent, beauty practice. Hair dyeing (coloring) has been around for thousands of years, using plant-based dyes such as indigo and turmeric before synthetic dyes were invented. I recently wondered “What kind of science goes into modern hair coloringWhat is the process?”  I have had my hair colored before but never even wondered how the coloring occurs. I reached out to my very good friend and cosmetologist, Erin Rausch, and asked her to explain the process.

Like most working professionals, cosmetologists attend school before they begin working with actual clients. While each school has a different curriculum, Erin attended Aveda Institute in Madison, where she spent six months in a classroom learning about anatomy, chemistry, color theory, and the study of the hair and scalp – trichology. In cosmetology, it is exceedingly important to understand the biology of hair, particularly in the case of hair coloring. Like the skin, hair has pores and layers. The hair layers open with heat and close with cold, kind of like when you open an umbrella when it’s sunny and close it when it’s dark. A good cosmetologist understands how chemicals affect and interact with the hair, studies the existing melanin (pigment) of the hair to later replace it with new color. Also, like skin, hair contains different kinds of melanin, and different melanins result in different hair colors: pheomelanin results in hair with a pink to red hue (pheomelanin is also in lips), and eumelanin results in the darkness of the hair: more eumelanin – darker hair, less – lighter hair.

Microscopic image of human hair. Hair has layers, like skin, onions, and Shrek.

Cosmetologists need to consider every aspect of the customers’ hair before continuing to color. First, hair color is sorted into color levels, 1-10; 1 being black, 10 being whitest blonde. Aside from natural hair color, it is important to consider the type (thickness of the hair strand), texture (straight or wavy), density (number of strands of hair per square inch) of the hair, whether the hair has had previous treatment, and the distance from the scalp that you’re treating. The scalp produces heat which causes the color to react a little differently near the scalp than hair away from the scalp. For this reason, it is important to consider the density of the hair. A higher density of hair results in more heat near the scalp, changing how color will interact with the hair near the scalp compared to hair away from the scalp.

Hair levels determined by hair color.

Once all of the variables of the clients’ hair have been evaluated, cosmetologists then formulate how to color. There are several steps in the hair coloring process. First, they always formulate according to the existing natural level of hair color (levels 1-10). Dyeing hair is essentially a melanin exchange where natural melanin is exchanged with a different, synthetic one. Removing natural melanin is done with ammonia or bleach, partnered with peroxide; causing a chemical reaction. There are different strengths of peroxide, and the one used depends on type, texture, density, and final desired hair color. It’s extremely important to be careful with peroxide strength, as certain volumes can cause chemical burns and adverse chemical reactions. A common analogy is the peroxide is like the length of time or heat used to cook spaghetti. If you don’t have enough, your spaghetti isn’t cooked, but if you have too much, your spaghetti is overdone. Too much peroxide will severely damage your hair, like overcooking pasta. Depending on the natural hair color or previous hair treatment, it might take more than one peroxide treatment step to remove melanin.

Color Theory. To neutralize Natural Remaining Pigment, the complimentary color is used. For example, Level 10 hair (lightest blonde) has yellow natural remaining pigment, so violet would neutralize the NRP.

After the peroxide treatment, there is still pigment remaining in the hair, called Natural Remaining Pigment (NRP). It is important to neutralize the NRP, so it doesn’t affect the future desired hair color. NRP is neutralized by adding the opposite/complementary color. If Erin wanted to neutralize level 10 (lightest blonde), she needs to use violet. All of the variables are part of color theory and the treatment depends on look you want to create (I should have paid more attention in art class).

A client’s hair is sectioned as color(dye) is being applied.

Once the natural melanin has been removed and the NRP has been neutralized, it’s time to color the hair! The amount of hair color product needed to color the hair depends on hair type and desired color(s). The bigger the hair section (as can be seen in the image above), the less the color will permeate the hair strands evenly. Thus, more hair product will be needed so the hair will be properly colored, and the color will last a long time.

Erin strongly recommends against at home hair dye kits. While they may seem cost effective, their methods for hair coloring can be damaging to your hair. These kits are made to achieve one color and are only designed for people that have no color on their natural hair. Since people have many different kinds of hair and hair color, there is a large chance the at home dye color you pick will be very different from what you want. The peroxide used in the kit is also a very strong peroxide (much stronger than peroxide used in salons) and because the peroxide in the kit is so strong, the color is much harder to remove or correct later on. Essentially, at home hair dye kits are very damaging to hair.

To see Erin’s portfolio, check out her instagram!

Peer edited by Mikayla Armstrong.

Follow us on social media and never miss an article:

Will dogs save us from allergies?

https://www.flickr.com/photos/tomsaint/16730323546

Picture from: Rennett Stowe

Dog is man’s best friend. Man is dog’s…predictor for allergies?

A recent study showed dogs with owners that suffer from allergies are more likely to suffer from allergies themselves. Researchers also found that dogs that live in urban environments are more likely to have allergies than dogs in rural environments. The same correlation between urban environments and allergies is found in humans. Humans in rural environments come in contact with more species of microbes than their urban counterparts. It is thought that contact with many microbes early in life may protect humans from developing allergies. The same phenomenon is thought to occur in dogs. It appears man and man’s best friend have more in common than originally thought.

Allergies in humans and dogs have been on the rise in the western world. There have been many studies to look at the causes of these allergies in humans, but few have looked into the causes in dogs. Researchers at the University of Helsinki in Finland wanted to change this. We already know that humans who live in urban environments are more likely to have allergies than human who live in rural environments. Hakanen and colleagues wanted to know if the same is true in dogs.

Researchers sent surveys to almost 6000 dog-owners in Finland. The survey asked questions about the dog’s breed, the dog’s current environment (urban v. rural), the dog’s environment at birth, the dog’s allergies, and the owner’s allergies. When analyzing the data, they removed dog breeds known to be genetically prone to allergies, so they could focus on environmental factors. After compiling the data, Hakanen et. al. concluded that dogs who live in urban environments are more likely to have allergies than their rural counterparts. It is important to note, the data are influenced by how much time the dog spends outside and how much contact the dog has with farm animals. Strangely, living in larger human families can also protect dogs from developing allergies. This suggests that we might protect our dogs from allergies; similar to the way they protect us from developing allergies.

https://www.flickr.com/photos/dani0010/537522266

Allergy symptoms in dogs can include itchiness, sneezing, hives, constant licking, itchy ears, and itchy, runny eyes. Picture from: Dani

Researchers cannot be certain the cause for differences in allergies between urban dogs and rural dogs and dogs in smaller vs. larger families, but they do have some theories. In humans, the microbiota, or the microbes that live in our bodies and do not cause illness, are an important factor in allergy development. It is thought that humans who grow up in rural areas come in contact with and are colonized with environmental microbes that protect people from allergies. The microbiota is also thought to be important for development of allergies in dogs. Dogs living in rural environments may come into contact with more environmental microbes that protect them from allergies. Furthermore, dogs in larger families likely come into contact with more species of microbes because each family member harbors a unique microbiota.

Though many of the study’s findings are similar between dogs and humans, one difference between human and dog allergies seems to be the impact of birthplace. A dog’s birthplace is not a predictor for allergies in dogs like it is in humans. Researchers think a dog’s birthplace may be less important because dogs are usually removed from their birth environment fairly early (7-8 weeks), when compared to humans (18yrs).

Hakanen and colleagues were able to identify multiple environmental factors important for predicting if a dog will develop allergies. However, the most striking finding of the study was actually in the dog owners. Dogs with owners that have allergies are more likely to have allergies. Though this is not a new finding, it suggests that the factors important to developing allergies in humans and dogs may be the same. The idea that the same factors could influence allergy development in both dogs and humans is particularly intriguing considering dogs suffer mostly skin and food allergies and few respiratory symptoms. Respiratory symptoms from pollen allergies are among the most common in humans. Furthermore, the immune responses that cause allergic symptoms in dogs and humans are different. This suggests the factors influencing allergy development may be important for all mammals despite differences in their immune systems.

There is still more research to be done to determine the factors that lead to allergies in dogs and humans. However, the studies of Hakanen et. al. and others suggest that if we can determine the factors important for developing allergies in dogs, for which it is easier to gather environmental and health information, we may be able to apply these findings to humans. So in addition to being the best listeners, best cuddlers, and our best friends, dogs may just be our best chance to cure our allergies.

Peer edited by Christina Parker

Follow us on social media and never miss an article:

Getting to the Heart of the Matter: “Fish are friends, not food”

https://www.flickr.com/photos/shany_410/1125438164

Repeat after me: “Fish are friends, not food”

When most people think about “Finding Nemo,” they likely think about Nemo, the adventurous young clownfish who got caught up in a fishy situation (no pun intended) and ended up in a dentist’s fish tank. Or, they might remember Marlin, the overprotective father. However, what about Dory? Though some might characterize Dory as loopy, she was the real hero who saved Marlin and Nemo’s lives and reunited father and son. Who would have thought that the loopy blue tang fish would be the unsung hero?

https://commons.wikimedia.org/wiki/File:Zebrafish_(26436913602).jpg

Zebrafish (Danio rerio), possibly the key to treat/cure heart disease

Just like Nemo, humans have their own fish hero too: the zebrafish. The zebrafish is a tropical freshwater fish that is currently used in many research labs as a powerful model organism for studying various diseases such as heart disease, cancer, diabetes, and gastrointestinal disease. You might be thinking that there is no way a 3-5 cm fish, with fins and no lungs, can model human disease; humans are extremely different from zebrafish. However, zebrafish are much more similar to people than one might initially think. In fact, according to a paper published in Nature, 84% of genes known to be associated with human disease have a zebrafish counterpart. You might also be wondering why not use mice? After all, they’re at least mammals. Good question!

Zebrafish models actually have many advantages over mouse or rat models:

  1. Zebrafish reproduce more frequently (every week) than mice and rats.
  2. Zebrafish can easily be genetically manipulated to study a disease; it takes less time to generate a zebrafish mutant line than a mouse mutant line.

    https://www.flickr.com/photos/nihgov/29229249924

    Picture above shows zebrafish blood vessels labelled in red and lymphatic vessels labelled in green

  3. In zebrafish, important pathways can be easily blocked and examined by simply adding the drug to the water. This allows for more cost effective and faster identification of new drugs and new uses for current drugs.
  4. The zebrafish is see-through; fluorescence markers can be used to “highlight” various cells in tissues and organs. Imagine being able to see individual cells migrate from one location to the next and form an entire heart that begins to beat 24 hours later- in real time. THAT’S AMAZING!

Other advantages of the zebrafish are disease specific. For example, zebrafish are an advantageous model for studying congenital heart disease because they can survive severe cardiac defects that are typically lethal in mice. Therefore, the zebrafish model allows scientists to follow a disease longer than they would be able to in a mouse model. Zebrafish models of heart failure have been found to exhibit similar defects to those found in patients with heart disease. In addition, zebrafish heart models have provided genetic evidence that certain signaling pathways protect humans against heart problems.

https://www.flickr.com/photos/uwiscseagrant/7250836704

Zebrafish organs or tissues can be easily visualized because they are see-through

One of the major reasons why people succumb to heart attacks is because heart cells get damaged and die; heart cells have little to no capability to regenerate (make more of themselves). The zebrafish heart, on the other hand, has the capability to regenerate and replace injured heart tissue after damage. Therefore, scientists are using the zebrafish to figure out what factors or pathways are involved in that process, so they may be able to help the human heart heal itself after being damaged during a heart attack. Heart disease is the leading cause of death in the U.S. and worldwide; so, many lives can be saved with the help of a little striped fish, like Dory.

With that in mind, it’s probably safe to say that fish are friends (and not just food).

 

Peer edited by Breanna Turman.

Follow us on social media and never miss an article:

Fun Facts About Cephalopods

https://www.flickr.com/photos/elevy/19188593431/

Octopus are intelligent cephalopods capable of using tools, opening containers, and even play  Photo by: Elias Levy / Flickr

Class Cephalopoda is home to some of the most intelligent and mysterious critters in the sea. Including species of octopus, squid, cuttlefish and nautilus, cephalopods are a type of mollusk that have have lost their hard outer shells. Cephalopods get their name from the Greek word “kephalópoda” meaning “head-feet”, because their arms encircle their heads. Both squid and cuttlefish are known as ten-armed cephalopods because they have eight short arms and two long tentacles (as opposed to eight-armed cephalopods like octopuses).

You surely recognize the sly octopus and the charismatic cuttlefish, but how much do you really know about this class of invertebrates?

Check out these three fun facts:

Squid and cuttlefish may look similar, but don’t be fooled.

For a quick way to tell the two apart, watch them move underwater. Squid are fast-moving predators, where cuttlefish are slower and move by undulating long fins on the sides of their bodies. If that doesn’t work, check out their eyes: squid have round pupils, where cuttlefish pupils are W-shaped. And perhaps the easiest indicator of all? Squid have sleek, torpedo-shaped bodies, compared to the broader, stout body of the cuttlefish.

https://commons.wikimedia.org/wiki/File:Cuttlefish_komodo_large.jpg

Large cuttlefish (from Komodo National Park), while they look similar to Squids, they actually have unique characteristics

Class Cephalopoda is home to one of the most venomous creatures on earth.

The blue-ringed octopus’ venom is 1,000 times more powerful than cyanide, and this golf-ball sized powerhouse packs enough venom to kill 26 humans within minutes. It produces a potent neurotoxin called tetrodotoxin, a potentially deadly substance also found in pufferfish. The venom is produced by symbiotic bacteria in the animal’s salivary glands and is more toxic than that of any land mammals.

So, what happens if you’re bitten by a blue-ringed octopus? First, the venom blocks nerve signals throughout the body, causing muscle numbness. Ultimately, it will cause muscle paralysis—including the muscles needed for humans to breathe, leading to respiratory arrest. If you ever encounter this blue and yellow beauty, back away in a hurry—its bite is usually painless, so you might not know you’ve been bitten until it’s too late.

Octopuses are smarter than you think.

When we think of animal intelligence, it’s vertebrates like dolphins and chimps that get most of the credit. But make no mistake—the octopus holds its own in a battle of wits. Cephalopods have large, condensed brains that have sections entirely dedicated to learning, a trait that is unique among invertebrates. Octopuses’ brilliant problem-solving abilities have been documented time and time again; for example, the infamous Inky the Octopus who slipped through a gap in its tank in a New Zealand aquarium and slid down a 164-foot-long drainpipe into Hawke’s Bay. There’s also evidence octopuses have personalities, and react differently based on how shy, active or emotional they are.

There you have it! Now, go out and impress your friends with your knowledge of these quirky and intriguing invertebrates!

Follow us on social media and never miss an article:

Stop Insulting Anglerfish Sex

http://www.photolib.noaa.gov/htmls/expl5923.htm

A deep sea anglerfish called a goosefish and is a member of the Lophiidae family – Sladenia remiger.  Image Credit: NOAA Okeanos Explorer Program, INDEX-SATAL 2010

You may have seen the anglerfish sex video floating around the Internet recently, with titles like “The worst sex in the world is anglerfish sex, and now there’s finally video.” While the video is worth a watch, I think most behavioral ecologist would beg to differ with the main assertion: there’s a lot of bad sex in the animal kingdom.

Why is anglerfish sex supposedly so terrible? A male anglerfish bites a females when he finds her, and then hangs onto her for the rest of his life, essentially turning into a living sac of sperm. But hey, at least he’s alive. In contrast, some species of male widow spiders somersault into the mouths of females as they mate, impaling themselves on their mates’ fangs. It sounds like an evolutionary enigma–why would an organism ever willingly sacrifice itself?–but turns out that that self-sacrifice can increase a male’s chances of fathering the female’s offspring.

https://commons.wikimedia.org/wiki/File:Traumatic_insemination_1_edit1.jpg

The female bed bug (the larger of the two) is traumatically inseminated by the male (bottom) through her abdomen.

Traumatic insemination” is another great example of not-so-great sex. In this case, bed bug females are the ones getting royally screwed, because traumatic insemination is a nice way of saying males stabbing females through the abdomen with their penises. The sperm then travels through the female’s hemolymph (the insect equivalent of blood), until reaching the ovaries and fertilizing the eggs. Males mate with all available females, because the last male to mate with any given female has the best chance of fathering her offspring. However, females who are subjected to these multiple matings pay a high cost: they have shortened lives and reduced reproductive output, because they have to allocate energy to healing the wounds and dealing with any resulting infections.

People often assume that two organisms mating with one another have the same “goals.” After all, both males and females are presumably invested in having as many healthy offspring as possible. But this is only true up to a certain point. Female widow spiders don’t need males to remain alive after mating, and in fact gain an advantage from eating the male (a ready source of nutrients that will help her with her next clutch!). In contrast, male widow spiders obviously benefit from not being eaten, and instead living to mate another day. Similarly, mating multiple times via traumatic insemination is costly to female bed bugs, who only need enough sperm to fertilize their eggs, while male bedbugs benefit from mating as many times as possible.

These are examples of what biologists call sexual conflict. While the source of conflict is obvious in the widow spiders’ and bed bugs’ cases, sexual conflict occurs anytime male and female genetic interests don’t align. In fact, the only time there is absolutely no potential for conflict is when males and females have exactly the same lifetime reproduction, so that each is equally invested in all of their shared offspring, with no opportunities for having offspring with other partners. In contrast, conflict can arise whenever one sex has the opportunity to improve their chances of having more, or better, offspring. This can happen in many different ways, such as: eating your partner, mating multiple times with the same partner, or even mating with multiple partners.

As a result, sexual conflict isn’t likely in anglerfish, at least those species which only have one mate for their entire lives. Although there are genera of anglerfish where females can have up to 8 males hanging off of her! So there’s potential for sexual conflict there, since the males will presumably compete to father her offspring and could do so in ways that are harmful to the female. However, anglerfish are incredibly hard to study because they generally occur in the deep sea. Frankly, male anglerfish have way more going for them than you might’ve ever thought–keep that in mind next time someone’s making fun of them.

 

Peer edited by Karen Setty.

Follow us on social media and never miss an article:

Honey Bees: Conservation Icon or Environmental Problem?

Bzzzzztt! Oh, sorry. That was just the sound of another honey bee dying. Seriously though, honey bee populations are crashing all over the world – we’ve lost nearly 60% of honey bee colonies since the 1970s. But there’s good news! Honey bees might be on the verge of making a comeback. Numerous conservation agencies and local businesses are making hard attempts to increase the number of honey bee colonies in all sorts of places – Barack Obama even launched a special task force in 2014! So, with all these good bee-vibes, why did one prominent bee researcher write a perspective article in Science poo-pooing the spread of honey bees as conservation icon? Let’s break it down.

https://www.flickr.com/photos/usgsbiml/34240025053/in/photolist-eenRKb-krfu9P-gkdW7q-eecLmq-ee75bt-ghnAju-gkdBS7-eecL6L-gkdV6Y-ghnDb1-o3mrPi-nBR2iN-nLb438-o5qWJe-UTSk1U-UTS5DN-U7KeYY-UaF5xx-V9MmSw

Apis mellifera, the European honey bee and maybe your best friend?

Get to the point. What’s the problem?

Sure, right away. As mentioned above, honey bees are vanishing at an alarming rate. Much of this phenomenon is associated with something called Colony Collapse Disorder (CCD). One day, all the bees are happy and making honey, then the next the workers have suddenly vanished and abandoned their queen and hive. In a frustrating turn of events, nobody knows quite what is causing CCD. Many experts believe CCD is attributed to a variety of factors: increased use of pesticides, a virus-harboring parasite, poor nutrition, climate change, and even cell phones (OK, you caught me: that last one isn’t widely supported). At this point, about 40-50% of established hives don’t survive to the next year – a significant change from decades past. If this worrisome trend continues, honey bee populations could plummet with a cascade of consequences.

Do honey bees really matter, though? I hardly eat honey.

Great rhetorical question (and also, what’s wrong with you?)! Honey bees are indispensable to our nation’s agriculture. While several staples of American agriculture such as wheat and corn are wind-pollinated, many others need help from other organisms to spread their pollen from one flower to the next. In fact, honey bees are essential for the pollination and production of a huge variety of crops such as apples, cantaloupes, almonds, and avocados. Honey bee-pollinated foods contribute more than 15 billion dollars to the US agricultural economy and their continued decline could increase consumer costs of these foods to ten times their current price.  

Honey bee products also make up their own economy. Honey produced by American beekeepers is a 300-million-dollar industry, while hive by-products such as beeswax, have niche markets as well (who here hasn’t heard of Burt’s Bees?).

https://www.pexels.com/photo/bee-on-flower-811691/

Honeybees play an essential role in the reproductive cycle for many flowers and plants that produce our food

The benefits of managed hives aren’t limited to large scale commercial farmers or beekeepers. Many people report that keeping bees improves the health and vibrancy of their own gardens. Consuming locally-produced honey might (emphasis on might) also help with allergies, attuning your body to the pollens it’ll be lambasted with in spring and fall. Local hives also present a fantastic opportunity to teach lessons about biology to students of any age – did you know honey bees are actually the only domesticated superorganism? (Don’t know what a superorganism, is? Look here. See, learning opportunity!)

Ok, so what’s up with this anti-honeybee article? Is the guy just a jerk?

Dr. Jonas Geldmann is actually a renowned conservation researcher at the University of Cambridge, and probably a great guy! His recent perspectives article in Science highlights a growing concern among environmental conservationists. While honey bees are fascinating and powerful machines of agriculture, high densities of managed hives also present an environmental quandary. A growing body of research suggests that domesticated honey bees, with up to 60,000 bees in a hive, may be harmful to their wild, native neighbors. Honey bee hives require huge amounts of nectar and pollen to stay healthy and produce honey, potentially placing them in direct competition with native pollinations for food. Additionally, honey bee hives can become incubators for parasites and pathogens that can be directly transmitted to other bee and insect species, impacting their health and fertility. While the jury’s still out, the accumulating evidence suggests that introducing honey bee hives can measurably reduce local populations of native bee species, which can have negative impacts on the local environment.

https://commons.wikimedia.org/wiki/File:Rhododendron_canescens_43zz.jpg

Piedmont azalea (Rhododendron canescens) is native to North Carolina

Native pollinators, which include thousands of distinct bee species as well as butterflies, moths, bats, flies, ants, and birds, are also capable of performing a significant portion of the pollination needs of both agricultural and non-agricultural plants. In many cases, native plant species have uniquely adapted to be efficiently pollinated by their native pollinators. A beautiful example of this is the flowering azaleas, which bloom in the early spring. Unlike many flowering plants, azalea pollen is hidden deep inside their flowers – where only native bees know to look.­­­­­ North Carolina is home to several native species of deciduous azaleas, none of which can be pollinated by domesticated honey bees. Similarly, crop plants such as squash, alfalfa, and blueberries all have native bee species that are significantly more efficient at fulfilling their pollination needs than their domesticated relatives.

Unfortunately, many native pollinators are experiencing serious population declines similar to the honey bee. For evidence, we only have to look back at the agriculture industry. In the past, native pollinators were the sole source of pollination for many of the food crops that are now completely reliant on managed honey bee hives. While the honey bee has done a fantastic job of keeping these foods from vanishing off our shelves, it won’t be able to maintain the diversity of our nations flora alone. It is imperative that we keep our native pollinators in mind when discussing conservation efforts and adopt policies that promote the health and wellbeing of both native and domesticated bee species.

What can you do?

Fear not, for all is far from lost! Helping out is simple! Native and domesticated species of bee both struggle with some of the same issues: a lack of resources (nectar and pollen) and exposure to pesticides. When buying plants for your own garden, look for native species that produce plenty of nectar and pollen (also known as bee-food!) and ensure that they are pesticide free. If you’re feeling overwhelmed, contact your local beekeepers association or honey bee researcher – they will often have resources available such as this one from the North Carolina Cooperative Extension. While tending your garden, try to avoid using pesticides and only use natural, bee-friendly ones if you must – many local garden supply stores will carry such products. There are also ways to help if you aren’t an avid gardener! In an ideal world, we’d all buy locally-sourced, pesticide-free produce (which you can do! Talk to growers at your local farmers market about their practices), but that process can be a bit daunting. While imperfect, USDA certified organic foods are grown using naturally-sourced pesticides (like raw copper or sulphur), which likely aren’t as toxic to local pollinators. By sticking to these practices, anyone can promote the health of native pollinators and honey bees, alike.

Peer edited by Erica Wood.

Follow us on social media and never miss an article:

The Terminator of the Genome

https://www.flickr.com/photos/bagogames/19869372178

The real Terminator

“Listen. Understand. The Terminator is out there. It can’t be reasoned with, it can’t be bargained with… it doesn’t feel pity or remorse or fear…and it will absolutely not stop. Ever. Until you are dead.” In the movie “The Terminator”, the Terminator’s one job was to kill a woman whose son will later hurt his cyborg people. You may wonder what the Terminator has to do with molecular biology but it’s actually quite relevant. We have a ‘terminator’ in our body called p53; its job is to kill rogue cells and prevent cancer from spreading through our bodies at all costs.

p53 works as a gatekeeper in the cells of our body. Just like how gates prevent criminals from getting out when they’re not supposed to, our cells have gates and security to prevent rogue cells, like cancerous cells, from squeezing past checkpoints that make sure cells are normal and healthy. Cells grow, mature and reach a point where they need to divide to make new cells. Each of these steps have checkpoints that make sure the cells are normal and healthy so that the new cells aren’t abnormal or cancerous. Without this security, cancer cells would be running rampant in our bodies. Many cancers are caused by a loss of security in the cell, allowing cancer cells to grow and divide without being stopped at these checkpoints. p53 is one of these gatekeepers. Its function is crucial for cell regulation, cell death and checking cells to make sure they’re not abnormal and cancerous.

When a cell grows and divides, it stops at certain checkpoints in that process to make sure nothing is abnormal and that it is a healthy cell. p53 acts at these checkpoints in the cell to inspect and ensure that the cell isn’t mutated or messed up in any way. If the cell passes inspection, then it moves along and keeps growing and then exits the cycle of growing and dividing. If p53 catches a rogue cell trying to sneak past a checkpoint with mutated DNA or too many chromosomes, it calls in a whole arsenal of molecules called caspases that kill the cell through a process called apoptosis or prevent the cell from making new cells.

Gatekeeper molecules are very important to the cell because they prevent mutated cells from growing and making more mutated cells, eventually leading to cancer or neurodegenetive disease. p53 is activated by cell stress, like external heat or toxins. Stress signals that there is something wrong with the cell division process and that there needs to be more stringent inspection of cells to determine the cause of cell stress and to get rid of it. The problem becomes when gatekeeper molecules themselves are mutated like how border guards can be corrupted or bribed. When p53 in a cell is corrupted, nothing else is checking the cell’s genome to see if it is mutated. These cells get a free pass to divide, thrive and build up in places they shouldn’t be, which is what causes cancer.

 https://commons.wikimedia.org/wiki/File:P53.png

p53 (blue) interacting with DNA (orange)

p53 is mutated in over 50% of cancers like ovarian cancer, breast cancer and colorectal cancer. When working properly, p53 is a tumor suppressor but when it is mutated, is becomes an oncoprotein, a protein that promotes cancer. Two copies of p53 or two gatekeepers are needed in each cell in order for p53 to inspect and shut down rogue cells properly. However, in cancer, one of these copies of p53 is mutated and the other copy is unable to keep up with all the inspections that need to be done. In aggressive cancers, the remaining copy of p53 can become mutated into an oncoprotein and help rogue cells grow, divide and spread to other parts of the body.  

There are various ways that the body tries to prevent mutant p53 from enabling cancer to grow. One of these is through the protein Mdm2 which targets p53 for degradation. When the cell is happy and under low stress, p53 does not need to cause cell death. However, if p53 is mutated it will try to kill the cell. At this point, Mdm2 destroys p53 because it can see that p53 isn’t working properly. Mdm2 is responsive to p53. If p53 levels go up, Mdm2 levels go up as well so that the cell is working properly and is regulated. However, in cancer, Mdm2 can be shut down by other mechanisms so that it can’t shut down p53.

At UNC, Yanping Zhang’s lab studies the Mdm2-p53 pathway. In particular, they study what happens when Mdm2 is mutated and can’t degrade abnormal p53. Thus far, they have found that under conditions of low stress, Mdm2 can be mutated and not have any adverse effects on the cell. However, mice that do not have any Mdm2 were not viable because, left unregulated, p53 constantly killed the cells no matter if they were abnormal or not.

p53 is an amazing protein that works hard to terminate all the abnormal cells in our body. Hopefully, through more study, we can find ways to prevent the mis-regulation of p53 and thus help treat cancers due to p53 mutations.

Peer edited by Samual Honeycutt and Mimi Huang.

Follow us on social media and never miss an article: