How Cheese Helped Us Understand Microbial Interactions

In almost every environment on earth, such as soil, human skin and gut, there lives a whole community of microbes—sometimes up to hundreds of species. It may seem like they all flourish in peace. But just like you may have friendly or hostile interactions with your neighbors, the different bacterial species interact in various ways. They may cooperate, compete or, sometimes, even kill each other. The interaction is complicated, and scientists have struggled to understand the nature of these microbiome interactions. How do microbiomes assemble and maintain stability? How do the interactions among different species affect gene expression?

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Combatting Gun Violence with Synthetic Biology

Imagine you are a high school student living in a community devastated by gun violence and death. In the U.S., this could be one of many communities, but it happens to be Baltimore which had 301 deaths due to gun violence in 2017 (with a per capita rate well above other large cities). Then imagine you were part of an organization within that community that helped you, along with other students, gain knowledge and skills to come up with a viable solution to the problem using synthetic biology.

Baltimore Bio-Crew at the 2018 iGEM Giant Jamboree

This is exactly how the Baltimore Bio-Crew came up with their iGEM project, Coagulance Rx. The Baltimore Bio-Crew decided to tackle this community issue head-on. One team member, Mercedes Ferandes, reflected, “Living in Baltimore City, I have not only witnessed gun violence in front of me, but have had family members and friends die from it. I wanted to try to decrease the amount of deaths by gun violence using iGEM.”

After some research, they discovered that many of the gun deaths were due to blood loss and could have been prevented. The impoverished neighborhoods where this violence occurs lack the resources to provide timely emergency medical treatment. Many of these deaths can be attributed to delayed arrival of emergency response teams—wait times for an ambulance can be over an hour.

Although there were several contributing factors beyond their control, the team wanted to address this problem by focusing on blood clotting and how it could be helpful as a quick temporary treatment for open wounds. This solution could offer a reliable, cost efficient way to save lives by slowing or stopping blood loss until a victim could get medical attention. The team decided to pursue the use of snake venom after coming across some previous iGEM projects that had used it for clotting. Team member Henry Ryles pointed out that the need for snake venom powerful enough to clot blood quickly led them to choose the venom of the Russell’s Viper
(Daboia russelii).

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A Roadmap for PROTAC Development

PROTACs or Proteolysis-Targeting Chimeras are an emerging tool in protein degradation studies, potentially suited to any need involving the removal of a specific protein. These small-molecule chimeras are exciting due to: 1) their target specificity; and 2) their ability to enable target destruction versus target inhibition.

Destruction/Inhibition: Is There a Difference?
An analogy that microbiologists (and wrestlers or anyone that has ever spent time in a locker room shower) would understand, is fungicidal versus fungistatic compounds. A fungicidal compound kills fungus. A fungistatic compound just slows the fungus down a bit.

A small-molecule inhibitor attaches to its target protein, but for how long? What inhibitor testing must be done to determine how long the inhibition lasts?

On the other hand, a small-molecule agent that causes protein degradation first targets the protein of interest, then attaches ubiquitin to that target. Once a protein is marked with ubiquitin, it’s a dead man. E3 ligase must be involved, but if the ubiquitin is added by E3, the end is near. Next stop, Hades.

This ubiquitinated protein is headed to the proteasome and proteins that go there don’t come back. Ubiquitination was called the ‘molecular kiss of death’ when this discovery was awarded the Nobel prize in Chemistry in 2004.

PROTAC components: target protein ligand, E3 ligase and linker.

About PROTACs
PROTACs are degrader molecules composed of three parts: 1) a ligand that is specific for the target protein; 2) a ligand for E3 ligase; and 3) a linker molecule that connects the two ligands. The E3 ligase is one of three enzymes that can add ubiquitin to a cellular component, but only ubiquitins added by the E3 ligase cause targeting to the proteasome (Zoppi et al.).

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Understanding Mechanisms of Pesticide Resistance to Thiamethoxam in the Cotton Aphid

A. gossypii on cotton leaf. Image credit: Clemson University - USDA Cooperative Extension Slide Series, , United States [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons
A. gossypii on cotton leaf. Image credit: Clemson University – USDA Cooperative Extension Slide Series, , United States [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons

The extensive and repetitive use of neonicotinoids has led to the development of resistance in several insect species including, the cotton aphid, A. gossypii. A. gossypii is a widely distributed pest that affects watermelons, cucumbers, pumpkin, cotton, and citrus crops, among others, making it one of the most economically important agricultural pests known. Thiamethoxam is a neonicotinoid insecticide that irreversibly binds to the nicotinic acetylcholine receptors (nAChRs) of cells in the nervous system and interferes with the transmission of nerve impulses in insects (1).

To further understand the mechanisms of resistence to thiamethoxam and other neonicotinoids, Wu et al. recently investigated (2) expression changes in the transcripts of P450 in thiamethoxam-susceptible and thiamethoxam-resistant cotton aphid strains. Nine P450 genes were significantly overexpressed in the resistant strain (especially CYP6CY14). The involvement of overexpressed P450s was examined through RNA interference (RNAi) introduced via artificial diet and dsRNA feeding.

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“We’re From NASA”: How Citizen Science Helped Find Ultima Thule

The science world is a-twitter with excitement lately, following the recent arrival of the New Horizons spacecraft at 2014 MU69, dubbed “Ultima Thule” by popular vote. The name means “beyond the borders of the known world”, signifying Ultima Thule’s status as the most distant object ever visited by Earthly spacecraft. Ultima Thule is a dark reddish rock in the Kuiper belt, a contact binary formed by two smaller rocks coming together in what was presumably a gentle fashion.

Do you wanna build a snowman? Credit: NASA/Johns Hopkins University Applied Physics Laboratory/Southwest Research Institute

Reaching this space snowman 6.5 billion kilometers away from Earth took brains, dedication, ingenuity and the help of an unnamed Argentinian man and his daughter.

To successfully intercept Ultima Thule, the New Horizons mission team needed to answer some questions, such as “What trajectory is Ultima Thule on?” and “Is there any space debris around Ultima Thule that will destroy our spacecraft?” Being so small (~30km diameter at its widest point), observing Ultima Thule directly from this far away would be too difficult, so the team relied on data gathered during stellar occultations, i.e., when Ultima Thule passed in front of a star.

One of these occultations occurred on July 17, 2017, in the Patagonia region of Argentina. The team had already struck out twice in trying to observe Ultima Thule passing over a star: once in South Africa, and again using the airborne telescope SOFIA over the Pacific Ocean, so tension was already running high.

On this particular night, it happened to be very windy where the observation team was, which is bad news when you’re trying to hold steady focus on a tiny object that’s really far away. The team found themselves needing help to shield the telescopes they had brought with them from wind vibrations, and get the data from the star “without it jiggling around all over the place”, as planetary scientist Anne Verbiscer puts it.

Where does one find volunteers for an astronomical observation? Well, apparently even in Argentina NASA is known and loved, and help can be found just by walking into the community. “If you just started out with ‘We’re from NASA,’ people started coming out of the woodwork,” said Dr. Verbiscer. And that is how one Argentinian man and his daughter ended up spending their evening blocking the wind from a telescope using a truck, a tarp and some plywood, allowing the NASA folks to collect the data they needed to send New Horizons to Ultima Thule.

Want to learn more about the search for Ultima Thule? Check out the episode of NOVA that inspired this blog!

2019: International Year of the Periodic Table

Periodic table of the elements

From the inside covers of elementary science textbooks to the walls of chemistry labs all around the world, the periodic table is one of the most pivotal and enduring tools of modern science. To honor the 150th anniversary of its discovery, the United Nations General Assembly and UNESCO have declared 2019 to be the International Year of the Periodic Table of Chemical Elements.

As with all scientific progress, Dmitri Mendeleev’s periodic table was the result of decades—centuries, even—of research performed by scientists all over the world. Aristotle first theorized the existence of basic building blocks of matter over 2,500 years ago, which later were believed to be earth, air, fire and water. Alchemist Hennig Brand is credited with discovering phosphorus in the late 17th century, sparking chemists to begin pursuing these basic atomic elements.

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Dane County High School Students Attend Stem Cell Conference at Wisconsin Institutes for Discovery

Dane County highschool students in attendance at the stem cell conference.


Embryonic stem cells have the extraordinary ability to divide without limit yet maintain the potential to make all types of cells found in the human body.  This holds tremendous implications for the worlds of drug discovery and testing, cell production, and tissue transplantation medicine.

Benjamin


Overall, I’m really glad I decided to go to the talk.  I got to learn a lot about stem cells, how they are used in different parts of the body, and some of the difficulties with using stem cells.  It was definitely way more enjoyable than anything else I was planning on doing during that time.  If there are more opportunities like this that come up, I would definitely try to go to them. 

Thomas

Celebrating the 20th anniversary of Dr. James Thomson’s breakthrough work with induced pluripotent stem cells, the Wisconsin Institute for Discovery (WID) hosted a panel of University of Wisconsin stem cell scientists to discuss the future of their research on November 13th.  Entitled “Stem Cell Science: The Next 20 Years” and designed for the general public, the audience heard from Drs. Lynn Allen Hoffman, David Gamm and David Vereide, who talked about applying stem cell research to develop clinical applications for skin grafting, vision restoration and regenerative biology, respectively.

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Light: A Happy Pill for Dark Days?

Light: A Happy Pill for Dark Days?

Have you ever had a day where you feel exceptionally good? As in take on the world kind of good? You feel so much better than the previous couple of days that you stop to wonder why.

Then it dawns on you.

The sun is out. It’s been cloudy for the past week but now—SUNSHINE.

You go out to lunch or for a walk just to take in those rays. Sure, it feels warmer than your darkened office space, but it’s the light rather than warmth that’s making a difference.

You purposely don’t wear sunglasses and it feels like the light is coming in through your eyes and massaging that part of your brain that is your happy zone. Are you imagining it or is the sun really affecting how you feel?

In a study reported in the September 2018 issue of Cell we learn that this is not a figment of your or my imagination (1). There is, in fact, a type of retinal cell that transports sunlight directly to the part of our brains that affects mood.

Eyes and the Body’s Master Clock

Circadian rhythms are innate time-keeping functions found in all multicellular organisms. This subject of the 2017 Nobel prize in Physiology or Medicine, circadian rhythms are fueled by daily light-dark cycles and are critical to the function of neurologic, immune, musculoskeletal and cardiac tissues (2). Nearly every mammalian cell is affected by circadian rhythms.

The human body has a circadian master clock, the suprachiasmatic nucleus or SCN. The SCN is a highly innervated tissue located in the hypothalamus (see image). It is connected directly to the retina by the optic nerve, and thus is influenced by external light and dark.

Light enters eyes and is transmitted to SCN and PHb.
Light enters the eyes and affects the SCN (physiologic effects), and as discussed in recent research, Fernandez et al. here, the perihabenular nucleus (behavioral effects). (Image in public domain.)

The retina of the eye is the light gathering instrument for this organ. Historically, it’s been understood that the retina is composed of two cell types, rods and cones, that function in transmitting light and images to the optic nerve, which sends those signals to the brain.

Drawing of the retina with rods and cones, some nervous tissues.
Some parts of the retina. Light enters the eye (from left) and passes through to the rods and cones. Here a chemical change converts the light to nerve signals. Image based on drawing by Ramón y Cajal, 1911 and licensed under Wikimedia commons.

Studies by Hattar et al. in the early 2000s identified that another cell found in the retina, the melanopsin-containing intrinsically photoactive retinal ganglion cells (ipRGCs) as the transmitter of circadian light signals (3). Through this direct connection to the SCN, the circadian master clock, the ipRGCs can influence a wide range of light-dependent functions independent of image processing (4).

Now Fernandez et al. have identified multiple types of ipRGCs. They showed that ipRGCs that mediate the effects of light on learning work via the SCN, while the pathway for light influencing emotions is different.

They discovered a new target of ipRGC cells, the perihabenular nucleus (PHb). The PHb is a newly recognized thalamic region of the brain. The authors showed that the connection between light and mood is regulated by ipRGCs through the PHb versus the SCN. They show that the PHb is integrated into other mood-regulating centers of the thalamic region.

You can see the details of their studies here.

In Conclusion

Daylight, and lack thereof, does affect both our mood and our ability to learn. In this 2018 report, we have learned that the pathways for these effects are distinct, and gain an understanding of a new thalamic region by which the light and mood actions occur. This information could influence development of better drugs and/or therapies for major depressive disorders.

For those of us with seasonal affective disorder, the evidence is undeniable—lack of light can cause issues, from sleep-wake problems, to mood and learning issues.

And while we can’t create sunshine, a special lamp or light box may help to gain some full spectrum light. To learn more about how to choose such a lamp and when to use it, see this Mayo clinic article for details.

References

  1. Fernandez, D.C. et al. (2018) Light affects mood and learning through distinct retinal pathways. Cell 175, 71–84.
  2. Ledford, H. and Callaway, E. (2017) Circadian clock scoops Nobel prize. Nature 550, 18.
  3. Hattar, S. et al. (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295, 1065–70.
  4. Hattar, S. et al. (2003) Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424(6944)76–81.

4 Things We Recently Learned About Cats

We know a lot about cats. We know that they’re adorable, they make us happy and they can survive a fall from a 32-story building. But apparently, there’s still a lot we don’t know about them. Here are four things we only recently discovered about cats.

1. Sharp, tiny “papillae” on cat tongues help deep-clean their fur.

Cats spend much of their time licking themselves. On the surface of their tongue are hundreds of tiny claw-shaped spines called papillae, each the size of half a grain of rice. Recently, a study published in PNAS revealed the purpose of these structures. The authors found that the tips of the papillae create a U-shaped cavity (imagine a coffee straw cut in half). The cavity holds saliva and helps move it down through the fur to the cat’s skin, allowing deeper cleaning. “Why should I care,” you ask? With these results, the authors created a brush that mimics a cat’s tongue. It tugged less and was easier to clean than a normal brush. The new design could be used to distribute cleaning solutions into carpets. Or, remove allergens from cat fur.

2. Feral cats aren’t great at controlling city rat population.

Many people assume that feral cats hunt and kill rats, helping control city rat population. However, a recent study showed that they’re not doing a great job. The researchers set up cameras around a rat colony in New York City and recorded the behaviors of feral cats that came near. A lucky graduate student watched all 306 videos and tallied cat behaviors such as walking, stalking and chasing. Over 79 days, only three times did a cat actively hunt a rat; and of the two cases in which the hunt was a success, the rats were relatively small in size. The presence of the cats did, however, cause the rats to hide more. Bottom line, let’s not release cats to control rat population.

3. Male cats tend to be left-pawed, and females right-pawed.

Just like humans can be left- or right-handed, cats also prefer using one of their paws over the other. The scientific term for this is called laterality, and it has been examined in many animals including rats, frogs, primates and whales. In this recent study, the paw preference of 44 pet cats were examined in their own homes. They found that most cats showed laterality when reaching for food (73%), stepping down stairs (70%) or stepping over their litter box (66%). While 90% of humans are right-handed, laterality in cats is much more equal—roughly half are left-biased and half right-biased. Surprisingly, the researchers also discovered that male cats are much more likely to prefer their left paw, while females prefer their right paw. The reason is unclear, but it may hint at the underlying differences of the male and female brains.

4. Cats domesticated themselves over thousands of years without much genetic change.

Humans can’t tell cats what to do—they do what they want, when they want. If you’ve ever had a cat, you know it’s true. In fact, this statement also applies to how they were domesticated. In a comprehensive study, researchers examined ancient DNA from more than 200 cats spanning the last 9,000 years and found that the modern domestic cat comes from two main lineages: one from southeast Asian and the other from Egypt. Cats likely began hanging out with humans when our ancestors began farming. With an abundance of rodents that fed on crops, cats voluntarily stayed close and slowly domesticated on their own. The genetic makeup of domesticated cats hasn’t changed much over thousands of years, except the appearance of striped or blotched tabby coat markings. And why would they change? They’re perfect just the way they are.

Over 50 million Died in the Pandemic of 1918-A Century Later We are still Searching for a Universal Flu Vaccine

One hundred years ago, the world was taking its first deep breaths as it celebrated the end of World War I. The Armistice of Compiègne, was signed on November 11,1918, officially ending the four-year long conflict, which claimed the lives of more than 8 million soldiers (1). What the world didn’t yet realize was that they had been battling a far deadlier enemy in the hospitals and at home than any army the soldiers faced on the fields of war.

During the last year of the war, a deadly influenza virus rampaged around the globe leaving between 50 and 100 million dead in its wake.

Influenza Ward, France 1918. 


The boys were coming in with colds and a headache and they were dead within two or three days. Great big handsome fellows, healthy men, just came in and died. There was no rejoicing in Lille the night of the Armistice.
Sister Catherine Macfie from her post at casualty clearing station no. 11 at St André near Lille, France (2).

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