Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Biology Page 1 of 21

Meet New Blogger Anna Gotskind: Science and Gilmore Girls

Hello! My name is Anna Gotskind. I’m a first year originally from Chicago. I plan to double major in biochemistry and environmental science and policy with a certificate in innovation and entrepreneurship (I know it’s a mouthful).

I fell in love with science in seventh grade, inspired by a great teacher named Mark A. Klein. He wore a different tie every day of the year, had tarantulas as pets and frequently refused to say anything but “9” until 9:00 am. He also taught me to appreciate research and discovery, guiding me as I conducted my first independent experiment on the caffeine content in tea which helped me win my middle school science fair.

One of my other role models is Rory Gilmore from the T.V. show Gilmore Girls (yes, I am aware that she is a fictional character). Inspired by watching her write for the Yale Daily News I decided to join the Duke Chronicle when I got to campus. I quickly learned that I loved writing for a publication but more specifically that I loved writing about science. It was incredibly exciting for me to read a study, interview the researchers who conducted it and then translate the information into a story that was understandable to the public. Beyond this, it was also incredible to be exposed to groundbreaking research that had real-world impacts. Essentially, it made me feel like a “Big Girl” and when you’re only 5’0” tall, sometimes that’s necessary.

Rory Gilmore

My love for science does not end in the classroom. My greatest passion is travel and I’ve been fortunate enough to travel around the world with my family exploring some of nature’s greatest wonders. We’ve hiked Bryce Canyon in Utah, Ali San in Taiwan and Masada in Isreal. In December 2018 we ventured to the Galapagos, which as an aspiring environmentalist was an incredible experience. We go to see tortoises, iguanas, penguins, sharks and sea lions mere feet away. Right now I’m working with Duke Professor Stuart Pimm on a Big Cats Conservation Initiative sponsored by SavingSpecies, analyzing camera trap data of species in Sumatra, Brazil, and Ecuador. So who knows, I may be off there next. For more pictures check out my Instagram page @annagotskind (shameless plug).

A Parrot my little brother Avi photographed in the Amazon Rainforest in Ecuador

I’m very excited to continue exploring and writing about the research being done on Duke’s campus!

By Anna Gotskind

The Importance of Moms

Emily Bray, Ph.D., might have the best job ever. Since earning her bachelor’s at Duke in 2012, she has been researching cognitive development in puppies, which basically means she’s spent the last seven years playing with dogs. If that’s not success, I don’t know what is.

Last Friday marked the 10th birthday of Duke’s Canine Cognition Center, and the 210th birthday of Charles Darwin. To celebrate, Brian Hare, Ph.D., invited former student Bray back to campus to share her latest research with a new generation of Duke undergraduates. The room was riveted — both by her compelling findings and by the darling photos of labs and golden retrievers that accompanied each slide.

Dr. Emily Bray shows photos of her study participants

During her Ph.D. program at the University of Pennsylvania, Bray worked with Robert Seyfarth, Dorothy Cheney, and James Serpell to investigate the effects of mothering on puppy development. For her dissertation, she studied a population of dog moms and their puppies at The Seeing Eye, Inc. The Seeing Eye is one of the oldest and largest guide dog schools in the U.S. They have been successfully raising and training service dogs for the blind since 1929, but like most things, it is still an imperfect science. Approximately half of the puppies bred at The Seeing Eye fail out of program. A dog that completes service training at The Seeing Eye represents two years of intensive training and care, and investing so much time and money into a dog that might eventually fail is problematic. Being able to predict the outcomes of puppies would save a lot of wasted time and energy, and Emily Bray has been doing just this.

What makes a good dog mom? (Photo from Dirk Vorderstraße, from Wikimedia Commons)

Through her work at The Seeing Eye, Bray found that, similar to humans, dogs have several types of mothering styles. She discovered that dog moms tend to fall somewhere on the spectrum from low to high maternal involvement. Some of the moms were very involved with their puppies, and seldom left their side. These hovering moms had high levels of cortisol, and became quite stressed when separated briefly from a puppy. They coddled their children, and often nursed from a laying down position, doing everything they could to make life easy for their babies. On the other side of the spectrum, Bray also observed moms that displayed much more relaxed mothering. They often took personal time, and let their puppies fend for themselves. They were more likely to nurse while sitting or standing up, which made their children work harder to feed. They were less stressed when separated from a puppy, and also just had generally lower levels of cortisol. Sound like bad parenting? Believe it or not, this tough love actually resulted in more successful puppies.

Duke’s very own assistance dogs in training!

As the puppies matured, Bray conducted a series of cognitive and temperament tests to determine if maternal style was associated with a certain way of thinking in the puppies. Turns out, dogs who experienced high maternal care actually performed much worse on the tests than dogs who were shown tough love when they were young. At The Seeing Eye graduation, it was also determined that high maternal care and ventral nursing was associated with failure. Puppies that were over-mothered were more likely to fail as service dogs.

Her theory is that tough love raises more resilient puppies. When mom is always around, the puppies don’t get the chance to experience small stressors and learn how to deal with challenge. The more relaxed moms actually did their kids a favor by not being so overbearing, and allowed for much more independent development.

Bray is now doing post-doctoral research at the University of Arizona, where she is working with Canine Companions for Independence (CCI) to determine if maternal style has similar effects on the outcomes of dogs that will be trained to assist people with a wide range of disabilities. She is also now doing cognition and temperament tests on moms pre-pregnancy to determine if maternal behavior can be predicted before the dogs have puppies. Knowing this could be a game changer, as this information could be used for selective breeding of better moms.

Me snuggling Ashton, one of the Puppy Kindergarten dogs

If you got the chance to hang out with puppies Ashton, Aiden, or Dune last semester, you have an idea of how awesome Bray’s day-to-day work is. These pups were bred at CCI, and sent to Duke to be enrolled in Duke Puppy Kindergarten, a new program on campus run through Duke’s Canine Cognition Center. Which of these three will make it to graduation? I’ve got money on Ashton, but I guess we’ll have to wait and see.

The bottom line according to Bray? “Mothering matters, but in moderation.”

Nature vs. Nurture and Addiction

Epigenetics involves modifications to DNA that do not change its sequence but only affect which genes are active, or expressed. Photo courtesy of whatisepigenetics.com

The progressive understanding of addiction as a disease rather than a choice has opened the door to better treatment and research, but there are aspects of addiction that make it uniquely difficult to treat.

One exceptional characteristic of addiction is its persistence even in the absence of drug use: during periods of abstinence, symptoms get worse over time, and response to the drug increases.

Researcher Elizabeth Heller, PhD, of the University of Pennsylvania Epigenetics Institute, is interested in understanding why we observe this persistence in symptoms even after drug use, the initial cause of the addiction, is stopped. Heller, who spoke at a Jan. 18 biochemistry seminar, believes the answer lies in epigenetic regulation.

Elizabeth Heller is interested in how changes in gene expression can explain the chronic nature of addiction.

Epigenetic regulation represents the nurture part of “nature vs. nurture.” Without changing the actual sequence of DNA, we have mechanisms in our body to control how and when cells express certain genes. These mechanisms are influenced by changes in our environment, and the process of influencing gene expression without altering the basic genetic code is called epigenetics.

Heller believes that we can understand the persistent nature of the symptoms of drugs of abuse even during abstinence by considering epigenetic changes caused by the drugs themselves.

To investigate the role of epigenetics in addiction, specifically cocaine addiction, Heller and her team have developed a series of tools to bind to DNA and influence expression of the molecules that play a role in epigenetic regulation, which are called transcription factors. They identified the FosB gene, which has been previously implicated as a regulator of drug addiction, as a site for these changes.

Increased expression of the FosB gene has been shown to increase sensitivity to cocaine, meaning individuals expressing this gene respond more than those not expressing it. Heller found that cocaine users show decreased levels of the protein responsible for inhibiting expression of FosB. This suggests cocaine use itself is depleting the protein that could help regulate and attenuate response to cocaine, making it more addictive.

Another gene, Nr4a1, is important in dopamine signaling, the reward pathway that is “hijacked” by drugs of abuse.  This gene has been shown to attenuate reward response to cocaine in mice. Mice who underwent epigenetic changes to suppress Nr4a1 showed increased reward response to cocaine. A drug that is currently used in cancer treatment has been shown to suppress Nr4a1 and, consequently, Heller has shown it can reduce cocaine reward behavior in mice.

The identification of genes like FosB and Nr4a1 and evidence that changes in gene expression are even greater in periods of abstinence than during drug use. These may be exciting leaps in our understanding of addiction, and ultimately finding treatments best-suited to such a unique and devastating disease.   

Post by undergraduate blogger Sarah Haurin

Post by undergraduate blogger Sarah Haurin

Using Genetic Clues to Reform Cardiac Care

Experiencing cardiac arrest can be compared to being in a hot air balloon in a room that is rapidly filling with water. You are trapped, desperately aware of the danger you are in, and running out of time.

Andrew Landstrom, PHD, MD, shared this metaphor with his audience in the Duke Medicine Pavilion last Thursday, and a wave of empathy flooded through his listeners. He works as an Assistant Professor of Pediatrics in Duke University’s School of Medicine, and devotes his time and energy to studying the genetic and molecular causes of sudden cardiac death in the young.

Andrew Landstrom, PHD, MD (Photo from Duke Center for Applied Genomics and Precision Medicine)

For families of children who have died suddenly and unexpectedly, the worst thing of all is hearing their doctors say, “we have no idea why.” A third of sudden death cases in children have negative autopsies, which means these children die with no explanation.

When faced with an inconclusive autopsy, everyone wants answers. Why did these children die? How do we know it’s a problem with the heart? What can be done about it? What does it mean for the siblings of the child who died?

It has since been discovered that many of these unexplained deaths are actually the result of cardiac channelopathies, which are DNA mutations that cause ion channel defects in heart cell proteins. These mutations can mess up the electrical activity of the heart and cause a heart to beat in an irregular rhythm, which can have fatal consequences. Since this is a molecular problem, and not a structural one, it cannot be identified with a conventional autopsy, and requires a deeper level of genetic and molecular analysis to be found.

One type of channelopathy is a condition known as CPVT, which is short for catecholaminergic polymorphic ventricular tachycardia. This potentially life-threatening genetic disorder is the result of a point mutation in the genome, which means that one tiny nucleotide being changed in the DNA can lead to the single most fatal arrhythmia (irregular heart rhythm) known to man.

Sixty percent of children suffering from CPVT have a mutation in their RYR2 gene. This gene encodes for a protein that is found in cardiac muscle, and is a key player in how calcium is processed in heart cells. The mutated version of this gene results in proteins that let way too much calcium flood the cell, which can cause fatal changes in heart rhythm.

Dr. Landstrom has been using genome research to identify and explain sudden cardiac death in children, but the human genome doesn’t always provide straightforward answers. The problem is, a mutation in the RYR2 gene doesn’t always mean a person will have CPVT, and having an incidental RYR2 gene is much more common than being diagnosed with CPVT. Dr. Landstrom is studying this gene to try to figure out which variants are pathologic, and which are physiological.

“The human genome is a lot more confusing than I think I gave it credit for, and we’re just learning to deal with that confusion now,” he admitted to his audience last Thursday.

The Components of the Human Genome (photo from NHS National Genetics and Genomics Education Centre)

If a variant is falsely identified as pathologic, a patient will be given incorrect therapies, and suffer through unnecessary procedures. However, if a variant is falsely identified as physiological, and the patient isn’t given the necessary treatment, there will be no mitigation of the patient’s life threatening disease. Neither of these are good outcomes, so it’s very important to get it right. The current models for predicting pathogenicity are poor, and Dr. Landstrom is looking to design new model that will be able to avoid the personal, subjective opinions of human doctors and determine if a variant is pathologic or not.

Could serotonin levels be used to predict an infant’s vulnerability to SIDS? (photo from Elmedir, Wikimedia Commons)

Another area that is of interest to Dr. Landstrom is the problem of Sudden Infant Death Syndrome (SIDS), which affects ~6 in every 10,000 infants, and cannot currently be diagnosed before death. He is on the search for a biomarker that would be able to predict an infant’s vulnerability to SIDS, and thinks that these deaths may be related to elevated levels of serotonin. Finding a marker like this would allow doctors to save many healthy infants from unexplained death. Dr. Landstrom knows its not easy research and admitted “we have to fail — we are meant to fail,” on the path to success. He is very aware of both the ethical complexity and the exciting implications of genome research at Duke, and committed to converting his research into patient care.

Post by Anne Littlewood

Pursuing Smell as a Path Into the Brain

Although the mystery of how the brain works and grows is a massive puzzle to figure out, the hope is that piece by piece, we can start to work towards a better understanding.

A person’s (or fly’s) sense of smell, or their olfactory system, is one of these pieces.

Though olfaction may not be the first part of the nervous system to cross someone’s mind when it comes to how we understand the brain, it is actually one of the most complex and diverse systems of an organism, and there’s a lot to understand within it, says Pelin Volkan, an assistant professor of biology and neurobiology and investigator in the Duke Institute for Brain Sciences.

Pelin Volkan in her lab.

Volkan and her lab have been working with fruit flies to try to unfold the many layers of the olfactory system, or the, “giant hairball,” as Volkan calls it.

Though she has been doing this work for years, she didn’t begin with an interest in neuroscience. Volkan was more interested in genetics in college and didn’t really start exploring neurobiology and development until her master’s degree at a Turkish university, when she worked with rats.

Not keen on working with rodents as model organisms but sticking with them anyway, she moved from Turkey to UNC to get her PhD, where she strayed away from neuroscience into molecular biology and development. Eventually, she realized she had a stronger passion for neuroscience, and ended up doing a postdoc at a Howard Hughes Medical Institute lab at UCLA for six years.

There, she became interested in receptors and neuronal wiring in the brain, propelling her to come to Duke and continue research on the brain’s connections and development.

One of the main reasons she loves working with the olfactory system is the many different scientific approaches that can be used to study it. Bouncing between using genetics, evolution, development, molecular biology,and other areas of study to understand the brain, her work is never static and she can take a more interdisciplinary approach to neuroscience where she is able to explore all the topics that interest her.

 Volkan says she has never had to settle on just one topic, and new questions are always arising that take her in directions she didn’t expect, which is what makes her current work particularly enjoyable for her.

“You have your stories, you close your stories, but then new questions come into play,” Volkan says. “And you have no choice but to follow those questions, so you just keep on going.”

And isn’t that what science is all about?

Guest Post by Angelina Katsanis, NCSSM 2019

An Indirect Path to Some Extreme Science

Dr. Cynthia Darnell’s path to becoming a postdoctoral researcher in the Amy Schmid Labat Duke University was, in her words, “not straightforward.”

Dr. Cynthia Darnell is a Postdoc at Duke, studying ‘extremophiles.’

At the start of her post-high school career, Darnell had no clue what she wanted to do, so she went to community college for the first two years while she decided. She had anticipated that she was going to go to college as an art major, but had always enjoyed biology.

While at community college she took a couple biology courses. She transferred to another college where she took a course in genetics and according to her, “it blew my mind.” While at the college she took a variety of different biology courses. Her genetics professor’s wife was looking for a lab technician in the microbiology lab she ran. After Darnell worked there for two years, she decided to go to graduate school and had a whole list of places/universities she could attend.

However, after going to a conference in Chicago and meeting her future graduate advisor, Darnell made the decision to go to Iowa for six years of Graduate school. She ended up in the Schmid Lab at Duke University for her “postdoc” after her boss had recommended the lab to her.

Previously, Darnell had done research on the connectedness of genetic pathways in halophilic extremophiles — bacteria that lived in extremely salty conditions. She developed projects to understand the how their genetic network sends and receives signals.

Darnell is continuing that research at Duke while also looking at the effects of different environmental factors on growth and the genetic network using mutant halophilic extremophiles.

Darnell with some plated archaebacteria in her Duke lab

There are generally three different paths Darnell’s day in the lab can take. The first path is a bench day. During a bench day, she will be doing experiments looking at growth curves, microscopes or RNA extracts. The second path is a computational day in which she will do sequencing to look at gene expression. The third option is a writing day in which she spends a majority of her time writing up grants, papers, and applications.

Dr. Darnell wishes to open up her own lab in the future and serve underprivileged students in underserved areas. She wishes to do more research in the area of archaebacteria because of how under researched and underrepresented it is in the scientific community. Dr. Darnell hopes to study more about the signaling networks in archaebacteria in her own lab someday.

She especially wishes to be able to open her lab up to underprivileged students, exposing them to the possibilities of research and graduate programs.

Guest Post by Tejaswi Siripurapu, NCSSM 2019

Tiny Bubbles of Bacterial Mischief

Margarethe (Meta) Kuehn studies vesicles — little bubbles that bud off bacterial membranes. All sorts of things may be tightly packed into these bubbles: viruses, antigens, and information a bacterium will need to make cells vulnerable to infection.

But why do bacteria produce these small membrane vesicles in the first place? Why not spread out to nearby cells themselves?

Jenny and Meta met last month on the Duke campus.

“The short answer is that we don’t know yet,” explains Kuehn, an associate professor of biochemistry at Duke. “But we speculate that it is due to their small size. These vesicles, which serve as delivery ‘bombs,’ can pass through pores that are too small for bacteria to fit through.”

Originally a chemistry major, Kuehn always had an interest in biochemistry. As an undergraduate, she worked in protein purification and then in the infectious disease division of a children’s hospital. There, she learned about pathogenic bacteria and how they secrete proteins to give themselves access to host cells.

Kuehn’s lab studies the mysterious world of bacterial vesicle production,focusing on the genetic, biochemical, and functional features of vesicles. So far, they have identified specific proteins and genes involved in the vesiculation process.

With a fine filter, they showed that vesicles can fit through holes to reach mammalian cells where a bacterium cannot.

Kuehn wonders why the bacteria don’t just use soluble proteins, which are even smaller than vesicles. They must have some reason for preferring the cell’s vesicles. Currently, they believe that vesicles can serve as nice packages — a whole bolus of information delivered together.

Basic anatomy of a vesicle, a bubble-like  membrane-bound package used by cells to move things around.

Not only will this new insight into extracellular vesicles of gram-negative bacteria aid in identifying new medicines, vesicles are also being used for vaccine delivery.

“They are really good antigen vehicles,” reveals Kuehn, “The more we know how they are made, the better we can design effective vaccines for humans.”

According to Kuehn, the amazing part about studying these pathogens is that, “You are never done. You never know it all. Every single pathogen, they each do things differently.” What keeps Kuehn going, she explains, is that the search never ends.

“There is never really a defined end point; you have to come to grips with the fact that you will never know that whole answer.”

Guest Post by Jenny Huang, NCSSM 2019

Biology by the Numbers

Michael C. Reed was trained as a pure mathematician, but from the start, he was, as he explained to me, a “closet physiologist.” He’s a professor of mathematics at Duke, but he’s always wondered how the body works.

Michael Reed in his office

Reed explains an example to me: women have elbows that are bent when their arms are straightened, but men do not. He rationalized his own explanation: women have wide hips and narrow shoulders; their bodies are designed so their arms don’t knock into their sides when they walk. (That basically ended up being the answer.)

Still, Reed never really explored his interest in physiology until he was 40 years old, when he realized that if he wanted to explore something, he should just do it. Why not? He had tenure by that point, so it didn’t really matter what his colleagues thought. He was interested in physiology, but was a mathematician. The obvious answer was mathematical biology.

Now he uses mathematics to find out how various physiological systems work.

In order to decide on a research project, he works with a biologist, Professor Fred Nijhout. They meet for two hours every day and work together. They have lots of projects, but they also just talk science sometimes. That’s how they get their ideas, mainly focusing on things in cell metabolism that have to do with important public health questions.

Reed has been investigating dopamine and serotonin metabolism in the brain, in a collaborative project with Nijhout and Dr. Janet Best, a mathematician at The Ohio State University.

Maybe better math is going to help us understand the human brain

As he explained to me, the brain isn’t like a computer; you don’t know how it works and there are a lot of systems in play. Serotonin is one of them. Low serotonin concentration is thought to be one of the causes of depression. There’s a biochemical network that synthesizes, packages, and transfers serotonin in the brain.

He told me that his work consists of making mathematical models for systems like this that consist of differential equations for concentrations of different chemicals. He then experiments with the system of differential equations to understand how the system works together. It’s not really something you can learn by having it explained to you, he told me. You have to learn through practice.

In a way, biology doesn’t seem like it would be the most compatible science, especially with math. But as Reed explained to me, “Math is easy because it’s very orderly and organized. If you work hard enough, you can understand it.” Biology, on the other hand, “is a mess.”

Everything in biology is linked to everything else in a system of connectedness that ends up all tangled together, and it can be hard to identify how something happens in the human body. But Reed applies math – an organized construct – to understand biological systems.

In the end, Reed does what he does because it’s how we — as human beings — work. He has no regrets about the choices he’s made at all.Mathematical biology seems to be his calling — he’s more interested in understanding how things work, and that’s what he does when he works.

Or rather, he doesn’t really work; because, as he told me,“try to find something to do that you really like, and are passionate about,because if you do, it won’t seem like work.” Reed doesn’t see coming into work as a struggle. He’s excited about it every single day and “it’s because you want to do it, it’s fun.”

Guest Post by Rachel Qu, NCSSM 2019

Gene-Editing Human Embryos: What, How, Why?

Every seat full. Students perched on the aisle stairs and lining the back walls.

What topic could possibly pull so many away from their final exams? Not “How to Stop Procrastinating” nor “How to Pass Life After Failing Your Exams” but rather “Gene-Editing Human Embryos: Unpacking the Current Controversy” on the Duke campus.

Since Chinese researcher He Jiankui announced at the Second International Summit on Human Genome Editing in Hong Kong that he made the world’s first genetically engineered babies, a debate on the ethical implications has raged on social media.

On December 6, the University Program in Genetics and Genomics and the Molecular Genetics and Microbiology department co-hosted a panel responding to He’s claims. Charles A. Gersbach from the Biomedical Engineering department lead the discussion of what exactly happened and then joined the panel which also contained Misha Angrist, a senior fellow in the Science & Society initiative;  Heidi Cope, a genetic counselor; Giny Fouda, an assistant professor in pediatrics; and Vandana Shashi, a genetic counselor.

Dr. He Jiankui announced he had used CRISPR to edit genes in twin embryos that were then born at full term.

But what exactly has He potentially done to these twin girls? Can they fly? Breathe underwater? Photosynthesize? Not exactly. He said he deleted a gene called CCR5 to increase their HIV resistance. Two percent of Northern Europeans naturally have a mutation that removes the CCR5 gene from their DNA and as a result do not display any traits other than increased HIV resistance.

Many researchers have explored blocking CCR5 activity as a potential HIV treatment. Using CRISPR-Cas9, a genetic engineering technology that can cut and paste specific sequences in the DNA, He targeted CCR5 during in vitro fertilization. According to his tests, he successfully removed both copies of the CCR5 gene in one of the girls. However, in the other girl, the CCR5 remained normal on one chromosome and on the other, CRISPR had deleted more than intended.  The effects of that additional deletion are unknown. 
Both the girls are mosaics, meaning the genetic change occurred in some of their cells and not in others, leading to still more uncertainties.

Researchers have conducted genetic engineering experiments on both somatic cells and human embryo cells that were never brought to term. (Somatic cells constitute all parts of the body other than the eggs and sperm.) But because He altered the twin girls as embryos and then they grew to full term, their children could inherit these changes. This alters their family line, not just a single individual, increasing the ethical implications.

According to Shashi, He’s experiment becomes difficult to justify. Additionally, embryos have not consented to these changes in their genetics, unlike a patient undergoing genetic therapy.

Many doctors, scientists, and journalists have also questioned He’s lack of transparency because he hid this work until his grand announcement, which caused China to arrest him. In addition, as Cope explained, “it is not typically the PI who does the informed consent process” as He did with these parents.

While He defends his work by saying that the girls’ father carries HIV and wished to increase the girls’ safety, the twins were not actually at great risk for HIV. Their father’s medical history does not increase their chances of contracting the virus, and the overall risk for HIV in China is low. As Fouda emphasized in the panel, “there was no justification for this experiment.” While He discussed the potential for genetic engineering to help society, for these two individuals, no medical need existed, and that increases the ethical dilemma.

A final concern of researchers is the current inability to ensure technical competency and accuracy. As seen by the additional deletion in one of the girls,  CRISPR-Cas9 still makes errors. Thus using it to alter not only a human being but all of that individual’s progeny would demand a much higher standard, something close to a life-or-death scenario.

But, the panelists also noted, if it hadn’t been He, it would have been somebody else. Perhaps somebody else may have done it more ethically with more transparency and a more traditional consent process, Angrist said.

While He’s claims have yet to be proven, the fact that they could reasonably be true has many concerned. The World Health Organization has announced that they will begin greater oversight of genetic engineering of the human germline.

On campus over the last weeks, I’ve heard mixed reviews on He’s work with some joking about future superhero babies while others have reacted with fear. The technology does live among us; however, the world is working on writing the guidebook and unrolling the yellow tape.

Post by Lydia Goff

Sean Carroll on the Evolution of Snake Venom

What’s in a snake bite?

According to University of Wisconsin-Madison evolutionary biologist Sean Carroll who visited Duke and Durham last week, a snake bite contains a full index of clues.

In his recent research, Carroll has been studying the adaptations of novelties in animal form, such as snake venom. Rattlesnakes, he explains, are the picture of novelty. With traits such as a limbless body, fangs, infrared pits, patterned skin, venom, and the iconic rattle, they represent an amazing incarnation of evolution at work.

Rattlesnakes: the picture of novelty (Photo from USGS)

Snake venoms contain a complex mixture of proteins. This mixture can differ in several ways, but the most interesting difference to Carroll is the presence or absence of neurotoxins. Neurotoxic venom has proven to be a very useful trait, because neurotoxins destroy the nervous tissue of prey, effectively paralyzing the animal’s respiratory system.

Some of today’s rattlesnake species have neurotoxic venom, but some don’t. So how did this happen? That’s what Carroll was wondering too.

Some genes within genomes, such as HOX genes, evolve very slowly from their original position among the chromosomes, and see very few changes in the sequence in millions of years.

But snake venom Pla2 genes are quite the opposite. In recent history, there has been a massive expansion of these genes in the snake genome, Carroll said. When animals evolve new functions or forms, the question always arises: are these changes the result of brand new genes or old genes taking on new functions?

Another important consideration is the concept of regulatory versus structural genes. Regulatory genes control the activity of other genes, such as structural genes, and because of this, duplicates of regulatory genes are generally not going to be a favorable adaptation. In contrast, structural gene activity doesn’t affect other genes, and duplicates are often a positive change. This means it is easier for a new structural gene to evolve than a regulatory one. Carroll explained.

Evolutionary Biologist Sean Carroll (Photo from seanbcarroll.com)

Carroll examined neurotoxic and non-neurotoxic snakes living in overlapping environments. His research showed that the most recent common ancestor of these species was a snake with neurotoxic venom. When comparing the genetic code of neurotoxic snakes to non-neurotoxic ones, he found that the two differed by the presence or absence of 16 genes in the metalloproteinase gene complex. He said this meant that non-neurotoxic venom could not evolve from neurotoxic venom.

So what is the mechanism behind this change? What could be the evolutionary explanation?

When Carroll’s lab compared another pair of neurotoxic and non-neurotoxic species in a different region of the US, they found that the two species differed in exactly the same way, with the same set of genes deleted as had been observed in the first discovery. With this new information, Carroll realized that the differences must have occurred through the mechanism of hybridization, or the interbreeding of neurotoxic and non-neurotoxic species.

Carroll’s lab is now doing the structural work to study if the genes that result in neurotoxic and  non-neurotoxic protein complexes are old genes carrying out new functions or entirely new genes. They are using venom gland organoids to look into the regulatory processes of these genes.

In addition to his research studying the evolution of novelties, Carroll teaches molecular biology and genetics at Madison and has devoted a large portion of his career to  storytelling and science education.

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