Duke Research Blog

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

Author: Lydia Goff Page 1 of 2

The Making of queerXscape

Sinan Goknur

On September 10th, queerXscape, a new exhibit in The Murthy Agora Studio at the Rubenstein Arts Center, opened. Sinan Goknur and Max Symuleski, PhD candidates in the Computational Media, Arts & Cultures Program, created the installation with digital prints of collages, cardboard structures, videos, and audio. Max explains that this multi-media approach transforms the studio from a room into a landscape which provides an immersive experience.

Max Symuleski

The two artists combined their experiences with changing urban environments when planning this exhibit. Sinan reflects on his time in Turkey where he saw constant construction and destruction, resulting in a quickly shifting landscape. While processing all of this displacement, he began taking pictures as “a way of coping with the world.” These pictures later become layers in the collages he designed with Max.

Meanwhile, Max used their time in New York City where they had to move from neighborhood to neighborhood as gentrification raised prices. Approaching this project, they wondered, “What does queer mean in this changing landscape? What does it mean to queer something? Where are our spaces? Where do we need them to survive?” They had previously worked on smaller collages made from magazines that inspired the pair of artists to try larger-scale works.  

Both Sinan and Max have watched the exploding growth in Durham while studying at Duke. From this perspective, they were able to tackle this project while living in a city that exemplifies the themes they explore in their work.

One of the cardboard structures

Using a video that Sinan had made as inspiration for the exhibit, they began assembling four large digital collages. To collaborate on the pieces, they would send the documents back and forth while making edits. When it became time to assemble their work, they had to print the collage in large strips and then careful glue them together. Through this process, they learned the importance of researching materials and experimented with the best way to smoothly place the strips together. While putting together mound-like cardboard structures of building, tire, and ice cube cut-outs, Max realized that, “we’re now doing construction.” Consulting with friends who do small construction and maintenance jobs for a living also helped them assemble and install the large-scale murals in the space. The installation process for them was yet another example of the tension between various drives for and scales of constructions taking place around them.

While collage and video may seem like an odd combination, they work together in this exhibit to surround the viewer and appeal to both the eyes and ears. Both artists share a background in queer performance and are driven to the rough aesthetics of photo collage and paper. The show brings together aspects of their experience in drag performance, collage, video, photography, and paper sculpture of a balanced collaboration. Their work demonstrates the value of partnership that crosses genres.

Poster for the exhibit

When concluding their discussion of changing spaces, Max mentioned that, “our sense of resilience is tied to the domains where we could be queer.” Finding an environment where you belong becomes even more difficult when your landscape resembles shifting sand. Max and Sinan give a glimpse into the many effects of gentrification, destruction, and growth within the urban context. 

The exhibit will be open until October 6. If you want to see the results of weeks of collaging, printing, cutting, and pasting together photography accumulated from near and far, stop by the Ruby.

Post by Lydia Goff

Overcoming Judgment Biases in STEM

Beginning in childhood we all develop unconscious stereotypes that influence how we see ourselves and others – including what careers we choose, and who we choose to recruit, hire or promote in the workplace.

Researchers discussed the origins and effects of these judgement biases during a virtual conference titled Mitigating Implicit Bias: Tools for the Neuroscientist, which was put on by the Society for Neuroscience and screened by DIBS at Duke on Jan. 23 and 24.

Associate professor of neuroscience Anne Churchland of Cold Spring Harbor Laboratory proposed several ideas for overcoming gender bias in the workplace, especially for women in STEM or other male-dominated domains. Asking questions, speaking with authority (particularly about one’s own work), finding a way to communicate with senior colleagues, trying risky experiments, making one’s achievements known, sending one’s work to high-level journals, and applying to awards and grants are her main suggestions. Above all these strategies, she recommends finding good friends and colleagues to help. As research shows, when women are successful in arenas that are viewed as distinctly male, both women and men like them less. These negative reactions can be discouraging and even career-affecting, and any support system will help to overcome that struggle.

The ‘Brilliance Barrier ‘ is a judgement bias explored by Andrei Cimpian’s research at New York University. One study shows that for every ten parents who searched on Google, “Is my daughter talented?”, twenty-five parents looked up “Is my son talented?”

Another study describes the gendered reviews on ratemyprofessor.com. Men are two to three times more likely to be called genius than women. Women though are more likely to be portrayed as warm or caring.

Cimpian uses these studies to develop the Field-specific Ability Beliefs hypothesis (FAB). FAB attributes women’s underrepresentation to a combination of the idolized brilliance/genius and the “brilliance” equals men stereotype. The higher the FAB in a field, the greater the emphasis on brilliance in it. When graphing the percentage of women with PhDs and the FAB for a specific field such as philosophy or physics, higher FABs are associated with a lower number of PhDs. African American representation also decreases as the FAB increases. Cimpian classifies one potential mechanism of this trend as minorities having less interest in fields with high FABs. In addition, increased bias, discrimination, and imposter syndrome could explain why minorities appear to avoid getting PhDs in high FAB fields.

Cimpian also demonstrates how susceptible children are to judgement biases. At age five, the percentage of girls who pick their own gender as “really, really smart” and the percentage of boys who do the same are similar. When children reach seven though, the percentage of boys choosing men exceeds the girls picking women. He suggests de-emphasizing brilliance, genius, and gifted in favor of work ethic because minorities are more likely to be recommended when the job description asks for commitment than when it asks for intelligence. Language has the potential to change the amount of representation in high FAB fields, such as STEM.

Image result for jackie fleming cartoons
Never Give Up – Cartoon by Jackie Fleming

Lastly, psychology professor Ione Fine at the University of Washington talked about the hiring process in her lab and how she reduces bias by laying out and weighting criteria beforehand. Instead of focusing on objective criteria like GPA and GRE scores, she advocates for more interviews with set lists of questions and a paper discussion. She also recommends calling the recommendation letter writers. After selecting a diverse group of research assistants, Fine then makes sure they have the proper support and mentoring. Reinforcing that they were chosen for their potential and that she is their advocate helps them feel empowered to succeed in her lab. Through mentoring and supporting diversity, anyone can help minorities overcome the judgement biases surrounding them.   

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

Coding: A Piece of Cake

Image result for cake

Imagine a cake, your favorite cake. Has your interest been piqued?

“Start with Cake” has proved an effective teaching strategy for Mine Cetinkaya-Rundel in her introduction-level statistics classes. In her talk “Teaching Computing via Visualization,” she lays out her classroom approaches to helping students maintain an interest in coding despite its difficulty. Just like a cooking class, a taste of the final product can motivate students to master the process. Cetinkaya-Rundel, therefore, believes that instead of having students begin with the flour and sugar and milk, they should dive right into the sweet frosting. While bringing cake to the first day of class has a great success rate for increasing a class’s attention span (they’ll sugar crash in their next classes, no worries), what this statistics professor actually refers to is showing the final visualizations. By giving students large amounts of pre-written code and only one or two steps to complete during the first few class periods, they can immediately recognize coding’s potential. The possibilities become exciting and capture their attention so that fewer students attempt to vanish with the magic of drop/add period. For the student unsure about coding, immediately writing their own code can seem overwhelming and steal the joy of creating.

Example of a visualization Cetinkaya-Rundel uses in her classes

To accommodate students with less background in coding, Cetinkaya-Rundel believes that skipping the baby steps proves a better approach than slowing the pace. By jumping straight into larger projects, students can spend more time wrestling their code and discovering the best strategies rather than memorizing the definition of a histogram. The idea is to give the students everything on day one, and then slowly remove the pre-written coding until they are writing on their own. The traditional classroom approach involves teaching students line-by-line until they have enough to create the desired visualizations. While Cetinkaya-Rundel admits that her style may not suit every individual and creating the assignments does require more time, she stands by her eat-dessert-first perspective on teaching. Another way she helps students maintain their original curiosity is by cherishing day one through pre-installed packages which allow students to start playing with visualizations and altering code right away.

Not only does Cetinkaya-Rundel give mouth-watering cakes as the end results for her students but she also sometimes shows them burnt and crumbling desserts. “People like to critique,” she explains as she lays out how to motivate students to begin writing original code. When she gives her students a sloppy graph and tells them to fix it, they are more likely to find creative solutions and explore how to make the graph most appealing to them. As the scaffolding falls away and students begin diverging from the style guides, Cetinkaya-Rundel has found that they have a greater understanding of and passion for coding. A spoonful of sugar really does help the medicine go down.  

    Post by Lydia Goff

Becoming the First: Nick Carnes

Editor’s Note: In the “Becoming the First” series,  first-generation college student and Rubenstein Scholar Lydia Goff explores the experiences of Duke researchers who were the first in their families to attend college.

A portrait of Duke Professor Nick Carnes

Nick Carnes

Should we care that we are governed by professionals and millionaires? This is one of the questions Nick Carnes, an assistant professor in the Sanford School of Public Policy, seeks to answer with his research. He explores unequal social class representation in the political process and how it affects policy making. But do any real differences even exist between politicians from lower socioeconomic classes and those from the upper classes? Carnes believes they do, not only because of his research but also because of his personal experiences.

When Carnes entered Princeton University as a political science graduate student, he was the only member of his cohort who had done restaurant, construction or factory work. While obtaining his undergraduate degree from the University of Tulsa, he worked twenty hours a week and during the summer clocked in at sixty to seventy hours a week between two jobs. He considered himself and his classmates “similar on paper,” just like how politicians from a variety of socioeconomic classes can also appear comparable. However, Carnes noticed that he approached some problems differently than his classmates and wondered why. After attributing his distinct approach to his working class background, without the benefits of established college graduate family members (his mother did go to college while he was growing up), he began developing his current research interests.

Carnes considers “challenging the negative stereotypes about working class people” the most important aspect of his research. When he entered college, his first meeting with his advisor was filled with confusion as he tried to decipher what a syllabus was. While his working class status did restrict his knowledge of college norms, he overcame these limitations. He is now a researcher, writer, and professor who considers his job “the best in the world” and whose own story proves that working class individuals can conquer positions more often inhabited by the experienced. As Carnes states, “There’s no good reason to not have working class people in office.” His research seeks to reinforce that.

His biggest challenge is that the data he needs to analyze does not exist in a well-documented manner. Much of his research involves gathering data so that he can generate results. His published book, White-Collar Government: The Hidden Role of Class in Economic Policy Making, and his book coming out in September, The Cash Ceiling: Why Only the Rich Run for Office–and What We Can Do About It, contain the data and results he has produced. Presently, he is beginning a project on transnational governments because “cash ceilings exist in every advanced democracy.” Carnes’ research proves we should care that professionals and millionaires run our government. Through his story, he exemplifies that students who come from families without generations of college graduates can still succeed.    

 

Post by Lydia Goff

 

Becoming the First: Erika Weinthal

Editor’s Note: In the “Becoming the First” series,  first-generation college student and Rubenstein Scholar Lydia Goff explores the experiences of Duke researchers who were the first in their families to attend college.

A portrait of Erika Weinthal

Erika Weinthal

In her corner office with a wall of windows and stuffed bookshelves, Erika Weinthal keeps a photo of her father. He came to the United States from Germany in 1940. And for a German Jew, that was extremely late. According to the family stories, Weinthal’s father left on the second to last boat from Italy. It is no surprise that he was never a big traveler after his arrival to America. As Weinthal describes it, “America…was the country that saved him.” Not only did it protect him, but it also gave his children opportunities that he did not have, such as going to college.

Weinthal, Lee Hill Snowdon Professor of Environmental Policy in Duke’s Nicholas School of the Environment, took this opportunity to become the first in her family to attend college, launching her career researching environmental policy and water security in areas including the former Soviet Union, Middle East, East Africa, India and the United States.

In high school, Weinthal traveled as an exchange student to Germany, a country her relatives could never understand her desire to visit. “As a child of a refugee, you didn’t talk about the war,” she explains as she describes how this silence created her curiosity about what happened. That journey to Bremen marked only the first of many trips around the world. In the Middle East, she examines environmental policy between countries that share water. In India, she has researched the relationship between wildlife and humans near protected areas. “What do you do when protected wildlife destroys crops and threatens livelihoods?” she asks, proving that since her curiosity about the war, she has not stopped asking questions.

However, her specific interest in environmental science and policy came straight from a different war: the Cold War. She became obsessed with everything Russian partly thanks to a high school teacher who agreed to teach her Russian one-on-one. The teacher introduced Weinthal to Russian literature and poetry. While her parents, like many parents, would have loved for her to become a doctor or a lawyer, they still trusted her when she enrolled in Oberlin College intent on studying Soviet politics. A class on Soviet environment politics further increased her interest in water security.

Currently, her work contends that water should be viewed as a basic human need separate from the political conflicts in Palestine and Israel. She has studied how protracted conflict in the region has led to the deterioration of water quality in the Gaza Strip, creating a situation in which water is now unfit for human consumption. Weinthal argues that these regions should not view water as property to be secured but rather as a human right they should guarantee.

Erika Weinthal’s father in 1940

As a child of a refugee and a first-generation college student, Weinthal says “you grow up essentially so grateful for what others have sacrificed for you.” Her dad believed in giving back to the next generation. He accomplished that goal and, in the process, gave the world a researcher who’s invested in environmental policy and human rights.

Post by Lydia Goff

 

DNA Breakage: What Doesn’t Kill You…

What doesn’t kill you makes you stronger―at least according to Kelly Clarkson’s recovery song for middle school crushes, philosopher Friedrich Nietzsche, and New York University researcher Viji Subramanian.

During the creation of sperm or eggs, DNA molecules exchange genetic material. This increases the differences between offspring and their parents and the overall species diversity and is thought to make an individual and a species stronger.

However, to trade genetic information — through a process called recombination — the DNA molecules must break at points along the chromosomes, risking permanent damage and loss of genomic integrity. In humans, errors during recombination can lead to infertility, fetal loss, and birth defects.

Subramanian, a postdoctoral researcher in the lab of Andreas Hochwagen at NYU, spoke at Duke on February 26. She studies how cells prevent excessive DNA breakage and how they regulate repair.

Subramanian uses budding yeast to study the ‘synaptonemal complex,’ a structure that forms between pairing chromosomes as shown in the above image. Over three hundred DNA breakage hotspots exist in the budding yeast’s synaptonemal complex. Normally, double-stranded DNA breaks go from none to some and then return to none.

However, when Subramanian removed the synaptonemal complex, the breaks still appeared, but they did not completely disappear by the end of the process. She  concluded that synaptonemal complex shuts down DNA break formation. The synaptonemal complex therefore is one way cells prevent excessive DNA breakage.

The formation of the synaptonemal complex

 

During DNA breakage repair, preference must occur between the pairing chromosomes in order for recombination to correctly transpire. A protein called Mek1 promotes this bias by suppressing DNA in select areas. Early in the process of DNA breakage and repair Mek1 levels are high, while synaptonemal complex density is low. Later, the synaptonemal complex increases while the Mek1 decreases.

This led to Subramanian’s conclusion that synaptonemal complex is responsible for removing Mek1, allowing in DNA repair. She then explored if the protein pch2 regulates the removal of Mek1. In pch2-mutant budding yeast cells, DNA breaks were not repaired.

Subramanian showed that at least one aspect of DNA breakage and repair occurs through the Mek1 protein suppression of repair, creating selectivity between chromosomes. The synaptonemal complex then uses pch2 to remove Mek1 allowing DNA breakage repair.

Subramanian had another question about this process though: how is breakage ensured in small chromosomes? Because there are fewer possible breaking points, the chance of recombination seems lower in small chromosomes. However, Subramanian discovered that zones of high DNA break potential exist near the chromosome ends, allowing numerous breaks to form even in smaller chromosomes. This explains why smaller chromosomes actually exhibit a higher density of DNA breaks and recombination since their end zones occupy a larger percentage of their total surface area.

In the future, Subramanian wants to continue studying the specific mechanics behind DNA breaks and repair, including how the chromosomes reorganize during and after this process. She is also curious about how Mek1 suppresses repair and has more than 200 Mek1 mutants in her current study.

Kelly Clarkson may prove that heartbreaks don’t destroy you, but Viji Subramanian proves that DNA breaks create a stronger, more unique genetic code.         

Post by Lydia Goff

        

Obesity: Do Your Cells Have a Sweet Tooth?

Obesity is a global public health crisis that has doubled since 1980. That is why Damaris N. Lorenzo, a professor of  Cell Biology and Physiology at UNC-Chapel Hill, has devoted her research to this topic.

Specifically, she examines the role of ankyrin-B variants in metabolism. Ankyrins play a role in the movement of substances such as ions into and out of the cell. One of the ways that ankyrins affect this movement is through the glucose transporter protein GLUT4 which is present in the heart, skeletal muscles, and insulin-responsive tissues. GLUT4 plays a large role in glucose levels throughout the entire body.

Through her research, Lorenzo discovered that with modern life spans and high calorie diets, ankyrin-B variants can be a risk factor for metabolic disease. She presented her work for the Duke Developmental & Stem Cell Biology department on March 7th.

Prevalence of Self-Reported Obesity Among U.S. Adults by State, 2016

GLUT4 helps remove glucose from the body’s circulation by moving it into cells. The more GLUT4, the more sugar cells absorb.

Ankyrin-B’s role in regulating GLUT4 therefore proves really important for overall health. Through experiments on mice, Lorenzo discovered that mice manipulated to have ankyrin-B mutations also had high levels of cell surface GLUT4. This led to increased uptake of glucose into cells. Ankyrin-B therefore regulates how quickly glucose enters adipocytes, cells that store fat. These ankyrin-B deficient mice end up with adipocytes that have larger lipid droplets, which are fatty acids.

Lorenzo was able to conclude that ankyrin-B deficiency leads to age-dependent obesity in mutant mice. Age-dependent because young ankyrin-B mutant mice with high fat diets are actually more likely to be affected by this change.

Obese mouse versus a regular mouse

Ankyrin-B has only recently been recognized as part of GLUT4 movement into the cell. As cell sizes grow through increased glucose uptake, not only does the risk of obesity rise but also inflammation is triggered and metabolism becomes impaired, leading to overall poor health.

With obesity becoming a greater problem due to increased calorie consumption, poor dietary habits, physical inactivity, environmental and life stressors, medical conditions, and drug treatments, understanding factors inside of the body can help. Lorenzo seeks to discover how ankyrin-B protein might play a role in the amount of sugar our cells internalize.

Post by Lydia Goff

How a Museum Became a Lab

Encountering and creating art may be some of mankind’s most complex experiences. Art, not just visual but also dancing and singing, requires the brain to understand an object or performance presented to it and then to associate it with memories, facts, and emotions.

A piece in Dario Robleto’s exhibit titled “The Heart’s Knowledge Will Decay” (2014)

In an ongoing experiment, Jose “Pepe” Contreras-Vidal and his team set up in artist Dario Robleto’s exhibit “The Boundary of Life Is Quietly Crossed” at the Menil Collection near downtown Houston. They then asked visitors if they were willing to have their trips through the museum and their brain activities recorded. Robleto’s work was displayed from August 16, 2014 to January 4, 2015. By engaging museum visitors, Contreras-Vidal and Robleto gathered brain activity data while also educating the public, combining research and outreach.

“We need to collect data in a more natural way, beyond the lab” explained Contreras-Vidal, an engineering professor at the University of Houston, during a talk with Robleto sponsored by the Nasher Museum.

More than 3,000 people have participated in this experiment, and the number is growing.

To measure brain activity, the volunteers wear EEG caps which record the electrical impulses that the brain uses for communication. EEG caps are noninvasive because they are just pulled onto the head like swim caps. The caps allow the museum goers to move around freely so Contreras-Vidal can record their natural movements and interactions.

By watching individuals interact with art, Contreras-Vidal and his team can find patterns between their experiences and their brain activity. They also asked the volunteers to reflect on their visit, adding a first person perspective to the experiment. These three sources of data showed them what a young girl’s favorite painting was, how she moved and expressed her reaction to this painting, and how her brain activity reflected this opinion and reaction.

The volunteers can also watch the recordings of their brain signals, giving them an opportunity to ask questions and engage with the science community. For most participants, this is the first time they’ve seen recordings of their brain’s electrical signals. In one trip, these individuals learned about art, science, and how the two can interact. Throughout this entire process, every member of the audience forms a unique opinion and learns something about both the world and themselves as they interact with and make art.

Children with EEG caps explore art.

Contreras-Vidal is especially interested in the gestures people make when exposed to the various stimuli in a museum and hopes to apply this information to robotics. In the future, he wants someone with a robotic arm to not only be able to grab a cup but also to be able to caress it, grip it, or snatch it. For example, you probably can tell if your mom or your best friend is approaching you by their footsteps. Contreras-Vidal wants to restore this level of individuality to people who have prosthetics.

Contreras-Vidal thinks science can benefit art just as much as art can benefit science. Both he and Robleto hope that their research can reduce many artists’ distrust of science and help advance both fields through collaboration.

Post by Lydia Goff

MyD88: Villain of Allergies and Asthma

Even if you don’t have allergies yourself, I guarantee you can list at least three people you know who have allergies. Asthma, a respiratory disorder commonly associated with allergies, afflicts over 300 million individuals worldwide.

Seddon Y. Thomas, PhD of the NIEHS

Seddon Y. Thomas, PhD of the NIEHS

Seddon Y. Thomas who works at the National Institute of Environmental Health Sciences has been exploring how sensitization to allergens occurs. The work, which she described at a recent  session of the Immunology Seminar Series, specifically focuses on the relationship between sensitization and the adaptor molecule MyD88.

MyD88 transfers signals between some of the proteins and receptors that are involved in immune responses to foreign invaders. Since allergies entail inflammation caused by an immune response, Thomas recognized that MyD88 played a role in the immune system’s sensitization to inhaled allergens.

Her research aims to discover how MyD88 alters conventional dendritic cells (cDCs) which are innate immune cells that drive allergic inflammation. MyD88 signaling in cDCs sometimes preserves open chromatin — the availability of DNA for rapid replication — which allows gene changes to happen quickly and in turn causes allergic sensitization. Open chromatin regions permit the DNA manipulation that can lead to allergies and asthma. 

Florescence microscopy image of mouse dendritic cells with mRNA-loaded blood cells.

To conduct her experiments, Thomas examines what happens in mice when she deletes MyD88 from lung epithelial cells and from antigen-presenting cells. Lung epithelial cells form a protective tissue where inhaled air meets the lung and protects from foreign invaders. But sometimes it takes its job a little too seriously and reacts strongly to allergens.

Similarly, antigen-presenting cells are involved in the immune system’s mission to protect the body, but can become confused about who the enemy is. When the signaling adaptor MyD88 is removed from lung epithelial cells, the number of eosinophils, inflammatory white blood cells, decreases. When it is removed from antigen-presenting cells, another type of white blood cell, neutrophils, also decreases.

Thomas said this shows that MyD88 is necessary for the inflammation in the lungs that causes asthma and allergies.

In her future research, Thomas wishes to explore dendritic cell gene expression, the molecular pathways controlling gene expression, and how specific types of lung epithelial cells adjust immune responses. Because MyD88 plays a role in the genetic changes, it makes sense to continue research on the genetic side.    

Post by Lydia Goff            

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