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

Students exploring the Innovation Co-Lab

Author: Lydia Goff

Morphogenesis: All Guts and Morning Glories

What is morphogenesis? Morphogenesis examines the development of the living organisms’ forms.

It also is an area of research for Lakshminarayanan Mahadevan, Professor of Applied Mathematics, Organismic and Evolutionary Biology and Physics at Harvard University. On his presentation in the Public Lectures Unveiling Math (PLUM) series here at Duke, he credited the beginnings of morphogenesis to D’Arcy Wentworth Thompson, author of the book On Growth and Form.

Mathematically, morphogenesis focuses on how different rates of growth change the shapes of organisms as they develop. Cell number, cell size, cell shape, and cell position comprise the primary cellular factors of multicellular morphogenesis, which studies larger structures than individual cells and is Mahadevan’s focus.

Effects on tissues appear through changes in sizes, connectivities, and shapes, altering the phenotype, or the outward physical appearance. All these variables change in space and time. Professor Mahadevan presented on morphogenesis studies that have been conducted on plant shoots, guts, and brains.

Research on plant shoots often concentrates on the question, “Why do plant shoots grow in such a wide variety of directions and what determines their shapes?” The picture below shows the different postures appearances of plant shoots from completely straight to leaning to hanging.

Can morphogenesis make sense of these differences? Through mathematical modeling, two stimuli for shoots’ shapes was determined: gravity and itself. Additionally, elasticity as a function of the shoots’ weight plays a role in the mathematical models of plant shoots’ shapes which appear in Mahadevan’s paper co-written with a fellow professor, Raghunath Chelakkot. Mahadevan also explored the formation of flower and leaf shapes with these morphogenesis studies. 

Over twenty feet of guts are coiled up inside you. In order to fit these intestines inside the mammals, they must coil and loop. But what variables determine how these guts loop around? To discover the answer to this question, Mahadevan and other researchers examined chick embryos which increase their gut lengths by a factor greater than twenty over a twelve-day span. They were able to create a physical model using a rubber tube sewn to a sheet that followed the same patterns as the chicks’ guts. Through their observation of not only chicks but also quail and mice, Mahadevan determined that the morphogenesis of the guts has no dependence on genetics or any other microscopic factors.

Mahadevan’s study of how the brain folds occurs through MRI images of human fetal development. Initially, barely any folding exists on fetal brains but eventually the geometry of the surrounding along with local stress forms folds on the brain. By creating a template with gel and treating it to mimic the relationship between the brain’s gray matter and white matter, Mahadevan along with other researchers discovered that they could reproduce the brain’s folds. Because they were able to recreate the folds through only global geometry and local stress, they concluded that morphogenesis evolution does not depend on microscopic factors such as genetics. Further, by examining if folding regions correlate with the activity regions of the brain, questions about the effect of physical form on abilities and the inner functions of the brain.

  

     

Scavenger Receptors in Environmental Lung Disease

“Lung disease causes 15% of deaths worldwide” Kymberly Gowdy explained in her lecture at Duke,  “Clean Up and Clear Out: A Novel Role for Scavenger Receptors in Environmental Lung Disease.”

In her research, she applies her training as an immunologist to analyze immune responses to environmental challenges and their role in lung disease. Gowdy is an Assistant Professor at East Carolina University where her research specifically focuses on scavenger receptors (SRs). SRs are pattern recognition receptors that recognize and bind cellular debris and pathogens. Gowdy’s research focuses on scavenger receptor SR-B1 and SR-CD163.

Kymberly Gowdy of East Carolina University

Kymberly Gowdy of East Carolina University

Her experiments with SR-B1 have shown that knockout mice (mice without the scavenger receptor B1) have increased mortality rates after pulmonary infection, as shown in the figure below. After examining different causes of this increase in mortality, Gowdy and her lab concluded that the cause was an increase in bacterial burden.

The pattern they detected revealed that an increase of bacteria in the blood correlates to both an increase in cytokines (substances secreted by immune cells that create inflammation and respond to infections) and an increase in mortality. Gowdy also associated a decrease in clearance in the lungs with this trend, which explains why pneumonia does not heal and therefore leads to death.

Gowdy’s lab also explored the possibility for a connection between SR-B1 and ozone-induced respiratory and cardiovascular inflammation. She discovered a positive correlation between SR-B1, the oxidization of lipids in the lungs, and pulmonary inflammation. She concludes that SR-B1 expression is protective against air pollutant exposure such as ozone.

Mice lacking SR-B1 (dashed line) only survived two days after an infection challenged their lungs.

Gowdy has also investigated a receptor called SR-CD163 which clears hemoglobin and haptoglobin (Hb-Hp) from the lungs. This receptor protects organs from cell-free hemoglobin preventing damage. When she exposed knockout mice without SR-CD163 to ozone, she discovered an increase in the pulmonary levels of cell-free hemoglobin. Similarly to experiments with SR-B1, the CD163-deficient mice demonstrated patterns of increased lung damage as they experienced increased exposure to ozone.

Through her collaboration with laboratories at Duke, Gowdy has been able to discover that ozone exposure increases the response of pulmonary CD163 in mice and humans.

Gowdy’s work has shown the existence of direct relationships between environmental factors such as ozone and the levels of scavenger receptors such as B1 and CD163 in the lungs. The complex association between immune responses and lung diseases creates an interesting field of research, particularly when explored through the lens of environmental triggers.

Gowdy’s results reveal the intricacy of the immune system. An inflammatory response is meant to protect an individual’s health, but too much immune activation in the lungs can lead to disease.

Post by Lydia Goff.

Who Gets Sick and Why?

During his presentation as part of the Chautauqua lecture series, Duke sociologist Dr. Tyson Brown explained his research exploring the ways racial inequalities affect a person’s health later in life. His project mainly looks at the Baby Boomer generation, Americans born between 1946 and 1964.

With incredible increases in life expectancy, from 47 years in 1900 to 79 today, elderly people are beginning to form a larger percentage of the population. However among black people, the average life expectancy is three and a half years shorter.

“Many of you probably do not think that three and half years is a lot,” Brown said. “But imagine how much less time that is with your family and loved ones. In the end, I think all of us agree we want those extra three and a half years.”

Not only does the black population in America have shorter lives on average but they also tend to have sicker lives with higher blood pressures, greater chances of stroke, and higher probability of diabetes. In total, the number of deaths that would be prevented if African-American people had the same life expectancy as white people is 880,000 over a nine-year span. Now, the question Brown has challenged himself with is “Why does this discrepancy occur?”

Brown said he first concluded that health habits and behaviors do not create this life expectancy gap because white and black people have similar rates of smoking, drinking, and illegal drug use. He then decided to explore socioeconomic status. He discovered that as education increases, mortality decreases. And as income increases, self-rated health increases. He said that for every dollar a white person makes, a black person makes 59 cents.

This inequality in income points to the possible cause for the racial inequality in health, he said.  Additionally, in terms of wealth instead of income, a black person has 6 cents compared to the white person’s dollar. Possibly even more concerning than this inconsistency is the fact that it has gotten worse, not better, over time. Before the 2006 recession, blacks had 10-12 cents of wealth for every white person’s dollar.

Brown believes that this financial stress forms one of many stressors in black lives including chronic stressors, everyday discrimination, traumatic events, and neighborhood disorder which affect their health.

Over time, these stressors create something called physiological dysregulation, otherwise known as wear and tear, through repeated activation of  the stress response, he said. Recognition of the prevalence of these stressors in black lives has lead to Brown’s next focus on the extent of the effect of stressors on health. For his data, he uses the Health and Retirement Study and self-rated health (proven to predict mortality better than physician evaluations). For his methods, he employs structural equation modeling. Racial inequalities in socioeconomic resources, stressors and biomarkers of physiological dysregulation collectively explain 87% of the health gap with any number of causes capable of filling the remaining percentage.

Brown said his next steps include using longitudinal and macro-level data on structural inequality to understand how social inequalities “get under the skin” over a person’s lifetime. He suggests that the next steps for society, organizations, and the government to decrease this racial discrepancy rest in changing economic policy, increasing wages, guaranteeing work, and reducing residential segregation.

Post by Lydia Goff

Global Health Research from Zika to Economics

Brazil, Kenya and China: this week, the sixth annual Global Health Research Showcase proved that Global Health majors truly represent global interests.

This past summer, Duke PhD student Tulika Singh explored complementary diagnosis techniques for Zika virus pregnant women in Vitoria, Brazil. Zika is difficult to diagnose “because the PCR-based test can only tell if you’ve had Zika virus within about ten days of the infection,” Singh said. “That’s a big problem for enrolling pregnant women into our study on Zika transmission and maternal immunity.”

To combat this issue, Singh and her thesis advisor Sallie Permar trained collaborators to use the whole virion ELISA (WVE) laboratory technique which may reveal if an individual has been exposed to Zika. ELISA detects Zika through testing for the antibodies that most likely would have been produced during a Zika infection. Singh’s work allows the research team to better assess whether women have been exposed to Zika virus during pregnancy, and will ultimately guide Zika vaccine design. 

Master of Science in Global Health candidate Carissa Novak examined why some HPV positive women in Western Kenya are not seeking preventive measures against cervical cancer. All the women diagnosed with HPV were referred to the Country Hospital but only “33 to 42 percent actually sought treatment” leading to Novak’s main research question, “Why did so few women seek treatment?” To answer this question, she sent out quantitative questionnaires to 100 women and then followed up by interviewing 20 of them. She surveyed and interviewed both women who had and had not sought treatment. Her results showed that transportation and cost hinder treatment acquirement and that the women who did seek treatment were often directed to by a health worker or actively trying to prevent cervical cancer. Novak believes that increasing women’s trust and understanding of the health care system will assist in improving the percentage who seek treatment.

In Kunshan, China, Brian Grasso evaluated the development of Kunshan’s health system in relation to its economic development. “Kunshan is now China’s richest county-level city and it used to be a small farm town…My main take away was that economic growth has strengthened Kunshan’s health systems while also creating new health challenges,” Grasso said. What are some of these new health challenges? Some of them include air pollution, increased stress in manufacturing jobs and more car accidents. Grasso determines that other developing health systems should learn from Kunshan that without proper regulations poor health can result in the midst of progress.

Post by Lydia Goff

New Blogger Lydia Goff: Freshman with a Passion for Science Communication

Hey! My name is Lydia Goff. I am a first-year at Duke and plan to double major in English and biology in order to pursue a career in science writing. I was born in Waukesha, Wisconsin but raised primarily in the Charlotte area. My junior year of high school I transitioned from homeschool to Gaston Day School where I developed my interest in scientific research. Neither of my parents attended college so my primary teachers were books. Homeschooling instilled my love of reading which grew into an interest in writing, but it also limited my resources.

I had no exposure to scientific research until my junior year at Gaston Day when I became involved in the International Genetically Engineered Machine (iGEM) team. We worked on genetically engineering E. coli K12 so that it would die if accidentally released into the environment through a process called a kill switch. Particularly in developing countries with restricted supplies, improper disposal of genetically engineered bacteria can lead to water supply contamination. Working with my team and amazing faculty mentor showed me not only how interesting scientific research is, but also the global benefits.

A smiling woman

Lydia Goff in front of Baldwin Auditorium.

In iGEM, I ended up taking the lead in communications. Many of my teammates could understand and perform scientific procedures with a remarkable skill but struggled to communicate their ideas. I love being able to discuss the passions of others. These interactions allow me to continuously learn and to help others express themselves. Until that leadership role in iGEM, I was unsure about a major. I enjoyed writing and reading but also the STEM world. My interests bounced from calculus to creative writing to genetic engineering to art history. As I got older and the “What do you want to major in?” question became increasingly relevant, the idea of choosing one subject to focus on was painful. I did not want to stop learning about genetic engineering and neuroscience and astronomy in order to become a writer. For me, science writing and this blog represent the opportunity to never stop learning. They allow me to bounce around from lecture to laboratory and meet experts in a variety of fields, to discover the inspirations and implications of their research, and to express their ideas and discoveries to any curious person.

Post by Lydia Goff

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