Spring 2017 -- Conserving Our Future

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Carolina Scientific

scıentıfic Spring 2017 | Volume 9 | Issue 2

CONSERVING OUR FUTURE Coral reefs in decline— what it will take to protect them full story on page 34 1

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If you are interested, please contact carolina.scientific@gmail.com Find us on facebook facebook.com/CarolinaScientific Follow us on twitter @UNCSci Check out our blog carolinascientific.org

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scÄąentific Mission Statement: Founded in Spring 2008, Carolina Scientific serves to educate undergraduates by focusing on the exciting innovations in science and current research that are taking place at UNC-Chapel Hill. Carolina Scientific strives to provide a way for students to discover and express their knowledge of new scientific advances, to encourage students to explore and report on the latest scientific research at UNC-Chapel Hill, and to educate and inform readers while promoting interest in science and research.

Letter from the Editor: When the validitiy of the sciences is questioned, the accurate communication of research and its results becomes allimportant. For eight years, Carolina Scientific has endeavored to do just that—to clearly present research and broaden understandings. In this issue, we discuss ground-breaking research conducted at UNC-Chapel Hill. Read about a more measured perception of psychiatric disorders (page 16), the second that our universe began (page 24), and the best-selling drug that almost never was (page 36). We hope you enjoy!

- Ben Penley

on the cover Dr. John Bruno is a professor in the biology department at UNC-Chapel Hill.

His research seeks to uncover methods for conserving our coral reefs. Full story on page 34.

Painting by Julianne Yuziuk.

carolina_scientific@unc.edu carolinascientific.org facebook.com/CarolinaScientific @uncsci

Executive Board Editor-in-Chief Ben Penley Managing Editor Karthika Kandala Associate & Design Editor Ami Shiddapur Associate Editors Aakash Mehta Akshay Sankar Lynde Wangler Design Editor Nirja Sutaria Copy Editor Patrick Truesdell Treasurer Elizabeth Smith Publicity & Fundraising Chair Allie Piselli Online Content Manager Tirthna Badhiwala Faculty Advisor Gidi Shemer, Ph.D. Contributors Staff Writers Holly Bullis Richard Chen Haley Clapper Alexandra Corbett Kristi Dixon Sara Edwards Samuel Goldstein Patrick Gorman Jeremiah Hsu Hannah Jaggers Hannah Kim Grant Pieples Mackenzie Price Kevin Ruoff Emily Schein Zarin Tabassum Sophie Troyer Janet Yan Designers Alexandra Corbett Sydney Didonato Stephanie Dong Suhani Gupta Esther Kwon

Copy Staff Anna Arslan Alexandra Corbett Sara Edwards Jason Gershgorn Samuel Goldstein Patrick Gorman Marwan Hawari Jie He Alexander Payne Adesh Ranganna Bri Sikorski Wilfred Wong Illustrators Alexandra Corbett Stephanie Dong Isys Hennigar Rachel Howard Maddy Howell Tatihana Moreno Larissa Wood Julianne Yuziuk

This publication was funded at least in part by Student Fees which were appropriated and dispersed by the Student Government at UNC-Chapel Hill as well as the Carolina Parents Council.

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contents Life Sciences

Special Topics

6

Asking the Difficult Questions

28

Intelligent by Degrees

8

The World Inside Us

30

Out of the Loop

Diversifying the Roots of STEM

32

Viral Survival: Understanding How Viruses Evolve Host Shifts

10

Janet Yan

Sophie Troyer

Hannah Kim

Binge Drinking: Bad to the Brain

16

A Frontal Approach to Psychiatric Disorders

34

Health and Medicine

Learning to Love Your Anxiety Hannah Jaggers

Physical Science

20

String Theory: When Science Fiction Becomes Reality

Kevin Ruoff

22

A Probe Into the Beginning of Time

24

Shedding LITE: Optimization of the Light Sheet Microscope

Patrick Gorman

Richard Chen

26

Coral Reefs in Decline: What it Will Take to Save Them Sara Edwards

Emily Schein

Alexandra Corbett

18

Haley Clapper

Kristi Dixon

Neuroscience and Psychology

13

Holly Bullis

What’s on the Surface?

Mackenzie Price

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36

Scaling Down to Ramp Up

38

HIV Bounces Back

40

Shining the Spotlight on Zika

42

The Invisible Needle

Samuel Goldstein

Zarin Tabassum Grant Pieples

Jeremiah Hsu

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Illustration by Alexandra Corbett

ASKING THE DIFFICULT QUESTIONS: Monitoring and Evaluation

By Janet Yan

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any local and global organizations have become increasingly concerned with protecting the reproductive rights of women in developing nations. These institutions want to empower women to make their own decisions about when to have children by providing them access to suitable contraceptive methods. Studying this phenomenon by conducting research and implementing programs has the potential to improve the lives of women and to strengthen communities. However, because resources and funding are often limited, it is crucial for researchers to determine whether or not said programs are effective in the long-run. Dr. Ilene Speizer, a professor in the Department of Maternal and Child Health (MCH) at UNC-Chapel Hill and a faculty fellow at the Carolina Population Center, is conducting research to explore these concerns. By working with program implementers and analyzing data, Dr. Speizer is asking the difficult questions

necessary to help advance and improve family planning and MCH programs abroad.

Dr. Speizer’s interest in public health began during the time she spent in Togo (a small Francophone country in Western Africa) while serving in the Peace Corps. Several of her local friends were young women who had unintentionally gotten pregnant, and as a result, had to set aside their career ambitions in order to

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Dr. Ilene S. Speizer

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the variables of interest directly. In an ideal world, a randomized controlled trial (RCT) would be the strongest study design, allowing researchers to randomize subjects into groups

care for their children. Through these interactions, Dr. Speizer realized that she wanted to help these women “get family planning when they needed it” in order to aid them in achieving their dreams.1 Furthermore, she chose to contribute to the monitoring and evaluation (M&E) research of global public health programs.

Dr. Speizer works with prominent organizations such as FHI360 and IntraHealth, both of which are based in the Triangle, to evaluate the effectiveness and sustainability of family planning and MCH programs. Her main project, funded by the Bill and Melinda Gates Foundation, is the Measurement, Learning & Evaluation (MLE) project, “which is the evaluation component of the Urban Reproductive Health Initiative, a multi-country program in India, Kenya, Nigeria, and Senegal… that aims to improve the health of the urban poor.”2 Oftentimes, the importance of evaluation programs in the field of public health is underappreciated, as many organizations tend to focus on implementation and shy away from data and evidence in fear that it may incite doubt around the usefulness of their programs. For example, in recent years, the fields of cancer biology and psychology research have been under scrutiny for the irreproducibility of many key studies.3 As a result, unnecessary effort has been put into reproducing their original findings. In the field of public health, evaluating the impact and sustainability of programs is the same as affirming the reproducibility of results and the utility of limited funding. Dr. Speizer and her team are trying to determine whether these programs are actually affecting the intended populations and whether they will succeed when implemented on a larger scale.

Figure 1. Dr. Speizer and a worker in a Patent Medicine Seller (drug shop) in Abuja, Nigeria. Photo courtesy of Dr. Speizer. and control for variables that could affect the outcome of interest. However, in the real world, and especially in the field of public health, RCTs are nearly impossible. One solution to this problem is the use of longitudinal data collection, which involves “following the same women over time so that by having a baseline before the program [starts], we know what their characteristics are and their prior family planning used experience and motivations.”1 This method comes with the risk of not being able to find the women as time passes, especially in complex urban environments like Nairobi, Kenya. Consequently, Dr. Speizer said “a lot of it is working with what you have and strategizing from the beginning.”1 Looking forward, Dr. Speizer will be exploring program scale-up: how to implement a program into a larger population while retaining its effectiveness. Additionally, she is also moving towards examining the sustainability of programs. “So what if the use and quality of care increased, what happens when the donor leaves? If [the positive results] go away, what are we using our resources for?”1 She will undertake this study in Nigeria by examining two cities: one in which a program continues to operate, and one whose program ends. Dr. Speizer hopes to study family planning and MCH programs more closely to ensure that women receive the best opportunities and care possible.

“So what if the use and quality of care increased, what happens when the donor leaves?”

Dr. Speizer’s work in evaluation involves close collaboration with the implementing organizations, “[meeting] with them at all phases,” sharing their findings at baseline, midterm, endline, and in between, so they can “adapt their programs based on what [the evaluators] learned.”1 Determining the effectiveness of an intervention is essential, but it is just as necessary for researchers to take this information and apply it to improve the intervention. Dr. Speizer and her team’s responsibilities include “[building] organizations’ capacities to understand data...and [using] data to inform their programs.”1 Evidence-based decision-making encourages organizations to turn good ideas into effective and well-considered programs.

By working closely with the implementing organization on study design, Dr. Speizer is able to integrate necessary elements into the design of a program by using statistical and modeling methods to analyze data. As with many research projects, she encounters barriers that make it difficult to study

References

1.Interview with Ilene Speizer, Ph.D. 02/13/17.

2.Measurement, Learning, and Evaluation Project for the Urban Reproductive Health Initiative. https://www.urbanreproductivehealth.org/. (Accessed February 15th, 2017).

3.Baker, Monya. 1,500 Scientists Lift the Lid on Reproducibility. http://www.nature.com/news/1-500-scientists-liftthe-lid-on-reproducibility-1.19970. (Accessed February 27th, 2017).

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The World Inside Us:

Illustration by Rachel Howard

The Importance of the Microbiome in the Future of Medicine

By Sophie Troyer

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and other resources limit bacterial growth, so the normal bacteria that already have a symbiotic relationship with the human body maintain control of that area. In the intestines, for example, there is a relatively large amount of bacteria which aid in digestive processes.

On May 12, 2016, the White House announced the National Microbiome Initiative, reaffirming the importance of understanding the microbes that play an import role in the world. The goal is to promote the collaborative study of microbiomes in different ecosystems.1 In accordance with this initiative, over $121 million was set aside for microbiome studies across ecosystems.1 UNC-Chapel Hill is investing $4.9 million into interdisciplinary microbiome research.2 This initiative, and the push that UNC is bringing to the project, serves to unite researchers in different areas to focus on the larger goal of understanding the microbiome.

The Microbiome Core Facility, established in 2009, is unique in that it provides microbiome research support from the experimental design to data analysis.3 Dr. Andrea Azcarate-Peril, the facility’s director and an assistant professor of Medicine at UNC, said that there has already been a large shift in the understanding of the role of the microbiota in human health within the last 10 years.4 Scientists are beginning to understand how humans impact their own microbiota and how this impacts their health. There has also been a change in the approach used to study microbial communities. For instance, the development of next generation sequencing has significantly improved scientists’ ability to study the microbiome.

Before, it was hard to study complex microbial populations.

Sequencing has made this easier.4 Dr. Azcarate-Peril has studied probiotics and prebiotics for over 20 years.4 Probiotics are bacteria that can help the digestive system, and prebiotics can promote the growth of

he human body hosts a wide range of microorganisms, many of which are a part of normal bodily function. The human microbiota is composed of all the microbes in and on a human body, which include bacteria, fungi, and viruses. Although the bacteria in human bodies are normally balanced, this balance can be disturbed by antibiotics or drastic changes in diet. Probiotics and prebiotics are often marketed to balance the microbiota, particularly in the intestinal tract. Scientists studying the microbiome are interested in developing medicine tailored to maintaining a healthy and desirable microbiota.

The normal human microbiota forms a barrier against invading pathogens. Since the surfaces of the human body are covered with symbiotic bacteria, there is competition for resources, and it is unlikely that a new strain of bacteria could find a niche to grow on an already populated surface. Space

(Left) Dr. M. Andrea Azcarate-Peril (Right) Dr. Ryan Balfour Sartor

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options, as opposed to treatments that suppress the immune system.5 A healthy gut bacteria population can promote better health overall, as it can impact inflammation, metabolic syndromes, diabetes, and obesity.5 UNC is already recognized for its leadership in researching the role of gut bacteria in intestinal inflammation.5 The gnotobiotic facility has also received wide recognition.5 There is still a lot of progress to be made, and UNC is positioned to play an important role in fulfilling the goals of the White House Microbiome Initiative. Both Dr. Sartor and Dr. AzcaratePeril agreed that the initiative largely affirms the importance of research on the microbiome.4,5 Dr. Sartor also stressed that the initiative will spur integration between other areas of biology on the topic of the microbiome, which has not happened yet.5 Research into the microbiome will open doors to an entire field of medicine that is largely unexplored.

probiotic bacteria. The question is which specific probiotics and prebiotics are most helpful to the digestive system, and how this varies between individuals. Previously, researchers like Dr. Azcarate-Peril studied isolated bacteria in pure cultures (where only one strain of bacteria is present); now, researchers are able to analyze entire communities. This allows scientists to assess the impact of a bacterial species within the community, including how they communicate with other microorgan-

"A greater understanding of the bacteria within human bodies can lead to methods to correct bacterial composition or function. These methods can be better, less toxic, treatment options..."

References

1.Fact sheet: Announcing the Microbiome Initiative. https://obamawhitehouse.archives.gov/the-press-office/2016/05/12/fact-sheet-announcing-national-microbiome-initiative (Accessed February 17, 2017).

2.Fact sheet: Announcing the Microbiome Initiative. https://obamawhitehouse.archives.gov/sites/whitehouse. gov/files/documents/OSTP%20National%20Microbiome%20Initiative%20Fact%20Sheet.pdf (Accessed February 17, 2017).

3.Maximizing Microbiome Knowledge. http://research. unc.edu/2016/05/13/maximizing-microbiome-knowledge/ (Accessed February 17, 2017).

4.Interview with M. Andrea Azcarate-Peril, Ph.D. 09/30/16.

5.Interview with Ryan Balfour Sartor, Ph.D. 09/30/16.

isms and with the host. In the near future, Dr. Azcarate-Peril believes that it will be necessary to study pure cultures again and then go back to communities in order to understand bacterial interactions and the role of specific strains.4 So, how do probiotics play a role in human health?

99.9% of the microbes in human bodies are beneficial. People are starting to realize that the overuse of antibiotics is detrimental to health and should be avoided with children. A number of autoimmune diseases are actually caused by oversanitization. This is something that people have the power to control. As Dr. Azcarate-Peril said: “We need to become more conscious about our surrounding microbes.”4 UNC researchers are working to understand these surrounding microbes in order to prevent disorders caused by an unhealthy microbial composition in the body. Dr. Ryan Balfour Sartor, director of UNC’s Multidisciplinary Inflammatory Bowel Diseases Center, hopes to develop better patient care as a result of this research.3 He noted that the White House Microbiome Initiative has great value in pulling people together from different areas of biology, all of whom contribute different perspectives.5 Dr. Sartor investigates how gut bacteria interacts with the host’s immune response, including bacterial impact on epithelial cells. He runs a gnotobiotic rodent facility, which has mice that have not been colonized by bacteria, fungi, or viruses. This facility enables researchers to compare the physiology and pathophysiology of mice that have varying bacterial exposure. This means researchers can see whether a specific microbe has an impact on the health of the mouse. Currently, Dr. Sartor is working on manipulating gut bacteria to see how it affects inflammation. In genetically susceptible hosts, bacteria can cause inflammation. Sometimes people can have chronic inflammation or an autoimmune disease as a result. Because of this, it is important to understand how normal gut bacteria can maintain human health, including normal immune function and digestion.5 A greater understanding of the bacteria within human bodies can lead to methods to correct bacterial composition or function. These methods can be better, less toxic, treatment

Illustration by Larissa Wood

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Illustration by Larissa Wood

Diversifying the Roots of STEM

BY HANNAH KIM

T

hink of a famous scientist. Albert Einstein might come to mind. Maybe Newton, Darwin, or Edison. If you think hard enough, you might remember Marie Curie or Rosalind Franklin. Without a doubt, it is difficult to name groundbreaking scientists who are not white males. This is not a trend restricted to scientific history from hundreds of years ago; a lack of diversity continues to limit the kind of representation seen today in scientific development and research. A recent study conducted by the National Science Foundation found that white males account for 51% of the STEM workforce, while they make up less than 32% of the general US population (Figure 1).1 Simply put, it is harder for one to identify as a scientist and see oneself as part of the scientific community when fellow scientists are predominantly of a race, gender, sexuality, socioeconomic background, or other identity to which you do not belong.

This issue inspired Chancellor Folt and the science faculty at UNC-Chapel Hill to create the Chancellor’s Science Scholars program (CSS), dedicated “to the advancement of groups that have traditionally been underrepresented in science, technology, and math disciplines.”2 Program Coordinator Dr. Richard Watkins reflected on the incredible extent of the issues the program attempts to overcome: “I think there’s a cliché term that goes, ‘It’s easier said than done.’ There are centuries of historic factors and influences that have prevented diversity from being included in STEM.”3 Through the perseverance of program leaders, combined with the drive of its

Chancellor’s Science Scholars Cohort 4.

Courtesy of Samantha DeVelbiss students, the program seeks to create an unstoppable force of innovation and compassion in science.

The CSS program is a science scholarship program, with strong emphasis on the true meaning of scholarship over the financial incentive. While a monetary scholarship is crucial, especially for the many accepted students of low socioeconomic backgrounds, it is the curriculum that sets it apart from many other scholarship programs on campus. Essential to CSS is a unique summer program called the Summer EX-

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ate and professional programs. CSS leadership works closely with Meyerhoff and similar programs, such as the Millennium Scholars at Penn State, to share knowledge and progress with one another. Not only do the program directors stay in regular contact, but the scholars of each program also interact early on. A key aspect of the Summer EXCELerator program, modeled after Meyerhoff’s Summer Bridge, is a weekend where incoming cohorts of CSS, Meyerhoff, and Millennium scholars come together at UMBC to share their experiences and network with students around the country who share similar interests.

Despite the fact that the program is relatively new, research conducted by the UNC Department of Psychology and Neuroscience already demonstrates its success in achieving its mission. An analysis of CSS participants and a comparison “science interested” UNC student group found that both the mean first-year overall GPA and science GPA of CSS students were significantly higher than those of the comparison group.4 The CSS program appears to positively affect scholars’ performance throughout their undergraduate years, but as the program matures and the first students graduate this semester, the department will continue to conduct research on its efficacy. Considering that the model program of the UMBC Meyerhoff Scholars has been incredibly successful, CSS looks to follow in its sister program’s footsteps.

“The program directors have really associated people into labs,” said Snigdha Das, a CSS scholar who conducts research in computational fluid dynamics through the UNC School of Medicine. “[Their extensive connections] within the science departments have allowed [CSS Scholars] to start working first semester as freshmen.” 5 Das explores the differences in drug particle deposition between individuals of different ethnicities, with the aim of improving the drug efficacy.

Her personal appreciation for diversity, coupled with the social and academic support of CSS, have enabled her to fully immerse herself in research regarding what makes people of different racial backgrounds react differently to different methods of drug delivery.

Figure 1: Science and Engineering Workforce vs General US Population. Courtesy of ThinkProgress, Data from NSF Women, Minorities, and Persons with Disabilities in Science and Engineering Digest, 2015.

CELerator, where members of the incoming first-year cohort live and learn together for an intensive six weeks. Through this summer experience, students get a head start on coursework and familiarize themselves with UNC’s extensive resources.

All scholars take workshops on diversity and science and receive credit for coursework in communications, mathematics, and research. The EXCELerator introduces the workload, time management, and interpersonal connections that are essential for a career in scientific research. Although CSS requires all of its scholars to meet rigorous academic standards throughout their undergraduate years, the Summer EXCELerator provides the solid foundation for success in these endeavors before their first semester even begins.

The impact and responsibility that comes with the CSS program certainly surpasses that of many other scholarships, but it is not the first of its kind. The Chancellor’s Science Scholars is modeled after the Meyerhoff Scholars of the University of Maryland, Baltimore County (UMBC). This incredibly successful program has produced over 1,000 alumni, hundreds of which have completed or are currently enrolled in gradu-

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“Without a doubt, it is difficult to name ground-breaking scientists who are not white males.”

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Dr. Mike Crimmins, Executive Director of Chancellor’s Science Scholars Program.

Courtesy of UNC-CSS Website.

Dr. Noelle Romero, UNC-PROPS Program Coordinator. Courtsey of UNC-CSS Website.

Dr. Richard Watkins, Program Coordinator of Chancellor’s Science Scholars.

Courtesy of UNC-CSS Website.

Both students and staff expect to see CSS expand exponentially in the future. Program Coordinator Dr. Noelle Romero said, “I expect our scholars to change the world…The program itself, hopefully it’s going to be here for years and it’s going to be a staple of UNC, and a shining gem, as Carolina tradition would have us say.”3 As the program recruits its fifth cohort and graduates its first group of students, it looks to be the beginning of a powerful legacy.

“Despite the fact that the program is relatively new, research conducted by the UNC Department of Psychology and Neuroscience already demonstrates its success in achieving its mission.”

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References

Dr. Samantha DeVilbiss, UNC-CSS Program Coordinator for First-Year Students. Courtesy of UNC-CSS Website.

1. Raymond, L. National Science Foundation Launches Million-Dollar Initiative To Improve Diversity in STEM. Retrieved from https://thinkprogress.org/national-sciencefoundation-launches-million-dollar-initiative-to-improvediversity-in-stem-3f2f4183d3e#.n8xwm6h7t (Accessed February 26, 2016).

2. Chancellor’s Science Scholars. Web. (n.d.). Retrieved from http://chancellorssciencescholars.web.unc.edu/ 3. Interview with Noelle Romero, Ph.D., Richard Watkins, Ph.D., and Samantha DeVilbiss, Ph.D. 02/13/17.

4. Greifer, N.; Sathy, V.; Panter, A. Evaluating UNC’s Chancellor’s Science Scholars Program: Early Academic Outcomes. The University of North Carolina at Chapel Hill Department of Psychology and Neuroscience 2016.

5. Interview with Snigdha Das. 02/13/17.

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neuroscience and psychology

Illustration by Maddy Howell

Binge Drinking: Bad to the Brain

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eer pong, drinking games, taking shots—these are all ways that students unwind from a rigorous week at Carolina. But, are these seemingly harmless festivities to relieve stress having a negative effect on your brain?

Binge drinking is a common behavior among college students, but many do not fully realize the adverse effects this activity has on your brain’s chemical balance. Dr. Todd Thiele of the Behavioral and Integrative Neuroscience Program in the Department of Psychology and Neuroscience at UNC-Chapel Hill stud-

By Emily Schein

ies the brain mechanisms that modulate excessive binge drinking.

Binge drinking can be defined as drinking enough to raise your blood alcohol concentration (BAC) to >0.08% in 2-4 hours.1 As you can imagine, this is common behavior for a night out. What most students do not consider is that this behavior can lead to becoming dependent on alcohol and could eventually lead to serious substance abuse problems.1 Dr. Thiele uses a mouse model to study the chemicals called neuropeptides, a type of neurotransmitter, that

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Dr. Todd Thiele

neuroscience and psychology control binge drinking (Figure 1). These neuropeptides are located in regions of the brain that also control emotional behavior. Binge drinking causes a change

occur when the mouse models binge drink, allowing him to study the chemical changes in the brain.

The Thiele lab uses this infor-

“Binge Drinking is a common behavior among college students, but many do not fully realize the adverse effects this has on your brain’s chemical balance.” in neuropeptide levels, causing them to be deregulated in these areas of the brain. Dr. Thiele explained how this can lead to a dangerous cycle: “These alterations in this brain neuropeptide system with repeated binge drinking causes people to want to continue to binge drink, and then you have this vicious cycle where people start to become dependent and if they continue on, ultimately begin to lose complete control of their drinking.”1 Dr. Thiele and his lab hope to understand these neuropeptide systems better, so that a treatment can eventually be found to protect people from becoming dependent on alcohol.

Dr. Thiele started his research during graduate school in the mid-90s. Ever since, he has been intrigued by the neuromechanisms behind alcohol dependence and how it shapes the chemical systems in the brain. The Thiele lab uses mice and a technique called immunohistochemistry (IHC) (Figure 2), which allows certain chemicals, in this case neuropeptides, to be tagged and traced. Dr. Thiele uses this method to monitor rising and falling neuropeptide levels that

mation to study systems that could influence binge drinking. Dr. Thiele explained how he uses “pharmacological approaches” which involve using “compounds that are receptor agonists or antagonists for these neuropeptide systems that we study.”1 Using these receptors, Dr. Thiele has found that “sometimes [they] can cause binge drinking to go down and this implicates these systems in modulating binge drinking.”1 An important neuropeptide sys-

mine (another neurotransmitter) which aids in pleasure and reward. Because these areas are heavily involved in emotions, this leads to feelings of “liking” and “wanting” alcohol. These raised CRF levels cause binge-like drinking behavior and CRF levels are also increased by binge drinking.2 This leads to a constant loop of dangerous behavior. By using this information, Dr. Thiele can find ways to modulate this system, and other systems involved in binge drinking, to break the loop. By zeroing-in on certain neuropeptide systems, the Thiele lab can take progressive steps in finding a treatment that may help reduce excessive alcohol drinking.

Dr. Thiele was very optimistic when talking about finding potential treatment. He spoke of “cutting-edge technology” that he uses in his lab called chemogenetics, which allows a researcher to “manipulate the activity of specific chemical systems in the brain.”1

“By zeroing in on certain neuropeptide systems, the Thiele lab can take progressive steps in finding a treatment that may help reduce excessive alcohol drinking.” tem that regulates binge drinking is corticotropin-releasing factor (CRF). It has been shown that CRF protein levels were significantly increased in the amygdala and ventral tegmental area after binge drinking (Figure 3).2 The amygdala modulates emotions, and the ventral tegmental area produces dopa-

Figure 1. A common neuropeptide structure.

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Using genetically altered receptors, chemogenetics enables Dr. Thiele to turn on or turn off specific neurons and identify potential targets that influence binge drinking.1 This new approach has led to exciting leaps. For the past ten years, Dr. Thiele and his colleagues have studied a neuropeptide system known as mela-

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Figure 2. A slice from the brain of a mouse stained by immunohistochemistry.

Image courtsesy of Wikepedia Commons.

neuroscience and psychology -nocortins, which have been shown to modulate binge drinking. Recently, evidence has emerged indicating that the drug, Buproprion, can activate the melanocortin system.1 Dr. Thiele is hopeful that this could lead to a potential pharmaceutical treatment.

Recently, Dr. Thiele and his colleague Dr. Montserrat Navarro formed a translational collaboration with Dr. JC Garbutt, a psychiatrist in the Medical School at UNC. They received a grant to start clinical trials in humans using Buproprion to see if it will be protective against excessive binge drinking.

Dr. Thiele spoke very excitedly about this new advancement: “We are getting close! We are taking what we discovered in animal models and applying this knowledge to potentially finding a new treatment for humans exhibiting reckless drinking behavior.”1 This is an excellent step in applying his research to humans and moving towards his goal of finding better ways to treat alcohol use disorders.

As a professor at UNC, Dr. Thiele is very passionate about his work and enjoys spreading knowledge about his lab and his research to the student body.

He realizes alcohol use disorders are a large problem for those in college and beyond, and he hopes that his research can ultimately save lives.1 Dr. Thiele has made encouraging progress and will continue to work towards finding treatments to protect people from alcohol dependence.

References

1.Interview with Todd Thiele, Ph.D. 02/14/2017.

2.Rinker, J.A.; Marshall, A.; Mazzone, C.M.; Lowery-Gionta, E.G.; Gulati, V.; Pleil, K.E.; Kash, T.L.; Navarro, M.; Thiele, T.E. Biol. Psychiatry. 2016, 1-10.

Figure 3. Neurons in the brain region called the “bed nucleus of the stria terminals”. These neurons produce CRF.

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neuroscience and psychology

A Frontal Approach to Psychiatric Disorders

By Alexandra Corbett Illustration by Alexandra Corbett

U

nfortunately, most people know someone who refuses to take mental health seriously. Whether this is a relative who sees mental health problems as being within the control of the patient, or a peer who views them as a matter of personality, blaming the patient is not an uncommon attitude. Dr. Aysenil Belger, a cognitive neuroscientist and professor of psychiatry and psychology at UNC-Chapel Hill, is currently working on research that combats these stereotypes and misconceptions and explores the neurobiological substrates of mental illness.

Dr. Belger’s research focuses on a variety of mental health problems, including schizophrenia, autism, post-traumatic stress disorder, and psychosis. The sample group she

Figure 1: The human brain. Courtesy of Photos for Class, Creative Commons.

uses for her research is composed of adolescents, aged nine to sixteen. The members of the study group either do not come from families with a history of neuropsychiatric disorders, or have a close family member with a psychotic disorder and are therefore considered to have an elevated risk for developing the same kinds of disorders.

Dr. Aysenil Belger Dr. Belger and her colleagues use a variety of methods to observe how the brains of patients with a familial risk for these disorders differ from those of participants without risk. One of the main methods used is known as an oddball test, which is “one of the oldest and most established paradigms for looking at the detection of a signal in a change in the environment.”1 Oddball tests vary in which senses they target—most often either visual or auditory—but their consistency is in how they stimulate the brain.2 For example, during an auditory oddball test, the patient listens to the same sound continuously repeated, often repeated beeping, while a second novel sound, differing in pitch, frequency, duration, amplitude, or volume, randomly occurs in the series. During these tests, the brain recognizes a pattern in the consistency of the beeps, and it begins to expect that the next sound will be the same as the last. When the patient hears the rare sound instead of the one their brain expected, the sensory mapping areas and the higher cognitive areas in the frontal cortex of the brain detect this change automatically.1 Using an EEG, this

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Carolina Scientific test allows neuroscientists to map how the brains of patients who suffer neurological disorders respond to changes and stimuli in the environment compared to the brains of patients with no history of mental health problems.2 Another kind of testing Dr. Belger’s research uses is a stressor test. During these tests, an MRI or EEG records brain activity. MRIs produce images of the brain that are sensitive to blood flow and blood oxygen levels, allowing neuroscientists to observe how different parts of the brain are activated during a cognitive activity.1 On the other hand, EEGs detect “low intensity electrical pulses coming from the brain,” which allow neuroscientists to determine not only whether the brain is being activated during cognitive tasks, but also how strongly it is being activated.1 EEGs further inform researchers about the temporal dynamics, intensity, and spatial distribution of activation in the brain. During these tests, neuroscientists use a psychological stressor to stimulate the brain. Dr. Belger uses two main sources of stress in her research. In the first, the patients are asked to answer a series of math questions by pressing buttons while lying in the MRI scanner. They are then given feedback on their performance that shows that they are doing worse than their peers. The second involves the patient telling a story that they have only minutes to concoct, and then being judged by an audience. This is conducted in two separate sessions, once during the MRI session and once

"This research on how the brains of schizophrenia patients function has stimulated a shift in the way that psychologists and psychiatrists approach schizophrenia." while wearing the EEG cap of electrodes. While the majority of the comparisons are done before and after the stressor, brain activity during the stressor is also noted. The goal of this research is to gain an understanding of how stress affects cognitive functioning in adolescents, and to determine whether stress-sensitivity can be correlated with the severity of clinical mental health symptoms.

From her previous studies, Dr. Belger has detected a clear decline in the activation in the frontal and limbic regions of patients with schizophrenia.1 This is corroborated by other research that shows that patients with schizophrenia have an abnormally low detection of visual and auditory events.2,3 Similar results have been found in patients with post-traumatic stress disorder and autism. This research on how the brains of schizophrenia patients function has stimulated a shift in the way that psychologists and psychiatrists approach schizophrenia.

Previously, schizophrenia was divided into categories, including catatonic, paranoid, disorganized, residual, and undifferentiated schizophrenia.4 However, neuroscientists now realize that there is a flaw in the way these categories are divided, as many of the symptoms occur in other psychotic disorders as well. Instead of grouping symptoms together under differ-

neuroscience and psychology

ent categories— many of which share common symptoms—neuroscientists are now breaking them down according to individual categories of symptoms and examining the neurobiological substrates of each symptom. Positive Figure 2: Activation of regions in the symptoms (attri- brain. Courtesy of Dr. Belger. butes someone with schizophrenia has that someone without schizophrenia would not) include hallucinations, delusions, and paranoia.

Dr. Belger and her colleagues focus primarily on the negative symptoms (attributes that someone with schizophrenia lacks that someone without schizophrenia has) associated with schizophrenia.1 They split the negative symptoms into five categories to study (flat affect, alogia, asociality/anhedonia, avolition/apathy, and attention), which allows them to look for the neurobiological causes of each individual symptom rather than looking for the causes of an entire group of symptoms.2 Dr. Belger hopes that her research will lead to the discovery of new and more effective ways to help people who suffer from neuropsychiatric disorders and helpw prevent the onset of these disorders in people who are at risk for developing them. With new technological developments in the field of neuroscience, researchers like Dr. Belger can anticipate being able to take their work from the lab and into the field in patients’ day to day lives. Mobile EEGs may one day allow researchers to monitor patients’ brain activity as they go about their daily lives in their “natural” environment, affording valuable information that is unaffected by the artificiality of the lab setting. With any luck, some of Dr. Belger’s research can be used to create a shift in the attitude about mental health and support the view that rather than being a product of personal flaws, mental health is dependent upon a multitude of neurological factors and the functioning of the body’s most complex organ.

References

1. Interview with Aysenil Belger, Ph.D. 02/07/17.

2. Shaffer, J. J. et al. Mol. Neuropsychiatry. 2015, 1(4), 191200.

3. Hart, S. J.; Bizzell, J.; Mcmahon, M. A.; Gu, H.; Perkins, D. O.; Belger, A. Psychiatry Res. Neuroimaging. 2013, 212(1), 19-27.

4. Are There Different Types of Schizophrenia? (n.d.).

Retrieved March 11, 2017, from http://www.webmd.com/ schizophrenia/guide/schizophrenia-types

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neuroscience and psychology

Learning to Love Your Anxiety

By Hannah Jaggers Illustration by Maddy Howell

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weaty palms, a racing heart, uncontrollable shaking, nausea, and dizziness: all uncomfortable sensations associated with anxiety. While people with anxiety often try to avoid these symptoms, some researchers believe that becoming comfortable with the uncomfortable could be the real key to overcoming anxiety.

Dr. Jonathan Abramowitz Dr. Jonathan Abramowitz, a UNC-Chapel Hill researcher and professor in the Department of Psychology and Neuroscience, studies the nature and treatment of obsessive-compulsive disorder (OCD) and other anxiety disorders. His research focuses on new treatments for these disorders that alter the way traditional exposure therapy is performed to promote the acceptance, rather than the elimination, of anxiety.

OCD is characterized by two features: obsessions, which are intrusive thoughts that evoke anxiety, and compulsions, which are behaviors performed to reduce this anxiety.1 Dr. Abramowitz studies the effectiveness of an OCD treatment called exposure and response prevention (ERP). The exposure component of this therapy works by helping patients confront their obsessional fears. The response prevention element of ERP urges patients to refrain from engaging in compulsive rituals and behaviors that a person with OCD would normally engage in to reduce anxiety levels. Historically, psychologists

believed that exposure therapy worked through a process of fear habituation. In this process, patients gradually display less anxiety to a fearful stimulus as it is repeatedly presented.

However, current research has shown that fear habituation is not equivalent to learning that obsessional fears are not harmful.1 In fact, Dr. Abramowitz stated that successful treatment of OCD using exposure therapy can occur even in the absence of habituation, and that an overreliance on habituation can sometimes result in the patient experiencing a “return of fear” after exposure.2 This return of fear occurs when patients revert back to previous, high anxiety levels when presented with the fearful stimulus.1 A new approach to OCD treatment that Dr. Abramowitz employs is called inhibitory learning theory. This theory suggests that exposure therapy works to reduce fear not by disrupting fearful responses through habituation, but by introducing new non-threat associations that compete for retrieval when a person is presented with a fearful stimulus. Research has shown that inhibitory learning might be more effective in long-term reduction of fear and in reducing the return of fear.1 While Dr. Abramowitz recognizes that ERP is the best form of therapy for anxiety disorders, he believes that old methods can always be improved. He wonders: “How can we do even better than we’ve been doing?”2 Additionally, Dr. Abramowitz does not advocate for the complete elimination of fear during ERP sessions. He explains that doing so implies that anxiety itself is fundamentally destructive and this can lead to patients developing a “fear of fear.”2 Rather than relying on habituation of anxiety as a marker for treatment success, Dr. Abramowitz encourages his patients to completely alter their concept of anxiety. “What we want is to help people become better at having anxiety, not

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Carolina Scientific better at making anxiety go away. After all, anxiety is not dangerous.”2 Dr. Abramowitz’s research team has focused on how the acceptance and tolerance of fear can lead to better longterm outcomes for people with OCD and reduced instances of the return of fear. Acceptance and commitment therapy (ACT) promotes the idea of fear tolerance and encourages patients to find a willingness to experience unwanted anxious feelings during exposure therapy instead of teaching patients to “fix” or eliminate their fear or anxiety.1 Dr. Abramowitz’s team recently finished a study testing the effectiveness of ACT used in conjunction with ERP as an OCD treatment.

Through his research, Dr. Abramowitz wants to reinforce the idea that anxiety is not something abnormal or something to be suppressed. “We start from the idea that everyone has anxiety,” Dr. Abramowitz stated.2 “We need it. It serves a purpose—to protect us from harm and to help us do our best when under pressure. Why would you want to do a therapy to make it go away?”2 Dr. Abramowitz believes that the better solution is to teach people how to be okay with their anxiety whenever it shows up in their lives. By testing the effects of both ACT and inhibitory learning used with exposure therapy, Dr. Abramowitz hopes to develop a treatment for anxiety disorders that is effective for everyone. This is a challenging task, considering many people find exposure therapy too intolerable due to the anxiety it induces. According to Dr. Abramowitz, ACT can help make exposure therapy more palatable by giving the treatment a better rationale.2 Dr. Abramowitz explained: “In the long run, they have to lean into it and say ‘I know this is uncomfortable, but it’s only anxiety.’”2 In his treatments, Dr. Abramowitz also addresses the fear of uncertainty that people with OCD face.

These uncertainties can be long-term, like questioning the afterlife, or more short-term, like wondering if not washing one’s hands now will result in the immediate contraction of a disease. While people with OCD struggle more with accepting these uncertainties in their lives, Dr. Abramowitz stresses that “the uncertainty that a person with OCD has is no different than the uncertainty that anyone else has. What we’re helping them do is to just confront their everyday level of uncertainty that they’re afraid to think about.”2 Dr. Abramowitz believes that there is a stigma about anxiety disorders that stems from people not realizing that these problems exist on a continuum with non-clinical and everyday life experiences. “The DSM (Diagnostic and Statistical Manual of Mental Disorders) wants the world to believe that these are medical diseases and that there is an objective or biological cutoff between having a disorder and not having it,”

neuroscience and psychology

Figure 1. Anxiety disorders are the most common psychological complaint. Photo by Rabih. Image courtesy of Flickr Creative Commons.

Dr. Abramowitz recounted.2 “That is a flawed view which is not supported by research.”2 Likewise, Dr. Abramowitz wants people to realize that anxiety disorders cannot be explained by a single biological imbalance or by a traumatic history. While these factors can contribute, many elements are involved in the development and maintenance of anxiety disorders and many aspects of these problems are still unexplained. “Fortunately,” he said, “although we don’t yet know precisely what causes anxiety disorders, we do have effective psychological treatment approaches. Research shows that cognitive-behavioral therapy (CBT) can be highly effective, even without the need for medication.”

Through his research, Dr. Abramowitz hopes to change the negative way society looks at anxiety disorders. He believes that by reducing the stigma, people who suffer from anxiety disorders could learn to embrace rather than run away from the uncomfortable symptoms of anxiety. “Anxiety is uncomfortable, but it’s not dangerous. It doesn’t last. It’s like blinking or breathing. We need it to stay alive.”2

Through his research, Dr. Abramowitz wants to reinforce the idea that anxiety is not something abnormal or something to be suppressed.

References

1. Jacoby, R. J.; Abramowitz, J. S. Clinical Psychology Review.

2016, 49, 28-40.

2. Interview with Jonathan Abramowitz, Ph.D. 02/06/17.

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Figure 1. Solar Mass Falling into a Black Hole. Photo courtesy of NASA CC BYNC-ND 2.0.

physical science

String Theory: When Science Fiction Becomes Reality

By Kevin Ruoff

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cience fiction is becoming less fiction and more reality.

Physics research has been making strides to make the concept of multiple dimensions more than the subject of an action-packed thriller.

Dr. Jonathan Heckman, a researcher at UNC-Chapel Hill, is one of the few that can wrap his mind around the concept of string theory, something that breaks down every comfortable Dr. Jonathen Heckman notion of how the world works.

“How the world works” is physics in a nutshell. Modern physics can describe the world with the equations of Newton, Einstein, and Maxwell, among others. Their work established the concept of four fundamental forces that govern the world-most notably, gravity. These forces are explored in a multitude of equations that describe many of the processes in the universe. String theory is the attempt to unify everything we know into one simple theory. Dr. Heckman described string

theory as, despite what it may seem, the “simplest, most elegant answer to very complicated questions.”1 String theory is a field of study that concerns itself with thinking of the world as, as the name suggests, strings.

It posits that humans are made of strings, planets are made of strings, and even the physical concept of gravity is made up of strings. There are no particles, but rather fundamental strings that vibrate and move in distinct ways. Similar to how strings on a guitar are plucked differently corresponding to different musical notes, these fundamental strings are plucked in ways corresponding to the different fundamental particles, like protons and electrons. The basic principles of physics still apply, but with this idea there is no distinction between gravity and electromagnetism. The forces that govern black holes, nuclear physics, magnets, the auroras, and electricity are all one in the same.

String theory came about in an attempt to combine the two ways that physicists understand how things work. Physicists know how things work on a very large scale (gravity) and they know how things work on a very small scale (quantum mechanics). The two explanations do not seem to be compatible with one another. String theory was first introduced to explain the forces that hold nuclei together but turned out to be much more. To think about the world differently, the first string theorists replaced the notion of particles as point-like

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Carolina Scientific structures with something that was more spread out in the shape of a one-dimensional loop. These fundamental strings, as Dr. Heckman described, can exist as either closed strings, open strings, or even strings that have more than two ends, “like phases of water.”1 Physicists look to determine how these strings interact to create the world around us. Current research in string theory attempts to use its models to solve the problems modern physics can already answer. By proving its legitimacy, string theory will be able to solve more advanced problems that modern physics cannot.

Mathematics is important to string theorists because sometimes this nearly too-simple way of thinking is difficult to envision, but can make sense mathematically. Mathematicians, like physicists, find this field of research extremely interesting because “it points the way to new mathematical structures,” because “it doesn’t respect the usual rules of the game.”1 Geometry cannot be rigidly defined, but defined to fluctuate and change. The theory of gravity on large scales concerns itself with easy-to-use fixed geometries but, according to quantum mechanics at the subatomic level, matter is always contorting. String theorists relate gravity and quantum mechanics to make these two ideas one-in-the-same and form a theory of quantum gravity.2 Dr. Heckman’s research hinges on working with postdoctoral students and graduate students. When Dr. Heckman comes up with a new idea, he bounces it off many other researchers at conferences to formulate a plan for solving the problem posed. His group combines researchers in the disciplines of physics, mathematics, and computer science. It’s more of a “collaborative effort than a lone theorist [shut in his office for days at a time] studying this.”1 One project that Dr. Heckman has been involved with is trying to understand a class of phase transitions that exist in six dimensions. He at-

physical science

tempts to classify the types of transitions that happen in upper dimensions, like the melting or freezing of water in our three dimensional space. “What happens if we take these six dimensions and bring it into five dimensions, four, three, two, or one” is something that Dr. Heckman and his collaborators

“To think about the world differently, the first string theorists replaced the notion of particles as point-like structures with something that was more spread out in the shape of a onedimensional loop.” ask themselves.1 This project would provide a schematic for how things work that are currently unimaginable, like motion between dimensions. Grasping the movements of Mister Mxyzptlk, a six-dimensional being in Superman, may not be so far off.

The potential of this research is incredible. “If we had absolute predictive power, we could start to understand what happens to nature as we go up in energy scales,” which means we could begin to understand things like black holes.1 There are a lot of things about black holes, and the universe in general, which we have yet to fathom. There are so many questions that are still unanswered. How did the Big Bang happen? Is there only one universe? String theory could serve as a bridge to not only other dimensions, but to a more comprehensive understanding of the principles that govern the physical world.

References

1. Interview with Jonathan Heckman, Ph.D. 02/14/17.

2. Kaku, M. (1993). Oxford University Press. Manuscript submitted for publication, City College of the City University of New York, New York.

Figure 2. Artistic depiction of the multiverse. Image courtesy of Spiritual Unite.

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physical science

A PROBE INTO THE BEGINNING OF TIME I N V E S T I G AT I N G T H E F I R S T S ECO N D O F THE UNIVERSE B Y PA T R I C K G O R M A N

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Illustration by Isys Hennigar

he first second of the universe. This is one of the principle concerns of Dr. Adrienne Erickcek, an Astronomy Professor in the UNC-Chapel Hill Physics and Astronomy Department. Following the Big Bang, a series of events took place that set up the universe for the next few billion years. After a stage of completely incomprehensible quantum gravity, inflation occurred almost instantaneously, around the 10-30 second mark. The universe grew spontaneously from something smaller than the size of a proton to something the size of a grapefruit due to an immense amount of pressure and energy. Then comes the area of Dr. Erickcek’s research, the missing second between the end of inflation and the beginning of a heat and radiation dominated universe.

The “hot fireball universe” produces electrons, protons, and neutrons as the universe cools, which then form into light elements by nuclear fusion: hydrogen isotopes, helium, and lithium.1 But what happened in the one second following inflation and before matter began to condense into particles?

The missing second is the link between the end of inflation, where only the ‘inflaton’ exists (the particle that drove inflation), and the radiation-dominated universe. If we can look back in time at these quantities, then we can clarify what happened in the missing second. This is the key to Dr. Erickcek’s research. “Can we get an observational probe into this first second? The answer is maybe,” she said.1 Of the different ways to determine the conditions of the universe during the missing second, Dr. Erickcek and her team focus on dark matter formation and interactions to analyze that missing second. Despite there being six times the amount of dark matter in the universe as there is normal matter, there has yet to be a detected dark matter collision. Dark matter is among the most elusive mysteries of modern cosmology, with only theories standing in for the qualities of how it acts, in part

because it is so hard to detect. A particle of dark matter is theorized to be electrically neutral at high temperatures, massive in relation to a proton or neutron, stable, and its own antiparticle. Despite it being its own antiparticle, collisions are rare and generally difficult to detect, since there is no electrical attraction or repulsion between dark matter particles, and therefore no major force Dr. Adrienne Erickcek to draw two particles together on a collision course. However, collisions of dark matter would give off gamma rays, which is something Dr. Erickcek and other researchers can investigate.

Of the proposed structures of the universe during the missing second, Dr. Erickcek focuses on two possibilities: a radiation-dominated second, thus simply leading to the following phase, or a matter-dominated universe, which she finds more promising.2 Each of these depend on what happened to the inflaton after inflation; it either decayed into energy and radiation or remained as matter. In the case of a radiation-dominated phase, gravity would have little effect on the material of the universe as it expanded through the missing second, while pressure, due to the high temperature and energy of the universe, distributed all the matter throughout the universe rather than clumping it together. In a matterdominated universe, fluctuations in density, from the inflation

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Carolina Scientific period, would allow gravity to build structures together that create clumps of matter distributed throughout the universe.

Having clumps of dark matter greatly increases the likelihood that dark matter will collide and release gamma rays, which can be detected more often in a matter-dominated universe.2 In the standard model, clumps of matter are rare; all of the matter in the universe is spread out and collisions of dark matter are rare. This suggests that the state of the universe, be it primarily radiation or matter, can be determined based on composition of the universe in the first second. Density perturbations, relating to how the density of matter is distributed in the universe, relates to the annihilation and collision rate of dark matter in the early universe.3 Dr. Erickcek seeks to measure the difference in annihilation between a radiationdominated universe and a matter-dominated universe, focusing primarily on the latter.

Should it be proven plausible, this research could open the field of early universe formation by offering a new possibility beyond the standard model. If a matter-dominated universe is proven to be true, other dark matter candidates become more plausible.3 This broadens the possibilities for the events of the early universe while offering new theories related to dark matter. In offering support for a matter-dominated universe, the theories supporting dark matter are also supported, since the annihilation detection would offer evidence for dark matter properties and interactions. This would suggest some idea of how the inflaton could be defined, leading to a better defined image of inflation and its effect on the missing second. Ultimately, this is another stepping stone in

physical science

BUT WHAT HAPPENED IN THE ONE SECOND FOLLOWING INFLATION AND BEFORE MATTER BEGAN TO CONDENSE INTO PARTICLES?

the way of discovering the fundamental development of our universe, reaching closer and closer to the spark that began it all.

References

1. Interview with Adrienne Erickcek, Ph.D. 02/14/2017.

2. Erickcek, A.L. APS Phys. 2016, 94.

3. Erickcek, A.L. APS Phys. 2015, 92.

Figure 1. (Left) A density projections of an early era without matter domination at a scale of 0.025 parsecs. (Right) A density projection of an early era with matter domination, forming far more substructures where dark matter collisions could occur. The scale is 0.025 parsecs. Images courtesy of Dr. Adrienne Erickcek.

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physical science

Shedding LITE: Optimization of the Light Sheet Microscope

By Richard Chen

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hen Tanner Fadero, a first-year Ph.D, student, entered the Maddox Lab, he would never have guessed that he would be inventing a novel microscopy technique. Fadero joined the lab as a cell biologist, intent on studying the dynamics of the cytoskeleton through model organisms. When asked by his principal investigator, Paul Maddox, about light sheet microscopy, Fadero responded with “never heard of it.”1 Dr. Maddox asked Fadero to construct a light sheet microscope (not to be confused with a light microscope) using blueprints that Dr. Maddox found on Google. Together, they began building the microscope from parts found around the lab. They found that there was a fundamental tradeoff to the light sheet microscope.

Modern light microscopes utilize fluorescent proteins that were artificially inserted into the organism to image the desired part of a cell—whether it is the chromosomes as they condense before cell division or the ribosomes as they make proteins. Light microscopes produce images by shining light in a straight line directly through the entire sample towards the objective lens, which captures and resolves the light emitted from excited fluorescent proteins into the eyepiece. However, there are several problems with light microscopy.

Photobleaching occurs when light breaks apart a fluorescent molecule in a sample, thereby reducing the fluorescence of the molecule.2 Phototoxicity results when fluorescent molecules excited by the light microscope interact with oxygen to produce free radicals that can damage the subcellular components, which could potentially disrupt the experiment.3 The signal to noise ratio is used to characterize the effectiveness of a microscope in capturing the fluorescence of the fluorescent molecule. Light sheet microscopes were invented to reduce the impact of phototoxicity and photobleaching on experimental data and improve the signal to noise ratio in comparison to light microscopes with fluorescent proteins.

Light sheet microscopes selectively shine relatively low amounts of light on the area of the sample at a 90-degree angle relative to the objective lens (Figure 2). This distinct method of exciting the fluorescent proteins has one major disadvantage.

Light sheet microscopes produce shadows in the image and sacrifice resolution because light sheet microscopes shine light at a 90-degree angle and must station the objective lens

further away from the sample. Higher resolution objectives can take clearer images but must be stationed closer to the sample and, sometimes, even immersed in the sample. With light sheet microscopes, the objective must be stationed far-

Tanner Fadero, Ph.D. candidate, and Dr. Paul Maddox

Figure 1. The final LITE sheet prototype. Courtesy of Dr. Maddox.

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Carolina Scientific ther away from the sample, forcing light sheet microscopes to utilize lower resolution objective lenses. Fadero and Dr. Maddox were not satisfied with the institutionalized model of light sheet microscopes using low resolution objectives.

The process of improving the light sheet microscope involved breaking the preconceptions of what the ideal light sheet microscope is. In the field of microscopy, a light sheet microscope is defined by the 90-degree angle formed by the light source and the objective lens. Fadero and Dr. Maddox found through calculation that adjusting the angle at which the light excites the sample will allow for the objective lens to be stationed closer to the sample, making higher resolution objectives compatible with the light sheet microscope. After months of toying with prototypes, Fadero and Dr. Maddox developed the LITE (Lateral Interference Tilted Excitation) sheet microscope which shines light at an 88-degree angle rather than the ideal 90-degree angle (Figure 1).1 The LITE sheet microscope can use an objective lens that captures 82% more light and achieves 36% higher resolution than its standard counterpart. This seemingly minor tilt greatly improves resolution with minor sacrifices in the ability to selectively illuminate areas of the cell. Dr. Maddox, a microscopy veteran with over fifty published papers in cell biology discoveries and microscopy techniques, recognized the value of their development and decided that they should patent it. Dr. Maddox and Fadero successfully patented the LITE sheet microscope with the help of the UNC Office of Commercialization and Economic Development (OCED), a department that facilitates in the patenting process and assists UNC-based startup companies.

Because the LITE sheet microscope was developed in a UNC lab with funding from UNC, the university owns a majority of the patent with Fadero and Dr. Maddox owning less. While this may bother some, it did not bother Fadero.

At the end of the day, Fadero is a cell biologist determined to disseminate the dynamics of the cytoskeleton.

Fadero believes that people he met and the experience he gained from making a light sheet microscope are worth far more than the money he would have made from trying to patent the LITE sheet microscope without the help of UNC. Their invention has already garnered attention from several labs at

physical science

Illustration by Larissa Wood UNC for its optimal image quality and advantages in preserving the integrity of their experiments through reductions in phototoxicity and photobleaching. Fadero highlights that this contribution will enable deeper and more powerful inquiries into the logistics of the cell.

References

1.Interview with Tanner Fadero. 02/17/17.

2.Nikon. Fluorophore Photobleaching. Retrieved from www. microscopyu.com/references/fluorophore-photobleaching.

3.Nikon. Phototoxicity in Microscopy. Retrieved from www. microscopyu.com/references/fluorophore-photobleaching.

Figure 2. Standard Light Sheet Microscopy Diagram.

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physical science

Figure 1. Black phosphorous molecules are bonded to make a buckled appearance. Photo by Kaci Kuntz.

WHAT’S ON THE SURFACE? Investigating the Oxidation of 2-D Black Phosphorus

By Mackenzie Price

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magine what it would it be like to be a part of scientific history. Here at the University of North Carolina, the Warren Lab is doing just that as they strive to impact the scientific community through their study of two-dimensional materials. “Improving our understanding of the world is the reason I study chemistry,” says Ph.D. student Kaci Kuntz.1 Kuntz has been a member of the lab for 2.5 years studying the sustainability, optics, and electronics of 2-D materials.2 2-D materials are a novel discovery that have opened a world of possibilities as their properties are still being discovered. The applications for these tiny specimens range from devices that can store energy to ultra small electronics.

Kuntz’s current research has her working with black phosphorous as a 2-D nanomaterial, which is so small that it is invisible to the naked eye. This black, flakey crystal has posed one major problem for the lab. It oxidizes when exposed to air and water.2 Oxidation is the same process that causes fruit to brown and rusting to occur. This makes it impossible to use in future applications, because the material is breaking down whenever it meets air. Kuntz hopes to explain how and why the oxidation of 2-D black phosphorous is occurring.2 Understanding the properties of a single layer of black phosphorous will help define its future applications.

The process of making the large crystalline structures of black phosphorous into flakes that are a few nanometers thick is a long one.2 To put it in perspective, if you stacked 200,000 of these 2-D flakes together, they are roughly the same size as the diameter of a single strand of hair, or the thickness of

a piece of paper.1 This process is known as liquid exfoliation, and the Warren Lab is one of the first to use it.2 This method of exfoliation has proven the most efficient. It allows Kuntz to collect large amounts of monolayer material at once compared to the previous technique, which only gives a single monolayer. 2 The uncommon 2-D material of black phosphorous has unique electronic and optical properties that Kaci Kuntz, Ph.D. Candidate change as it is made thinner. These molecules are made up of two stacked phosphorous atoms that make a “buckled structure” (Figure 1).2 Once thinned, the layers can be reassembled to show the optical properties. Kuntz describes, “if you stack them together you are able to absorb different wavelengths of light over the visible spectrum.”2 This transfer of energy among wavelengths shows the materials potentials for use in devices that detect light. This is just one of the many applications of black phosphorous.

Currently, the greatest obstacle prohibiting the applications of 2-D black phosphorous is its sensitivity to air.2 Kuntz began her investigation by exposing the material to three

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Carolina Scientific

physical science

different environments, and studying the oxidation process in each. The material was placed in pure oxygen, pure water, and regular air, each for 18 hours. “So far we know that oxygen causes oxidation, water causes oxidation, and that water and oxygen cause very fast oxidation. We know that it’s going through [oxidation] stages, [which] eventually is where molecules are breaking off. So our material is disappearing with time.” 2 The next step was to view this process as it occurred.

Kuntz used transmission electron microscopy (TEM) to transmit electrons through the flakes, allowing them to visualize the surface of the material. What Kuntz found was more than interesting. She saw that that oxygen oxidizes the entire surface of black phosphorous at the same time, but when exposed to water, only the locations most likely to host deformities were pitting. These sites included edges, grain boundaries (where imperfect bonding has occurred), and edge states of thicker layers (figure 2).2 Kuntz explains the magnitude of their discoveries, “you would think that the thinner flake is going to oxidize faster than a thicker flake, but oxidation is occurring at thicker flakes which is really weird, and goes against what everyone knows about 2-D materials.” 2 That was not the only confounding discovery Kuntz and her team have made. They discovered that when the layers of black phosphorus were exposed to pure oxygen, a layer of phosphorus oxide was being created in place of the original layer of phosphorous. Kuntz’s excitement was tangible as she described the phenomena, “This 2-D oxide has never been made [freestanding] before, and its electron properties completely change, meaning that it has a different set of applications than the black phosphorous we are studying.” 2 Kuntz has recently published a paper on the labs findings. She hopes that her work will inspire other chemists to delve further into the world of 2-D black phosphorus. Another such project entails exposing the material to oxygen or water for short periods of time and stopping the oxidizing process early. In doing so, chemists would be able to manipulate the surface and find ways to halt oxidation creating a functional material. This material could be used as efficient solar cells and transistors in computers, to name a few of the many modern day applications.2 For Kuntz, the world of two-dimensional materials offers an endless array of things yet to be discovered. “I am most excited when I do research, because I have the opportunity to see things few or no other people have ever seen!”1 Looking towards the future Kuntz hopes to continue doing groundbreaking research. However, her true passion lies in teaching.

One day, she could be joining the ranks of inspiring professors here at UNC helping to shape the future chemists and innovators of the world.

References

1. Interview with Kaci Kuntz, Ph.D. Candidate. 02/01/2017.

2. Email correspondence with Kaci Kuntz, Ph.D. Candidate.

02/2017.

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Figure 2. (Top) The surface of 2-D black phosphorus monolayer after being exposed to pure oxygen. Photo

by Kaci Kuntz. (Bottom) The pitted thick edges of 2-D black phosphorus monolayer after being exposed to water. Photo by Kaci Kuntz.

life sciences

Intelligent by Degrees

By Holly Bullis

Illustration by Alexandra Corbett

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he brain is a complex organ, made of many different parts that function in interconnected ways. Several approaches can be used to study the brain, such as behavioral observation, which looks at how the brain works through problems and which cues an animal uses to learn. Other approaches include studying molecular structure- the specific chemical compounds and protein structures used in a neural process-and historical behavior, which examines how the intellectual processing of the studied species has changed over time.

To tackle these levels of observation, Dr. Sabrina Burmeister studies frogs. It was a little rational and a little coincidental that she ended up working with frogs, Dr. Burmeister commented after referencing a brief foray with fish research.1 Frogs are easy to study because, like mice or lab rats they are small and easy to take care of. But unlike mice, frogs are less prevalent in labs, so their genes are not mapped and they do not have a history of study like lab rats do. Dr. Burmeister, a professor in UNC-Chapel Hill’s biology department, heads a neuroscience lab of graduate students interested in the neural makeup of frogs.2 Dr. Burmeister is specifically interested in the hippocampus, a region of the brain integral in the pro-

"Dr. Burmeister and her team combine aspects of behavioral observation, brain chemistry, and natural history to paint a comprehensive picture of the hippocampal processes."

cessing of memories.3 While frogs do not have a hippocampus exactly like a human’s, they have a region of the brain that functions the same way as a human hippocampus.1 The Burmeister lab is currently involved with a few different studies, and one of those ongoing investigates the hippocampus of two frog species: túngara frogs and dart frogs. Though similar, Dr. Sabrina S. Burmeister both species behave differently and so do their brains. Dr. Burmeister and her team combine aspects of behavioral observation, brain chemistry, and natural history to paint a comprehensive picture of the hippocampal processes.

The Burmeister lab uses a series of behavioral experiments to investigate the behavioral flexibility of both frog species. Specifically, they want to know if the frogs can learn and unlearn things they are taught.1 This is called neural plasticity, the ability to scrap something that was previously learned and create a new association. To test this ability, the frogs are given a choice between two doors with different colors painted on them. In the first phase of the experiment, Door One had a reward behind it. After a few trials, both species of frog learned to associate Door One with the reward and chose Door One over Door Two. In the second phase, researchers reversed the task,

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Figure 1: Túngara frog. Courtesy of Brent Gratwicke. placing the reward behind the opposite door. The researchers were investigating whether the frogs would unlearn the association between Door One and the reward and re-learn an association between Door Two and the reward. One species of frog could not accomplish the task. Despite multiple trials wherein the reward was behind the opposite door, one species of frog consistently went to Door One, unable to unlearn the association. The second species was able to unlearn the association and learn a new association between Door Two and the reward. This species of frog could learn, unlearn, and relearn quicker each time the reward was switched to a different location, but for the first species it was impossible. This means there is something different about the way the two species learn. One species does not have the neural wiring to unlearn associations once learned, while the other species can- an ability strengthened through multiple trials. To understand why these two species have different abilities when it comes to learning and unlearning, the Burmeister lab investigates a specific behavior of the species: selecting breeding pools. During breeding season, one species goes back to the same pool each year while the other species breeds at different pools in the same area. These two species may have been pushed by their environment to adapt certain habits when it comes to selecting their breeding pools, and this may have influenced their neural wiring when it comes to learning and unlearning things. To investigate further, the Burmeister lab looks at what cues the frogs are paying attention to when they are learning something.

In the next behavioral experiment, researchers placed one frog in a maze. Over multiple trials, the frog became acquainted with the maze, and once they were able to navigate the maze reasonably quickly, the researchers changed environmental cues within the maze, sometimes changing the colors in certain sections of the maze and other times changing the colors of the endpoints of the maze. In observing the frogs’ reactions to these cue changes, the researchers found that one species of frog associated its memories of the maze with cues around the doors and the other species associated memories with the color cues on the doors. For one species, changing the color of the endpoints of the maze had no effect on the frog’s ability to navigate, while changing the cues leading up to the door affected the frog’s navigation, while the

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other species was tripped-up by the change of a different cue.

This showed that each species creates different associations in order to learn the maze. This means that the frogs are attuned to different things, lending further evidence to the idea that the mechanisms and process of accomplishing tasks are different for the two species.

To understand more about what proteins and chemicals are used to create the frogs’ memories, the Burmeister lab also dissects frogs’ brains- specifically the hippocampal region- to see what molecules are active in a particular memory process. They pinpoint the active molecules by collecting and coding the RNA strands present in the cells at that time to discover what proteins the frog’s brain is producing in order to accomplish the memory task. What Dr. Burmeister found was that there is a degree of separation between the neural mechanisms of the two frog species. Their mental behavioral functioning, the proteins in their hippocampus during this

“Neural plasticity: the ability to srap something that was previously learned and create a new association.” processing, and their behaviors are different. For this type of study, it is common for things not to match up. As it turns out, many other such studies have been conducted looking at the behavior and chemistry of two related species but, despite the mismatching species, the degrees to which they mismatch are similar. This may point to a similarity between the niches different species occupy in relation to each other- an overarching evolutionary trend in neurological data.1

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Figure 2: Frog. Courtesy of Creative Commons.

References

1.Interview with Sabrina S. Burmeister, Ph.D. 02/01/2017.

2.Burmeister, S. S.; Yuxiang, L. “BurmeisterLab@UNC.” Burmeisterlab.org. The University of North Carolina, Web. (Accessed 02/27/2017).

3.Striedter, G. F. “Hippocampal Lesions Impair Allocentric Navigation.” Neurobiology: A Functional Approach. New York: Oxford UP, 2012. 365-66. Print.

life sciences

Out of the Loop

By Haley Clapper

Dr. Jill Dowen f all the genetic information in one of your cells could be stretched out to form a single string, it would be about two meters long. How can the information that codes for all life exist within a nucleus that is only about six micrometers (0.000006 meters) in diameter? The human genome is tightly folded and packaged into the three-dimensional nucleus, creating a dense, entangled mass of all the information that makes you who you are (in a physical sense, of course). To fit into a compact mass, DNA strands must condense to form loops.

If this organization of the genome is altered in the slightest way, an organism can experience severe consequences, including developmental issues and disease.

Dr. Jill Dowen, Professor of Biochemistry and Biophysics at UNC-Chapel Hill, studies how alterations in the genome affect human health. Her research specifically focuses on how the

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genome is organized within the nucleus and how the phenomenon of DNA looping acts dynamically to express changes in the genome. She explained how her research is “at the interface of basic biology and human health.”1 She seeks to uncover the relationship between epigenetics and disease, a discovery that could transform the treatment of illnesses.

In all living organisms, DNA (deoxyribonucleic acid) serves as a template with which to transcribe RNA (ribonucleic acid), which is translated into amino acids, the building blocks of proteins that are essential to life. These proteins make up all cell structures and perform different functions. Genes are specific sections of DNA that contain unique codes for various proteins with different functions. For example, a muscle cell and a skin cell from the same organism each perform different functions, but they each contain the same DNA. While DNA mutations can lead to dysfunctional proteins, changes in gene expression do not always occur directly within the DNA sequence. Instead, gene expression can be altered by epigenetic factors from the environment, such as the misbehavior of transcriptional factors and regulatory proteins. Regulatory proteins can induce or repress the ability of RNA polymerase to synthesize RNA copies from the DNA template, a process called transcription. Regulatory proteins bind to pieces of DNA, like en-

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Illustration by Stephanie Dong hancers and promoters, and regulate the proper activity of a gene.2 DNA looping occurs when regulatory proteins interact to shape DNA strands into loops.

Dr. Dowen observes these protein interactions and how disrupting them can alter gene expression. Particularly, she studies the CTCF protein, which acts a boundary of the DNA loop and blocks interactions between enhancers and promoters.3 CTCF plays the vital role of binding DNA strands together to complete loops. If the protein’s function is interrupted, the loop can dismantle and change gene expression.

To further understand how regulatory proteins like CTCF affect gene expression, Dr. Dowen uses the CRISPRCas9 system, a revolutionary method of editing genes by activating, repressing, or deleting genes. With CRISPR-Cas9, a boundary region of a DNA loop can be deleted, opening the loop and changing the direction of transcription. “In normal cells, a loop is formed, and an enhancer

Figure 1. A Dowen lab member prepares her samples for a DNA digest.

Carolina Scientific drives the expression of a gene inside,” Dr. Dowen explained. “When we disrupt the loop, the enhancer can gain access to genes that were originally outside of the loop and were expressed at lower levels or not at all before the loop opened.”1 Consequently, newly expressed genes could alter cellular function with consequences detrimental to the organism’s health. If genes are expressed abnormally in a cell, the cell could lose its identity and differentiate into another cell type; loss of identity is a critical factor in disease development.

Cancer cells, for example, grow and replicate uncontrollably as result of increased expression of gene mutations. If a certain gene mutation that is not normally expressed is activated after the disruption of a DNA loop, the organism could develop cancerous cells.1 The Dowen Lab’s initial studies focused on genes of embryonic stem cells in their pluripotent state—the state in which stem cells have potential to develop into any type of cell. In addition, the Dowen Lab observes the behavior of leukemia cell lines. “We want to understand how changes in DNA loops might contribute to the tumorigenesis

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process in leukemia,” Dr. Dowen stated.1 She believes that new treatments could emerge from understanding the relationship between gene expression and human disease. Dr. Dowen predicts that, in the future, small molecules may be used to repair DNA loop breakages or entirely prevent them from breaking. It is possible that entire “libraries” of small molecule therapies can be tested through robotics to see which have the greatest impact on repairing or preventing loop breakages.1 With knowledge of DNA looping, treatment of diseases like cancer could change drastically.

Dr. Dowen hopes that her research will benefit future medical practices and will keep people “in the loop” about human development and disease.

References

1. Interview with Jill M. Dowen, Ph.D. 02/08/2017.

2. Phillips, T.; Hoopes, L. Nature Education. 2008, 1, 119.

3. Holwerda, S.; de Laat, W. Philos.

Trans. R. Soc. London Ser. B. 2013, 368, 1620.

Illustration by Alexandra Corbett

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College of Osteopathic Medicine • School of Pharmacy • School of Dental Medicine School of Graduate Studies • Masters/Post Baccalaureate LECOM Main Campus, 1858 West Grandview, Blvd., Erie, PA 16509

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Viral Survival: Understanding How Viruses Evolve Host Shifts

By Kristi Dixon Illustration by Isys Hennigar

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volution, in the words of Charles Darwin, is “descent with modification.” Although it is rare, sometimes when genes are passed on from parent to offspring, there are changes in the genetic sequence. These changes are known as mutations and are significant in understanding evolution.

An important reason scientists need to study evolution and how it changes genes over time is to learn all they can about diseases such as HIV, influenza, and Dengue fever that can evolve quite rapidly. In the natural world, a mutation that causes any form of disadvantage means life or death. However, not all mutations are harmful; minor mutations can be beneficial to an organism.

At UNC-Chapel Hill, Dr. Christina Burch takes an experimental approach to studying evolution. She works primarily with bacteriophage, or viruses that infect bacteria, which have an RNA genome. These phages have the interesting property of an unusually high mutation rate. The viruses evolve so quickly in the lab that the mutations can be visibly seen in as little as a week. “One of the reasons I took this job is that the medical school- the microbiology department- has a lot of virologists that study RNA viruses [and they] understand better than anyone that we need to figure out how viruses evolve,” Burch said.1 She explained that a common theme that occurs between her lab and her collaborative work with the human virus labs has to do with host shifts- a virus’s ability to change what organisms it can infect.

The phage under scrutiny in Dr. Burch’s lab is referred to as φ6 (phi-six). The phage φ6 infects the bacterial crop pathogen Pseudomonas syringae. In her experiment, Dr. Burch has access to different strains (genetic variants) of P. syringae.

The standard lab strain of φ6 naturally infects some of these strains (referred to as standard hosts), while it is not able to infect others (referred to as novel hosts).1 The standard hosts

are probably what φ6 infects in the wild, making it a preferred host over any novel strains. The purpose of the experiment is to determine whether φ6 is likely to evolve the ability to infect alternate hosts.

This is tested by subjecting φ6 to various ecological challenges.

The results of this experiment are measured in the appearance and freDr. Christina Burch quency of generalists- φ6 that have the ability to infect both standard and novel hosts.1 Once a phage acquires a mutation that enables it to infect the novel hosts, it will pass that ability to its descendants. This clearly demonstrates “descent with modification.”

One ecological factor manipulated is the amount of standard hosts available to φ6.2 When the standard hosts are abundant, no pressure is exerted on the viruses because their preferred host is in abundant supply. While the mutation that expands host range can still occur randomly, it does not overcome the population because there is no need; there are enough standard hosts to sustain φ6.

Another ecological factor manipulated in Dr. Burch’s experiments is the abundance of novel hosts. When novel hosts are common, a mutation that expands host range is beneficial.

This is because the system will be under stress when the preferred standard host is depleted and the novel host remains untouched. In this case, if φ6 cannot infect the novel host,

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Figure 1. Frequency of generalist viruses vs. test tube transfers. Courtesy of Dr. Burch then it cannot infect any host- rendering it unable to pass on its genes. Therefore, if a mutation that expands host range occurs, it is highly likely to overcome the population (represented in warm colors, Figure 1).2 These mutations are completely random, but the sheer magnitude of viruses replicating increases the chances that the “right” mutation will appear and allow a host shift.

In the case that novel hosts and standard hosts are both in short supply, it is not as beneficial to gain the ability to infect novel hosts. This means that both randomly mutated φ6 and non-mutated φ6 are passing on their ability to infect hosts and they are coexisting (represented with cool colors, Figure 1).2 The frequency of generalists fluctuates because survival is not dependent upon which host is available.

These experiments show that with the right mutation, a virus can come back from the brink. Dr. Burch’s experiments are only one example of a virus evolving a host shift. In 2015, Kayla Peck, one of Dr. Burch’s graduate students, compiled a report on coronaviruses- “a diverse family of viruses that infect

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a wide range of avian and mammalian hosts.”3 While this family of viruses is associated with these animals, there are human coronaviruses that likely gained the ability to infect humans through host shifts. This is an unfortunate occurrence for humans, as some of the viruses can cause serious disease and death. Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, both caused by coronaviruses, have been the cause of over one thousand deaths.3 People are likely more familiar with this concept as it relates to influenza; the public has to get a new vaccination for influenza every year. This is because the flu virus develops traits to get around the updated immune system from previous vaccinations and exposures. Other examples include swine flu and bird flu that ruffled a few feathers in the recent past in developing host shifts. Dr. Burch clarified, “flu genes move from bird flu into human flu. Although we don’t test movement into humans in the lab, we use the phage and all the hosts as a tool kit for asking the same kinds of questions: Let’s understand what mutations can enable a virus to infect a host it’s not initially able to infect.”1 The flu virus must mutate or be foiled via vaccine, just as the struggling phage must mutate to infect an alternate host, lest it infect no host at all.

References

1. Interview with Christina Burch, Ph.D. 02/10/17.

2. Bono, L. M.; Gensel, C. L.; Pfennig, D. W.; Burch, C. L. Proceeding of the Royal Society B: Biol. Sciences. 2015. 10.

3. Peck, K. M.; Burch, C. L.; Heise, M. T.; Baric, R. S. Annual Review of Virology. 2015. 9, 95-117.

“These mutations are completely random, but the sheer magnitude of viruses replicating increases the chance that the “right” mutation will appear and allow a host shift.”

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CORAL REEFS IN DECLINE: WHAT WILL IT TAKE TO SAVE THEM

illustration by Stephanie Dong

RESTORING REEFS WILL TAKE A GLOBAL EFFORT

BY SARA EDWARDS

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Imagine you are walking through a forest. Sunlight filters through the surrounding trees and the sounds of singing birds and small animals rustling through dead leaves fill the air. Even though the trees are smaller and fewer in number than they were thousands of years ago, and there are no more wooly mammoths or dire wolves roaming around, the forest is still beautiful.

Dr. John Bruno Dr. John Bruno, a professor and researcher in the Biology Department at UNC-Chapel Hill, described the current state of coral reefs in a similar way. Like the trees that make up a forest, corals are the building blocks of reefs, but they are dying off rapidly. According to Dr. Bruno, “It’s hard to know why corals are dying because there’re so many potential causes… It’s like a murder mystery with too many suspects.”1 These “suspects” range from local causes like nutrient pollution to global causes like climate change. Scientists are still determining the relationship between these seemingly disparate causes in order to formulate the most informed approach to environmental restoration (Figure 1).1,2 Because coral reefs are the habitat for a variety of marine organisms, their degradation leads to a decline in the abundance, diversity, and biomass of fish species. This in turn affects the human communities that depend on the reefs for tourism revenue, food, and protection from storms. “There’s big implications for people, coastal communities, cultures, and economies; it’s not just about the fishes and invertebrates that inhabit the reef,” said Dr. Bruno.1 Caribbean nations are especially vulnerable because the destruction of reefs, combined with rising sea levels and intensified storms, is a recipe for disaster.

One of the ways Caribbean nations are trying to com-

Figure 1. Diseased coral in a reef near Akumal, Mexico. Coral diseases have increased significantly in the past decade, likely because of human pollution. Photo courtesy of Dr. John Bruno.

Figure 2. A diver studies bleached coral in Virgin Islands National Park Photo courtesy of National Park Service via Wikimedia Commons.

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threatened by poaching. Many Belizeans turn to illegal fishing to support themselves and their families. In some places in the Caribbean and Africa, weaponized enforcement is necessary for governments to protect reefs (Figure 3), but the Belizean government has limited resources to enforce restrictions. The situation in Belize is common across the developing world, where MPAs are sometimes called “paper parks” because they look good on paper but do not actually achieve many conservation goals.1 Other than managerial issues, the largest contributor to the global coral decline is probably climate change. Over the past 30 years, about two-thirds of living corals worldwide have been lost due to ocean warming, which contributes to coral bleaching and disease (Figure 4).1 The Great Barrier Reef, the world’s largest and most iconic reef, is experiencing massive bleaching despite protective measures because the regional management efforts cannot do much to relieve global pressures on coral. “We really have to tackle carbon emissions in order to have hope in restoring coral reefs to the way they were when I was a kid,” Dr. Bruno said. “I won’t live to see that.”1 Saving coral reefs is not impossible. Although most reefs in the Caribbean are severely damaged, Dr. Bruno said there are still “bright spots” like the reefs of Bermuda and Curaçao that give him hope.1 These places will probably hold out for a few more decades if conditions remain the same, but in order to preserve coral reefs in the long run, changes need to be made. On a local scale, MPA managers could do a better job of enforcing fishing restrictions if they had more resources.1 Additionally, MPAs themselves need to be larger and more strategically placed to encompass critical areas like spawning grounds. Investments from NGOs and other aid organizations would help impoverished nations implement these changes.

Dr. Bruno is still optimistic about the future. “There’s no extinct coral species, they’re all still there. If we tackle these problems, I’m sure they will recover.”1

Figure 3. The Belizean Army (here training with the US Navy) sometimes patrols MPAs to discourage poaching.

Photo courtesy of: Colin-47, CC-BY-nd-nc-3.0.

Figure 4.This graph shows an increase in the heat content of the oceans from 1955-2010. Rising ocean temperatures are a major factor in the global decline of coral reefs. Image courtesy of NOAA via Wikimedia Commons.

References

bat declining coral and fish populations is maintaining protected marine areas, or MPAs (Figure 2). These zones have different levels of restrictions, including those where all fishing is prohibited (called “no take zones”) and those that allow some fishing (called “general use zones”).2 The purpose of these regulations is to conserve the ocean’s biodiversity and habitats.

Dr. Bruno and other marine scientists have studied a network of MPAs off the coast of Belize in order to assess their effectiveness at improving indicators like coral cover and fish biomass in ecosystems. Compared to reef surveys conducted in the 1990s, a 2009 survey of both protected and unprotected areas showed that MPAs had no effect on fish biomass, coral cover, or coral recruitment.1,3 To quote Dr. Bruno: “In a sense, this management strategy is having no effect on any measurable parameter that gives you an indication of the state of the ecosystem.”

For Belize, MPAs just aren’t working. Dr. Bruno believes that part of the problem is that the reserves are small, so fish can easily travel outside protected boundaries and fall victim to fishing. Even when fish are within an MPA, they are often

1.Interview with John Bruno, Ph.D. 02/14/17.

2. Cox, C.; Valdivia, A.; Mcfield, M.; Castillo, K.; Bruno, J. Marine Ecology Progress Series. 2017, 563, 65–79.

3. Bruno, J. F.; Valdivia, A. Scientific Reports. 2016, 6, 29778.

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Scaling Down to Ramp Up

BY SAMUEL GOLDSTEIN

Figure 1. Example of a biomedical microchip.

This specific microTAS was designed to simulate the respiratory system. Photo by WYSS INSTITUTE/DESIGN MUSEUM

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he all-time bestselling pharmaceutical drug in the United States was almost never commercialized. From its inception in 1996, Lipitor (a drug that decreases levels of harmful cholesterol) took roughly twelve years and over one billion dollars to bring into the market.1 In 2014, a study conducted by the Tufts Center for the Study of Drug Development estimated the cost of gaining market approval for a new drug at $2.6 billion!2 The largest contributing factors to these astronomical costs, which prolong the drug development process and ultimately prevent people from receiving potentially lifesaving medicine, comes from the ethical issues that arise from human drug testing. Dr. Nancy Allbritton, Chair of the Joint Department of Biomedical Engineering between the

The Allbritton lab is working on creating microengineered systems that simulate human cellular environments with the goal of substituting current modes of drug testing...with a so-called organ-on-a-chip.

University of North Carolina at Chapel Hill and North Carolina State University, leads a specialized team of scientists dedicated to creating technologies that address this problem and other problems like it throughout the modern world.

The Allbritton lab is working on creating micro-engineered systems that simulate human celDr. Nancy Albritton lular environments with the goal of substituting current modes of drug testing, which are usually the cause of the aforementioned drug development problems, with a so called organ-on-a-chip. This solution is an example of a micro-total analysis system (microTAS), which replaces conventional cell culture methodology with liquidhandling circuit devices that reduce the scale of an experiment from an entire laboratory down to a single chip.3 The scientific properties that govern the movement of liquid on these chips is known as microfluidics. Because the technical aspects of these devices are so complex, the Allbritton lab is an amalgamation of experts from the fields of physics, chemistry, engineering, biology, and medicine.

As Dr. Allbritton put it, “I tell the biologists and the clinicians that our job is to make them famous…we solve their problems, but then they provide the specifications and application for our tools and technologies.”4 It is this symbiosis

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Carolina Scientific that drives the important revisions necessary to transform the lab’s prototypes into marketable products. For Dr. Allbritton, commercialization is paramount: “To me success is seeing my technology out there being used by others and they don’t even know I made it.”4 By virtue of working on some of medicine’s current challenges, Dr. Allbritton’s creations are able to fit seamlessly into the workflow of current research and make an impact.

For instance, the Allbritton lab has been able to optimize the regenerative efficiency of human colon epithelial stem cells on 3-D cultures.5 This research was conducted in order to expedite the drug development for inflammatory bowel diseases. The current methods of drug testing make it very challenging to assess the effectiveness of different colon medications in vivo (in living organisms). By finding proper incubation times, testing different materials and buffers, and determining the effect of varying concentrations of growth factors, the lab was able to create a microTAS that is virtually indistinguishable from the human gut. This device allows clinicians to view cellular activity in vitro (in a cell culture), which greatly enhances their ability to determine if certain medicines are effective.

Despite having already made headway in maintaining homeostasis (internal stability) for human intestine cells, Dr. Allbritton is very aware of the current limitations and the impending progress of this line of research. In to order accurately assess how the human body reacts to certain drugs, microchips will need to possess cells from more than one type of human organ. As explained by Dr. Allbritton, “The idea is that you will have all of the organ systems that will talk to each

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other. A lot of drugs you take in go in through your gut, they get absorbed in the small intestine, they are metabolized in the liver, they get secreted in the bile, they get reabsorbed in the colon or large intestines and they come back into the blood stream, and then they act on another organ.”⁴ In reality, researchers will need to include cells from all of these organs in order to track down all of a drug’s potential side effects. Although such a device is out of reach with current technology,

In the future, in a world full of specialized microTAS, the recurrent sluggish rate at which new drugs are put on the market will be a thing of the past. the limited feasibility and applicability of animal drug testing, which is being progressively phased out of Europe, makes the device’s development an international priority.6 In the future, in a world full of specialized microTAS, the recurrent sluggish rate at which new drugs are put on the market will be a thing of the past. Someday soon, it will even possible to create your own personalized medicine based off a microTAS generated from your very own cells.

References 1. Rowley, Laura. The Huffington Post. Pfizer’s Lipitor: The Blockbuster Drug That Almost Wasn’t.

2. Mullin, R. Tufts. Study Finds Big Rise in Cost of Drug Development. http://cen.acs.org/articles/92/web/2014/11/ Tufts-Study-Finds-Big-Rise.html (Accessed February 12, 2017).

3. Iwasaki, Y.; Seyama, M. NTT Technical Review. MicroTAS for Biosensors. 2015, 13(1).

4. Interview with Nancy Allbritton, Ph.D. 02/07/2017.

5. Asad, A.; Yuli, W.; Nancy, A. Journal of Biological Engineering. Optimization of 3-D organotypic primary colonic cultures for organ-on-chip applications. 2014.

6. Cruelty Free International. EU Ban on Cosmetics Testing. https://www.crueltyfreeinternational.org/what-we-do/ corporate-partnerships/eu-ban-cosmetics-testing (Accessed February 14, 2017).

Figure 2. Artistic depiction of a human-on-a-chip.

Courtesy of Adam Hayes.

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HIV BOUNCES BACK Figure 1. Scanning electromicrograph of HIV infecting T cells.

Photo courtesy of NIAID [CC-BY-2.0]

By Zarin Tabassum

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lthough researchers have made tremendous advancements in human immunodeficiency virus (HIV) treatment, the virus threatens to catch up with these modern efforts. Most patients on HIV medications have undetectable levels of the virus, but it still remains dormant within them. Drug resistance is a constant risk with pathogens, given their Dr. Ronald Swanstrom rapid growth and ability to evolve. While current drugs are effective in suppressing HIV today, there may come a time in the future when strains of HIV are drug resistant and the need for more effective drugs will arise. Dr. Ronald Swanstrom and his lab in the Biochemistry department at the UNC-Chapel Hill School of Medicine investigate the evolution of HIV in different cell types and how the virus ‘bounces back’ from dormancy after discontinuing therapy. New efforts are also underway to develop the next generation of drugs in order to reduce the chances of resistance and uncover HIV’s modes of action in different parts of the body.

Dr. Swanstrom focuses on various aspects of the HIV infection, especially the virus’ entry into different cells. Normally HIV infects T cells (Figure 1), which are white blood cells that help the body fight against infections, by taking over and using the cell’s machinery to multiply. As the virus spreads, the body is no longer able to protect itself from other diseases since T cells are central to immunity. Further, once the number of T cells decreases substantially, the virus can evolve to grow

in other cell types. Dr. Swanstrom’s lab investigates some variants of HIV that infect macrophages, which are another type of white blood cell that “eats” foreign substances. This type of infection, called a macrophage tropism (Figure 3), occurs in the brain and, as Dr. Swanstrom stated, “seems to be a compelling aspect of HIV pathogenesis because an ongoing infection in the brain affects your quality of life much more so than other localized infections.”1 The brain is special because it is separated from the rest of the body by the blood-brain barrier, which is highly selective for certain substances and has a decreased ability to recognize pathogens. Consequently, the virus is able to slip past the barrier and infect local cells, such as the macrophages that migrate into the brain.

Over the past several years, Dr. Swanstrom and his colleagues have investigated these macrophage-tropic viruses and found that they are able to enter macrophages more efficiently than when normal HIV enters T cells. Additionally, these variant viruses are more resistant to certain antibodies and more sensitive to others, suggesting some changes in viral entry.2 Despite these findings, the cause of the macrophage tropisms is still poorly understood. However, Dr. Swanstrom believes that “understanding the evolutionary pathway of these viruses may be significant in understanding how HIV infections are established in the brain and stay there even during therapy.”1 Additionally, Dr. Swanstrom and his team are studying the latent or dormant virus as it persists in the body. HIV cannot be cured at this time, only treated, because it never truly leaves our body. When children catch a viral infection, they simply wait for it to go away as well as possibly taking some extra medicine until it does. But HIV can still resurface even after treatment. According to Dr. Swanstrom, there are resting T cells in the body that have HIV but are not actively producing the virus. This group of cells is referred to as the

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Carolina Scientific viral reservoir and are a possible source of virus rebound if therapy is discontinued, but it is currently unknown precisely how to target these inert cells with the non-replicating virus.1,3 Dr. Swanstrom’s lab is interested in when and how the virus creates the reservoir. Other researchers have found that a group of these cells isolated from the body can be stimulated to replicate and produce the virus, demonstrating that the reservoir is “sitting there like a little time bomb.”1 While there is still ongoing debate on this topic, extensive research on viral reservoirs could hold valuable insight into the nature of the dormant disease.

The age-old battle between evolving pathogens and new drugs continues to this day. Even HIV medications will likely not be immune to this trend and “in the long term, we need to be prepared.”1 Dr. Swanstrom is studying a viral enzyme called protease that is essential to the life cycle of a virus. Viral proteases are responsible for cleaving precursor proteins at certain sites so that they can aid in virus replication (Figure 2).4 He describes how his team accidentally found HIV protease while studying another enzyme and how this fluke provided a new research path for his lab. The lab is collaborating with a team of drug design colleagues to find a protease inhibitor that binds to the protease active site, or the point where the proteins are cleaved. Dr. Swanstrom explained that “this binding will be the tightest, to the point where individual

health and medicine

genetic mutations in HIV will have no effect on the binding of inhibitor.”1 Protein cleavage by the protease is important in the virus’s life cycle; if the process does not proceed to completion, then that specific virus particle will be noninfectious.

Consequently, if this one step is blocked, the entire assembly of the virus shuts down.1 The only problem now is finding an inhibitor to block protease cleavage at a specific site without knowing how exactly it will work. Dr. Swanstrom and his team developed an assay that was used to screen over 700,000 compounds to find the ones that may block cleavage at the target site.1 This strategy could also be used to find other inhibitors that could block processing sites in other viruses.

Even so, these inhibitors will not lead to a cure because the dormant virus remains present in the body’s cells. The research that Dr. Swanstrom is performing will hopefully contribute to the understanding of the mechanisms HIV uses to evolve and reemerge after periods of dormancy. Protease inhibitors may be the first step in reducing the number of HIV outbreaks by shutting down viral machinery. The study of HIV leads to better understanding of specific molecular mechanisms that will be required to ultimately beat the virus.

References

1. Interview with Ronald Swanstrom, Ph.D. 02/09/17.

2. Arrildt, K. T. et al. J Virol. 2015, 89, 11294-11311.

3. Churchill, M. J; Deeks, S. G.; Margolis, D. M.; Siliciano, R. F.; Swanstrom, R. Nat. Rev. Microbiol. 2015, 14, 55-60.

4. Kurt Y. N.; Swanstrom, R.; Schiffer C. A. Trends Microbiol. 2016, 24, 547-557.

Figure 2 (top). Model of HIV Protease. Photo by MZeg [CC-BY-SA-4.0]. Figure 3 (bottom). Photo of HIV particles gathering at an infected macrophage. Photo by Liza Gross [CC-BY-2.5].

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health and medicine

SHINING THE SPOTLIGHT ON

ZIKA

BY GRANT PIEPLES Illustration by Tatihana Moreno

T

he coverage leading up to the 2016 Olympics in Rio brought images of hysteria around the Zika virus to our television screens. The serious implications of the disease invigorated research on how to combat its spread and quell its effects. Up until recent outbreaks, Zika virus was an obscure disease about which little was known. Presumably, the virus had been passed from animal to animal in the jungle, but the lack of human infection kept the disease out of the spotlight.

The large reports of disease in South and Central America and the confirmation of infection in Texas and South Florida have brought mainstream attention and increased funding to Zika research and the larger class of viruses to which it belongs: flaviviruses.

Flaviviruses are a set of genetically similar viruses transmitted by mosquitos and ticks that include West Nile virus and Dengue virus. It is this class of virus, with a focus on Zika, which Dr. Helen Lazear and her team in the Department of Microbiology and Immunology at UNC-Chapel Hill are working to better understand to fill the gap in Zika knowledge.

Zika is a unique member of the flaviviruses for a couple of reasons, including its ability to be transmitted sexually as well as through mosquitos.1 Additionally, Zika can cause birth defects, such Figure 1. Laboratory mice are as microcephaly (unusual used to study the effects of Zika. smallness of the head), Image courtesy of Wikimedia decreased brain tissue, Commons.

and limited joint and muscle movement, if a mother is carrying the disease while pregnant.1 Researchers are also investigating whether Zika could affect the development of the central nervous system.2 Dr. Lazear is focused on the viral and host factors that determine how Zika and other flaviviruses cause disease, meaning she studies the charDr. Helen Lazear acteristics of the virus itself and the cells it infects. Her research on these factors takes her in several directions. Dr. Lazear said these focuses include finding differences in the virus itself, in terms of the proteins it encodes, and how they interact with the host cell, discovering differences in the immune response by cells that are infected

by Zika that allow the virus to thrive in hosts, and uncovering the reasons that Zika is able to utilize abnormal types of transmission.1 The Lazear Lab employs various research methods to study its questions, the first of which is infecting cells in culture. There, they are able to test a variety of human cell types to see how Zika affects multiple parts of the body. They infect skin cells in order to see how the disease proliferates, immune system cells to track the effect of Zika on the immune response, and placental cells to study the birth defect aspect of the disease. By infecting cells in the laboratory, Dr. Lazear said they are able to “measure how well the virus infects, how well it replicates, and study the kinds of cellular immune responses that control viral replication.�1 This approach can be used to compare various strains of Zika to each other, as well as to other flaviviruses.

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health and medicine Figure 2. The main areas of the world affected by Zika. Image courtesy of Wikimedia Commons.

The Lazear Lab implements mouse models of disease to test other aspects of Zika. Dr. Lazear and her colleagues infect mice with Zika to see how quickly they become sick and how much the disease affects them. The use of mice allows Dr. Lazear to test the ability of the virus to spread into different tissues, including the ability of the virus to cross the bloodbrain barrier and infect the brain, its ability to affect the testes, placenta, and other tissues that are relevant to understanding the Zika disease in humans.1 The mouse models are used to test the roles of different parts of the immune response in controlling Zika. The Lazear Lab genetically alters mice to lack certain parts of their antiviral immune responses to effectively isolate others. By isolating certain aspects of the immune response, Dr. Lazear can see exactly what each aspect does in response to Zika, which is

important to consider when determining how to treat those who have been infected.

Studies done on mouse models by the Lazear Lab showed the effects of Zika on the mice, including weight loss within five days of infection and death within ten. They developed neurological disease signs such as weakness in the limbs and paralysis. Dr. Lazear found high concentrations of the virus in the brain and spinal cord, consistent with the congenital birth defects that the virus causes. There was also a high concentration of the virus in the testes of male mice demonstrating how the virus is sexually transmittable.3 Dr. Lazear’s research is geared towards understanding the basic biology of Zika virus. She said, “In order to provide better advice to say, pregnant women in families, or to think about different ways to combat the virus, you have to have an understanding of how it replicates, causes disease, and invades different tissues.”1 Understanding Zika will also help to understand and minimize the effects of future viruses that are not yet human pathogens. “A reason we want to understand the host species that are susceptible to infection by different flaviviruses is that this is an opportunity for the emergence of new pathogens and so, much like it’s important to understand how something like Zika virus can go from being an obscure virus that just transmitted in the jungle to something that’s a human pathogen, it’s important for understanding that about other flaviviruses as well,” Dr. Lazear said.1 This research is setting the groundwork for effective treatment and prevention for Zika and other flaviviruses. Dr. Lazear’s research is not only important for the treatment of Zika virus, but disease in general. Her research will shine the spotlight on the nature of Zika and other similarly obscure viruses to shape future knowledge and treatment of viral diseases.

References

1. Interview with Helen Lazear, Ph.D. 02/16/17.

2. Eppes, C.; Rac, M.; Suter, M. A.; Sanz, C.M.; Espinoza, J.; Seferovic, M. D.; Lee, W.; Mastrobattista, J.; Clark, S. L.; Dunn, J.; Versalovic, J.; Murray, K. O.; Hotez, P.; Belfort, M. A.; Aagaard, K. M. AJOG. 2017, 213, 209-225.

3. Lazear, H. M.; Govero, J.; Smith, A. M.; Platt, D. J.; Fernandez, E.; Miner, J. J.; Diamond, M.S. Cell Host and Microbe. 2016, 19, 720-730.

Figure 3. Cross-section drawing of Zika virus. Image courtesy of Wikimedia Commons.

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health and medicine

The Invisible Needle

By Jeremiah Hsu

I

magine being able to heal any cut or wound by guiding a handheld laser over it. For Star Trek fans, this idea may not seem novel. In fact, in the year 2369, this “dermal regenerator” was commonly used (Figure 1)! Such is the inspiration behind a professor at UNC Chapel Hill, Dr. David S. Lawrence. Dr. Lawrence explains, “as a scientist, you look at that and you say, wait a second. You can’t do that with a beam of light…that’s not possible…but it is. But then you have to think like a 24th century scientist”.1 However, Dr. Lawrence’s work addresses wounds deeper than superficial injuries. Dr. Lawrence and his team have successfully been able to use red blood cells as drug carriers and manually release the drugs at target specific locations through the use of infrared light.2 Eventually, Dr. Lawrence plans to incorporate his research into treatments involving toxic drugs, such as cancer therapy.

The usage of red blood cells as drug carriers is not a new discovery. However, Dr. Lawrence’s research enables control over where and when the drugs are released. Typically, a drug that is injected into the human body is desired to be cell permeable, allowing the drug to spread throughout the body and combat target sites. However, in the case of conven-

tional chemotherapy, the permeability of cells and exposure of the body to toxic chemicals result in the side effects of chemotherapy.

To combat this, Dr. Lawrence discovered that by covalently bonding drugs to Cobalamin (also known as vitamin B12) ,through a cobalt-carbon bond, prevents the drug from crossing red blood cell walls under regular conditions.2 Dr. David S. Lawrence The process of loading the red blood cells with drugs begins by taking a sample of red blood cells and placing them in a saline solution. The saline concentration is first lowered to cause the red blood cells to expand. The pores in the red blood cells are expanded to the point where the drug-Cobalamin complex can enter the red blood cells. After the red blood cells are loaded, the saline concentration is increased to seal up the red blood cells, trapping the drug-Cobalamin complex inside.2 The red blood cells are now ready to be injected back into the body.

Once inside the body, the red blood cells travel through the blood vessels until they reach their target site, whereupon they are exposed to a beam of infrared light. The infrared

Figure 1: Dermal regenerator using light beams to repair skin wounds in Star Trek: Voyager.3

Figure 2: A beam of infrared breaking the bond between the drug and Cobalamin. Courtesy of Dr. David S. Lawrence.

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health and medicine

beam cleaves the covalent bond between the drug and Cobalamin (Figure 2). This allows the drug to leave through the permeable red blood cell membrane and attack the target site, leaving behind the vitamin Cobalamin as a byproduct.

Dr. Lawrence compared blood vessels to “a highway throughout the body” and the red blood cells “as trucks convoying the drugs…and when they get to a site we are interested in treating, we then hit them with light and the truck unloads its cargo”.1 Dr. Lawrence and his team have already shown conclusive results in mice.

The drugs are marked with a fluorescent tag so they can be traced (Figure 3).2 The method of using a drug-Cobalamin complex has demonstrated that the drugs are successfully contained within the blood cells before reaching a target site.

Before proceeding to human tri- Figure 3: Before and after pictures of red blood cells containing fluorescent als, there are still questions and potential marked drugs and their exposure to infrared light. Courtesy of Dr. David S. challenges regarding the use of Cobala- Lawrence. min as an anchor for drugs. Although Dr. Lawrence’s research shows promise in is the limited exposure of the body to the drug’s toxicity. limiting the body’s exposure to toxic drugs, the local sites surThe goal is to eventually store several different types rounding a target site are still exposed to the drug. “This goes of drugs in the red blood cells when treating diseases such to the heart of what we’re trying to do here,” said Dr. Lawrence, as cancer. The drugs can be pre-assigned wavelengths such “and that is how spatially restricted the drug actually is.” In ad- that different wavelengths of infrared light will cause the redition, the effects of ambient light exposure have not yet been lease of their corresponding drugs. Furthermore, Dr. Lawrence determined. The next step, Dr. Lawrence suggested, could be believes localizing the site of drug exposure can cause tumor investigating changes in drug concentration levels between death at a faster rate while eliminating the serious side effects groups of injected mice kept in the dark versus being exposed of conventional chemotherapy.1 to sunlight. The results will confirm the effects on the drugs in From science fiction to real life applications, Dr. Lawpotential patients’ exposure to sunlight. rence’s research embraces the progressive and evolutionary Dr. Lawrence hopes that one day his research will be thinking of science. Dr. Lawrence has transformed science ficwidely available as a drug delivery method, particularly for tion into nonfiction. An avid Star Trek fan himself, perhaps Dr. toxic drugs currently prescribed for cancer and autoimmune Lawrence was right all along: “Star Trek is real.”1 system impaired patients. The greatest benefit to using red blood cells to deliver drugs in a timely and targeted manner while being able to release the drugs whenever and wherever References 1. Interview with David Lawrence, Ph.D. 02/24/17.

2. Hughes, R. M.; Marvin, C. M.; Rodgers, Z. L.; Ding, S.; Oien, N. P.; Smith, W. J.; Lawrence, D. S.; Angew. Chem.

Int. Ed. 2016, 55, 16080.

3. Shell, T. A.; Lawrence, D. S. Accounts of Chemical Research 2015, 48 (11), 2866-2874.

Figure 4: Illustration demonstrating a light frequency receiver corresponding to drug release.3

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