Carolina Scientific- Fall 2017 by Carolina Scientific

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Carolina Scientific

scıentıfic Fall 2017 | Volume 10 | Issue 1

Connecting With Our Roots —REVISITING A LOST SCIENCE— full story on 1 page 40

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scıentific 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 UNCChapel 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 Editors: At Carolina Scientific, we believe that scientific discoveries should be accessible to all. In this era of rapidly advancing technology, our ability to speak to new audiences has reached new heights. We’re excited to bring you Carolina Scientific’s tenth year anniversary issue, and hope that over these ten years, we’ve succeeded in our mission to share our passion for science and research with a broad audience. In this edition, explore diverse topics, from the exciting advancements in virtual reality (page 26) to cuttingedge treatments for Alzheimer’s Disease (page 22). Enjoy! - Aakash Mehta and Ami Shiddapur

on the cover Carol Ann McCormick is the curator of the UNC-Chapel Hill Herbarium. Her work seeks to expand the field of botany research through an extensive collection of plant specimens. Full story on page 40. Illustration by Meredith Emery.

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

Executive Board Editors-in-Chief Aakash Mehta Ami Shiddapur Managing Editor Lynde Wangler Design Editors Alexandra Corbett Esther Kwon Julianne Yuziuk Associate Editors Akshay Sankar Alexandra Corbett Hannah Jaggers Janet Yan Ricky Chen Sara Edwards Copy Editor Adesh Ranganna Treasurer Elizabeth Smith Publicity & Fundraising Chair Ricky Chen Online Content Manager Marwan Harwani Faculty Advisor Gidi Shemer, Ph.D. Contributors Illustrators Staff Writers James Chang John Barguti Zoha Durrani Adam Chinnasami Meredith Emery Haley Clapper Maddy Howell Jason Guo Lizzie Satkowiak Harrison Jacobs Laura Wiser Aubrey Knier Zhi-Wei Lin Janie Oberhauser Copy Staff Ami Patel Anna Arslan Kevin Ruoff Preethi Gowrishankar Erin Sanzone Jeremiah Hsu Andrew Se Kristen Hunt Aubrey Knier Sidharth Sirdeshmukh Kieran Patel Zarin Tabassum Alex Payne Alexandra Tribo Andrew Se Sophie Troyer Wenzhong Wang Jessica Wangler Wilfred Wong Yuting Xue Designers Coco Chang Lauren Sprouse

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contents Genetics

Technology and Innovation

Germline Immortality: Advancing the Future of Cancer Genetics Ami Patel

8 10

Mice to Medicine: Using Genetic Models to Develop Tomorrow’s Treatments

Good Graphics, Better Sound

A Fluid Partnership: Math and Biology Harrison Jacobs

Andrew Se

Growing Cells On Paper

Ethical Complexities of Revealing Genomic Findings

Secrets in the Stars: UNC Searches for Extraterrestrial Life

Sidharth Sirdeshmukh

Special Topics

Reshaping How We Think About Vaping

John Barguti

The Future of Medicine is Inside Us

Neuroscience Psychedelic Renaissance

Live Like We’re Dying

Protecting Our Neurons: The Fight Against Alzheimer’s Disease

Accessible Books For Special Needs Students Yuting Xue

Alexandra Tribo

Growing, and Going Back to Our Roots Aubrey Knier

Erin Sanzone

Janie Oberhauser

Tomorrow’s Scientists: Inspiring Females in STEM Jessica Wangler

Sophie Troyer

Rethink Your Thinking: STEM Students Thrive With Active Learning Haley Clapper

Fighting Cancer by Predicting Cell Fate Jason Guo

Zhi-Wei Lin

Kevin Ruoff

Health and Medicine

Adam Chinnasami

Decoding Alzheimer’s Disease Zarin Tabassum

Carolina Scientific Executive Board

Ami Shiddapur Editor-in-Chief

Aakash Mehta Editor-in-Chief

Gidi Shemer Faculty Advisor

Lynde Wangler Managing Editor

Adesh Ranganna Copy Editor

Elizabeth Smith Treasurer

Akshay Sankar Associate Editor

Janet Yan Associate Editor

Hannah Jaggers Associate Editor

Sara Edwards Associate Editor

Richard Chen Associate Editor & Publicity Chair

Alexandra Corbett Associate & Design Editor

Esther Kwon Design Editor

Julianne Yuziuk Design Editor

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Work for Carolina Scientific!

Carolina Scientific is always looking for staff writers, designers, and illustrators! 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 website carolinascientific.org

Illustration by Laura Wiser

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Germline Immortality: Advancing the Future of Cancer Genetics By Ami Patel

tal cells is vital to understanding the process in which germ cell immortality is achieved.3 Errors in cell replication, such as the bypass of senescence, or cell aging, causes cells to rapidly multiply with little to no regulation. This error in particular leads to rapid telomere shortening and results in cell death. Many tumors, however, are able to overcome this barrier by activating gene expresDr. Shawn Ahmed sion of telomerase, causing increased cell growth without cell death. This is true for 85 to 90 percent of tumors, but the remaining 10 to 15 percent of human tumors have no active telomerase. Instead, telomere sequence repeats are controlled by alternative lengthening of telomeres, or ALT.3 In his laboratory, Dr. Ahmed and his research team study telomeres and the processes related to them using 1 mm long nematodes known as Caenorhabditis elegans. C. elegans make for an interesting test subject because they could potentially provide insight into how many types of human cancers operate. These subjects are utilized because their abundant

ne of the greatest mysteries of life is the ability of a living germ cell to pass on its lineage for generations. In humans, egg and sperm cells develop from germline stem cells. Germline cells replicate and pass on information without ever breaking down and wearing away.1 These cells are different from the somatic cells that are found within the rest of our body, such as our heart, skin, and pancreatic cells. The key difference between germline cells and somatic cells is that over time, somatic cells give way to aging and deteriorate, whereas germline cells are able to proliferate for ages.2 Therefore, somatic cells are mortal, and germline cells are immortal. Dr. Shawn Ahmed is a member of the UNC Lineberger Cancer Research Center, and is also an assistant professor in the Biology department at UNC-Chapel Hill. Dr. Ahmedâ&#x20AC;&#x2122;s primary focus is germline immortality and how telomeres located in DNA sequences facilitate this eternal continuity. Telomeres are DNA sequences located at the ends of each DNA strand. They do not code for important genetic information, but are present to protect the ends of chromosomes. Telomerase is an enzyme that maintains these telomeres in germline cells. Somatic cells, on the other hand, do not contain telomerase. Therefore, somatic telomeres slowly erode and shorten in length. This eventually leads to cell aging and cell death. This difference in telomere regulation between mortal and immor-

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Figure 1. Comparison of C. elegans wildtype to mutants over multiple generations. Image courtesy of Dr. Ahmed these different mutant populations of C. elegans. Their most recent experiment found that a particular mutant of C. elegans, which could not produce telomerase, used ALT to maintain telomeres of normal length. This crucial finding depicted that telomerase-independent human tumors with normal telomere lengths may use ALT. Understanding this process further would allow researchers to have a better comprehension of the 10 to 15 percent of cancers that function without telomerase, and instead with ALT. Additionally, ALT is more frequently present in some tumors than others, displaying that other factors of the cellular environment may induce the ALT process.3 Dr. Ahmed’s further research regarding ALT could potentially aid in determining how these certain types of cancers arise and how to better treat them. When it comes to cancer, the most significant and frequently asked question is how to find the cure. However, finding the answer is not an easy task. Discovering a cure is quite complex, as a greater knowledge of how the specific cancer operates and functions is necessary to potentially treat it. Although many cancers possess similar biochemical pathways, there are others that utilize novel pathways. For instance, the way that one cancer operates may be completely distinct from another. For Dr. Ahmed’s study, he and his team specifically examine the disparity between telomerase-dependent cancers and ALT cancers. Therefore, Dr. Ahmed hopes that through his research regarding ALT in C. elegans, “we will be able to have a better understanding of heritability of some types of human diseases, and even figure out causality and how to treat even one disorder.”2 With Dr. Ahmed’s research, we could garner more information about germline immortality, one of life’s most immense mysteries.

amount of mutants indicates whether multiple pathways could be required to regenerate the immortal germline.3 Dr. Ahmed’s recent research concerns the use of ALT in

References

1. Smelick, C.; Ahmed, S. Ageing Research Reviews. 2005, 4, 67–82. 2. Interview with Shawn Ahmed, Ph.D. 10/06/2017. 3. Cheng, C.; Shtessel, L.; Brady, M.; Ahmed S. PNAS. 2012, 109(20),7805-7810.

Figure 2. C. Elegans. Images courtesy of Wikimedia Commons

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MICE TO MEDICINE:

Using Genetic Models to Develop Tomorrow’s Treatments

Figure 1. A common lab mouse, often used in research due to its short life span, high reproducibility, and easy manipulation. Image courtesy of Creative Commons

BY ANDREW SE

f you take a minute to observe someone’s physical features–height, hair color, eye color, and more–you will quickly realize how unequivocally unique they are. Chances are, none of the other 7.5 billion people in the world look exactly like them. Genetic diversity is largely responsible for each of their distinct physical features. However, many physiological processes are also dependent upon the unique combinations of DNA that make up each person. Similar to a person’s facial structure or vocal pitch, individual responses to viruses and pathogens can also vary as a result of genetic diversity. “For many of these pathogens, it’s very difficult to study responses directly in humans,” said Dr. Mark Heise, a professor in the UNC-Chapel Hill School of Medicine’s Department of Genetics. “My view is if we really want to understand how these viruses cause disease, we have to account for the genetic variation.”1 One of the most critical issues that has impacted researchers who are trying to understand the role of genetics in disease response is the inability to control for the numerous variables that exist within nature. There are disease variables, like the type of pathogen and lethality, and transmission variables, like exposure time and dosage. Finally, host variables like age, immune system strength, and resistance from previous exposure can impact disease progress. These variables all work synergistically to create unique disease responses. To control for these variables, many researchers turn to animal models that can reproduce the human disease process. Researchers often use single inbred mouse strains, in which all the derivative mice are genetically identical, as they offer

reproducible trials and control for underlying genetics. However, as Dr. Heise said, the artificiality of the environment and the removal of genetic diversity from the experiment “limits how well we can take this information back to a more diverse population, like humanity.”1 Researchers like Dr. Heise have responded to this dilemma by using animal models to recreate human diversity. He is one of many researchers working on the Collaborative Cross (CC), a mouse genetic reference population built to model genetically complex organisms like humans. The CC is a database comprised of diverse laboratory mice strains that

Dr. Mark T. Heise

Dr. Martin T. Ferris

Carolina Scientific researchers have crossbred and identified. These strains can be made available for other researchers to study different genotypic combinations and the effects of population diversity on phenotypic response. Since mice are easy to breed and manage, and are genetically similar to humans, they are wellsuited to serve as model organisms. Having access to a large population of genetically identifiable mice helps researchers tie observed disease phenotypes to specific genotypes, allowing them to formulate relationships among data from different experiments that are using the same reference population.2 With the introduction of highly genetically diverse CC mice, researchers are able to “[control] for viral dose, environment, and demographic variables…[and] focus on the role that host genetic variation plays.”3 Dr. Heise has lauded the significance of the CC’s development. Because researchers know the specific genes in the mouse populations, they can directly study how those genes impact disease susceptibility, immune response, and other aspects of the disease process.1 Dr. Martin Ferris, an assistant professor in the Department of Genetics, further explained that even when researchers could not identify the specific genes of a test population, they could identify the disease phenotypes that the mice are exhibiting and infer about similar human responses.1 In other words, the CC has allowed them to more accurately identify and study causal relationships and specific responses from diseases in mice that exhibit nearly the same responses as humans.

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new models, he would release them to other research groups for drug screening and the development of other therapeutic approaches.1 Since the Ebola epidemic, Dr. Heise and Dr. Ferris have continued working to identify human-representative mouse models for other pathogens, such as influenza, Chikungunya, and Zika viruses. In the future, their lab will be involved in several projects, which include the development of a genetic mapping structure, the identification and validation of models of drug development, and the long-term goal of being able to understand the role of genetic diversity in the disease responses of humans.

Figure 2. An ebola virus virion. Image courtesy of Cynthia Goldsmith/CDC As our world becomes increasingly interconnected, there will be a growing need to investigate the diseases and pathogens that affect human life. With top researchers here at UNC and across the world, there is little doubt that we are constantly getting closer to developing more precise, efficient, and effective treatments to keep the public healthy. Although complex in nature, the Collaborative Cross retains a relatively simple premise–to characterize mouse genomes to improve the understanding of causal relationships between genotypes and phenotypes. This will eventually facilitate the screening and implementation of more effective treatments among humans. Furthermore, the comprehensiveness of the CC offers a unique combination between organizational structure and professional cooperation. As Dr. Ferris said, “One of the most exciting things for me is that when we start these collaborations, you find all sorts of things that are interconnected in ways that you would have never thought of before.”1 While these researchers are constantly working together and striving to aid in the development of life-saving therapies, they are also slowly figuring out why the minute genetic differences between each of Earth’s 7.5 billion people change the way our bodies respond to nature.

References

Illustration by Laura Wiser

1. Interview with Mark T. Heise, Ph.D. and Martin T. Ferris, Ph.D. 10/03/17. 2. Churchill, G.A.; Airey, D.C.; Allayee, H. et al. Nat Genet. 2004, 36, 1133-1137. 3. Ferris, M.T.; Aylor, D.L.; Bottomly, D. et al. PLos Pathog. 2013, 9, e1003196. 4. NIAID renews 5-year grant for research on emerging viruses. http://sph.unc.edu/sph-news/niaid-renews5-year-grant-for-research-on-emerging-viruses/ (accessed October 3, 2017).

Dr. Heise’s and Dr. Ferris’s work with the CC has already seen extensive real-world application. In March 2014, the World Health Organization reported a major Ebola outbreak in West Africa, which prompted CC researchers to take action. During the peak of the Ebola outbreak, the CC was used to look for new models of Ebola virus-induced disease. Dr. Heise and Dr. Farris were able to identify certain mouse strains that were reproducing aspects of human disease better than the existing mouse models. Once one researcher identified those

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Illustration by James Chang

How Bad Could It Be? Ethical Complexities of Revealing Genomic Findings By Sidharth Sirdeshmukh

he human genome is the entire set of DNA which makes up each of us—it contains the genetic information essential to the activity of each cell and the entire organism. Sequencing the genome, or identifying the nucleotide base pairs that make up human DNA, was a mammoth task, involving researchers from universities and other scientific consortiums across the globe. This lengthy project was initiated in 1990 and completed in 2003.1 After the human genome was successfully sequence, Dr. Francis Collins declared that “the genomic era is now a reality.”2 The field of genomic research and genetic sequencing, as well as search for its societal applications, truly took off after the launch of the Human Genome Project. However, as DNA sequencing and analysis continues to improve, researchers are identifying new risks and challenges for patients and the medical community, leaving the long-term fate of its human application hanging in the balance. UNC-Chapel Hill’s Dr. Gail Henderson, a professor of social medicine and the Director of the Center for Genomics and Society, is one of the leaders in the field of genomic research. Dr. Henderson, along with colleagues from diverse clinical and social areas, is examining how patients make de-

cisions regarding revealing their genomic information. This involves understanding how finding disturbing information might affect patients emotionally, and how the benefits and risks of such insights should be managed.3 Until recently, Dr. Henderson was the Chair of the Department of Social Medicine at UNC. She rose to her position after many years of research focused within China, where she studied the transition away from their Maoist healthcare system. She specifically examined the working of hospitals and the healthcare system in China. Her interest in the community-wide effects of healthcare changes eventually led her to accept a major role at the Center for Genomics and Society at UNC-Chapel Hill, whose mission is to examine the ethical, legal and social implications (ELSI) of translating genomic research techniques into applications for patient and societal benefit.3 Dr. Henderson’s recent reDr. Gail Henderson search has examined issues such

Carolina Scientific as the likelihood and the process of obtaining false positives in the course of genomic sequencing, and how the language used to convey analysis of genomic analysis affects patients.3 Figure 1. Image Courtesy of UNC Center for Genomics and The largest project Dr. Henderson currently directs is Society. called GeneScreen, which is funded by the National Institutes of Health. The project involves meticulously interviewing patients to understand the positive and negative social consequences of screening, and how best to educate patients and families about particular genetic abnormalities and mutations.4 Dr. Henderson believes that the combination of fundamental biological sequencing with clinical epidemiological research methods is what is unique about GeneScreen. “That’s how you study this kind of thing. You don’t just go and ask the general population: if you’re a patient and you had a chance to learn this, would you want these actionable findings revealed? There is no way to theorize these results—you just have to go out and [conduct first-hand research]!”2 The GeneScreen study recruited researchers across diverse areas including medical genetics, medical anthropology, and cancer genetics.4 Patients who participate in GeneScreen have a panel of genes screened, identifying eleven rare conditions including cancers and cardiovascular problems. Patients with disease-causing genes identified can then follow up with their physician. The interesting part of GeneScreen is understanding how this information is used (or not used) by patients, and how they react to the insights they obtain.5 Dr. Henderson notes that patients remain fearful or unwilling to learn about any negative conditions identified in the screening. Dr. Henderson illustrated the complexities posed by such rare but devastating findings: “If that child has a mutation, then one of the parents may have it. And if one of the parents has it, [the parent] may die or get very sick. Therefore, we should tell the parents, even if the parent wouldn’t want to learn about these conditions to begin with.”3 The GeneScreen project at UNC has the potential to help develop an ideal way to communicate genomic findings, based on the extensive dataset that is being compiled. Many questions arise from Dr. Henderson’s research with GeneScreen, dilemmas posed by false positives, patient preferences for how information is communicated, and so on.6 Does the public understand and care about the ethical grey areas in the application of genomics? What kinds of consent must be obtained in translation and use of genomic data? How can patients be educated about such a rapidly evolving field so they can make choices guided by information rather than uncertainty?5 Striking a balance between providing beneficial insights to patients versus the many negative consequences of revealing information about their genetic makeup is crucial. If ethical and decision-making challenges were to be overcome, the promise of genomic sequencing could be unleashed, and this could truly be the genomic era. One field that could be immediately impacted is that of health insur-

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ance.3 It is Dr. Henderson’s belief that “if studies like GeneScreen were conducted on a larger population, we would be able to develop care plans for diseases before they manifested themselves. By finding diseases before they develop and preventing their occurrence, the patient as well as the [healthcare] system would hopefully benefit from savings in time, effort, and money”.3 In the next decades, even as doctors and researchers obtain greater understanding of the human genome, and we witness significant advancements in applications of genetic engineering, more complex ethical challenges will be unavoidable. Dr. Henderson and her colleagues at UNC are leading the way in uncovering these challenges and using their findings to educate physicians, public health professionals, and the general public on the best way forward.

Illustration by Laura Wiser

References

1. Overview of the Human Genome Project. https://www. genome.gov/12011238/an-overview-of-the-human-genomeproject (accessed October 9th, 2017). 2. Interview with Gail Henderson, Ph.D. 10/6/17. 3. Wolf, S.M; Amendola, L.M; Berg, J.S. et al. Genetics in Medicine. 2017. 4. Gene Screen: Project Summary. http://genomics.unc. edu/genomicsandsociety/GeneScreen.html (accessed October 15th, 2017). 5. CRISPR/Cas9 and Targeted Genome Editing. https:// www.neb.com/tools-and-resources/feature-articles/crisprcas9-and-targeted-genome-editing-a-new-era-in-molecular-biology (accessed October 15th, 2017). 6. Beall, Abigail. Genetically-modified humans. http:// www.wired.co.uk/article/crispr-cas9-technique-explained (accessed October 16th, 2017).

Illustration by Tatihana Moreno

health and medicine

RESHAPING HOW WE THINK ABOUT VAPING

BY JOHN BARGUTI

istory tends to repeat itself. Before the general surgeonâ&#x20AC;&#x2122;s warning in 1964, cigarettes were exceedingly in demand during the mid-1900s, with nearly 72% of the male population and 26% of the female population smoking cigarettes.1,2 Electronic cigarettes, better known as e-cigarettes, have suddenly become a phenomenon that is sweeping Americaâ&#x20AC;&#x2122;s youth. E-cigarettes were originally introduced to the market as a healthy alternative to cigarettes that could help smokers quit. However, recent FDA funded studies conducted at UNC-Chapel Hill have shown that e-cigarettes are not as safe as they were once presumed to be. At the Marsico Lung Institute, Dr. Mehmet Kesimer and his team were tasked with unveiling the potential health effects of ecigarette usage. His research centers around understanding the basic mechanisms that govern the lung, with a focus on innate immunity against diseases. The two areas of focus in the study were the effects of nicotine and the flavorings used in e-cigarettes. The notion that e-cigarettes are a safer alternative to tra-

ditional cigarettes stems from the idea that the vapors are less toxic than those of regular cigarettes. E-cigarettes do not contain most of the carcinogenic ingredients, such as tar, ammonia, and even arsenic, found in conventional cigarettes. Electronic cigarettes consist of a vehicle and a liquid that can be vaporized. The liquid consists of nicotine and some flavoring such as vanilla or cinnamon. The flavoring substances are approved by Dr. Mehmet Kesimer the FDA for ingestion into the stomach. When the flavorings are heated to several hundred degrees and the fumes are inhaled, however, the effects are not fully understood. Furthermore, novel reactions could oc-

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Figure 1. An e-cigarette. Image courtesy of Flickr Creative Commons.

Figure 3. A mass spectrometer used to analyze sputum samples. Image courtesy of John Barguti.

cur in the lungs that are unforeseen. Researchers predict that vaporizing these flavorings produces toxic aerosol fumes that negatively affect the lungs. In Dr. Kesimer’s study, three study groups were analyzed: those who never smoked (control group), those who smoked only cigarettes, and those who smoked cigarettes but switched to e-cigarettes for a period of time. Individuals only using e-cigarettes could not be included due to the novelty of the e-cigarette industry and lack of extended e-cigarette use. Sputum samples of test groups acquired through inhalation of saline mist were quantitatively analyzed using a mass spectrometer. Sputum, a mucous-like substance, contains fluid lining the airways and was utilized to observe changes in protein levels. To the surprise of the researchers, a new unforeseen trauma was found. Extremely high levels of neutrophil granulocytes were found in the lungs. Neutrophil granulocytes are immune cells recruited to the lung during inflammation situations. As a byproduct of their activation, an enzyme known as neutrophil elastase is released that damages tissue over time. This tissue damage leads to chronic obstructive pulmonary disease, also known as COPD. The damage caused

by electronic cigarettes was so shocking that after a blind examination of the results, team member Boris Reidel, stated “I thought the data for the e-cigarette participants was for the heavy smokers.”3

“Due to the alarming results of the study, physicians that would have recommended their patients to switch from cigarettes to e-cigarettes might be swayed from that decision in the future.” So what does all this mean for the future of electronic cigarettes—are they not a healthy alternative to smoking cigarettes? Boris Reidel predicts that the FDA will begin regulating what can be put into the e-cigarettes and start removing specific flavorings that can produce harmful fumes from the shelves of stores.3 Due to the alarming results of the study, physicians that would have recommended their patients to switch from cigarettes to e-cigarettes might be swayed from that decision in the future. As for participants that have only used e-cigarettes, individuals are not yet old enough nor been in the habit long enough for useful studies to be conducted. Researchers can only make assumptions based on the data for older study participants on how that could affect themselves. One main takeaway from this study for many undergraduate students here at UNC-Chapel Hill is that much like beliefs about cigarettes in the past, electronic cigarettes are not as benign as once thought.

References

Figure 2. Diagram depicting a regular airway versus one afflicted with COPD. Image courtesy of Wikimedia Creative Commons.

1. History of the Surgeon General’s Reports on Smoking and Health. https://www.cdc.gov/tobacco/data_statistics/ sgr/history/index.htm (accessed Oc-tober 8th, 2017). 2. Trends in smoking rates. http://www.tobaccoinaustralia. org.au/fandi/fandi/c16s2.htm (accessed October 8th, 2017). 3. Interview with Boris Reidel. 10/6/2017.

health and medicine

Fighting Cancer by Predicting Cell Fate Image courtesy of Creative Commons

BY JASON GUO

nlike many other organs, the skin has the ability to repair and regenerate itself. There are three layers to the skin that can regenerate: epidermis, dermis, and the subcutaneous tissue. But what if these layers were composed of multiple sublayers, and the cellular growth within these layers could better our understanding of cancer? This is the case with the epidermis. One layer of the epidermis, the deepest basal layer, is composed of a sheet of proliferative cells. Depending on how they divide, these cells can either move between layers or stay within their own layer. If a cell stays within its own layer upon division, this is termed symmetric division. Conversely, symmetric and oblique division involve the cell positioning its daughters between two different layers. When a cell in the basal layer divides in a symmetric fashion, it remains in its same sheetâ&#x20AC;&#x201D;the basal layer. However, when an asymmetric or oblique division occurs, one daughter cell is typically moved into the sheet above it to promote stratification. The research of Dr. Scott Williams, an assistant professor in the De-

Figure 1. Staining of DAPI (DNA Stain), K5 (Basal Cell Marker), and GFP (Green Fluorescent Protein) to show asymmetric (ACD) and symmetric (SCD) cellular divisions. Image courtesy of Dr. Scott Williams

partment of Pathology and Laboratory Medicine, has led him to believe that imbalances between symmetric and asymmetric divisions could contribute to cancer growth.1 The stem cells in the skin must balance their differentiation to prevent an abundance of symmetric divisions. Thus, asymmetric divisions are esDr. Scott Williams sential for the skin stem cells to maintain equilibrium. Similarly, an overabundance of symmetric divisions could lead to the pathological expansion of "cancer stem cells." Dr. Williams has studied the orientation of cellular divisions and their influences on epidermal development through mouse models for many years. His research focuses on how asymmetric cell divisions are controlled and how their orientation can affect cell fate choices. Furthermore, he is interested in how this cellular division pathway may lead to the progression of cancer. One of his hopes is to find a separate method to treat cancer through the effects asymmetric divisions may have on carcinogenesis.1 So what determines which type of division the cell undergoes? Dr. Williams is examining the protein that orients the spindles for cellular division, LGN, and the functions of its interacting proteins Par3, mInsc, and GÎąi3. The spindles segregate important cellular material to opposite ends of the cell, which plays a role in their division. In basal cells, LGN is typically found in the upper, or apical, region and is controlled by its interacting proteins, which allow the cell to divide asymmetrically (Figure 1).2 If LGN is either evenly distributed or absent, the cell undergoes symmetric division.2 However, loss of

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showed that mInsc and LGN are not as efficient in localizing to the upper region of the cell, and concluded his study of Par3 by demonstrating its role in asymmetric spindle orientation and cell division. Thus, Par3 is essential for orienting the spindles to promote symmetric divisions. Similar to mInsc, the removal of Par3 results in more oblique and symmetric divisions.2 Like mInsc and Par3, Gαi3 is another protein that interacts with LGN. When reducing levels of Gαi3, LGN either forms weak crescents at the upper region of the cell or does not localize at all.2 Division angles are also altered, as cell undergo more oblique and symmetric divisions when removing Gαi3 compared to mInsc and Par3.2 This may imply a greater importance for Gαi3 in recruiting LGN to the upper region of the cell.2 Studying the interaction of proteins like LGN, mInsc, Par3, and Gαi3 allows for a better grasp of the mechanisms behind spindle orientation in asymmetric divisions (Figure 3). These pathways are significant for furthering the underFigure 2. Staining of LGN and DAPI (DNA stain). LGN localized in the upper region of the cell allows for asymmetric divisions. Image courtesy of Dr. Scott Williams the LGN interacting proteins Par3, mInsc, and Gαi3 randomizes the division orientation.2 For instance, mInsc is a direct binding partner of LGN, so Dr. Williams hypothesized that LGN’s inefficiency to gather in the upper region of the cell in early term embryos was due to an insufficient amount of mInsc.2 Dr. Williams found that mInsc interacts with LGN to enhance asymmetric differentiation in the late term embryos, but not in the early term embryos.2 Without mInsc, more oblique and asymmetric divisions were observed.2 This mInsc study, along with previous work, strongly suggests that spindle orientation machinery is a primary tool for differentiation in late-term embryos.2 Dr. Williams was then interested in finding out what controls mInsc expression. Previous research has shown that Par3 is also found in the upper region of basal cells. By overexpressing mInsc and reducing levels of Par3, Dr. Williams

An overabundance of symmetric divisions could lead to the pathological expansion of "cancer stem cells."

Figure 3. Diagram of LGN interacting with proteins Par3, mInsc, and Gαi3 to promote asymmetric divisions primarily in late term embryos. The value after ‘E’ represents the age (in days) of the embryo. Image courtesy of Dr. Scott Williams standing of carcinogenesis. “We think switching the behavior from symmetric to asymmetric division is a way you can promote differentiation within tumors and make them more benign.”1 One of Dr. Williams’s major goals is to find pathways that promote differentiation, as well as drugs that target these pathways.1 Aside from asymmetric division and cancer, the Williams lab’s research interests include the oral epithelium and cleft palate. According to Dr. Williams, “directions are unpredictable, but we will always have an interest in asymmetric division—that is the common theme.”1

References

1. Interview with Scott Williams, Ph.D. 09/29/17. 2. Williams, S.E.; Ratliff, L.A.; Postiglione, M.P.; Knoblich, J.A.; Fuchs, E. 2014. Nature Cell Biol. 2014, 16(8), 758-769.

Image courtesy of Creative Commons

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The Future of Medicine is Inside Us By Sophie Troyer

hat if intestinal disease was controlled not only by genetics, but also food consumption and the type of bacteria supported by the intestinal environment? This line of thinking is becoming popular in research of the microbiome, or the combination of all microbes in the body, and gastrointestinal disease. People could potentially manage and prevent intestinal disease by adjusting their diet, and subsequently, the types of bacteria present in their gut. Dr. Janelle Arthur in the Department of Microbiology and Immunology at UNC-Chapel Hill is exploring how specific gut microbes can promote inflammation and fibrosis, which can in turn lead to cancer. However, not all microbes cause inflammation, and some microbes are essential to the body. Knowing which bacterial strains affect inflammation in addition to learning how to maintain an intestinal environment that promotes a healthy microbiota containing the helpful strains, would be invaluable to the treatment of inflammatory bowel diseases (IBD). IBD occurs most often in the intestines, causing lasting inflammation. An improper immune response triggers the inflammationâ&#x20AC;&#x201D;the exact cause of which is currently unknown.1 Researchers like Dr. Arthur suggest that microbes play a large

role in this response. Dr. Arthur became fascinated with how our genetics and diet could change our microbiota, and proposed that an altered, or unhealthy, microbiota could act on the body to influence health and disease.2 Initially, she wanted to research how diet and obesity could affect the microbiota and lead to cancer. However, her research interests changed when compelling data from a project using gnotobiotic (germ-free, but selectively colonized) mice revealed that certain gut microbes could promote cancer.2 That project led to research suggesting that inflammation alters the gut microbiota so that more of the harmful bacteria are present, leading Dr. Janelle Arthur to cancer promotion.3

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health and medicine

Figure 1. (left) Interaction between E. coli and epithelial cells in the colon. Image courtesy of Dr. Janelle Arthur Figure 2. (right) A fluorescent in situ hybridization that shows the location of the E. coli in the colon. The red is E. coli, and the blue is nuclei in host cells. The E. coli is observed associated with the mucosa, with the majority in the fecal stream. Image courtesy of Dr. Janelle Arthur

A better understanding of the intestinal microbe and host gene combinations could predict the risk for developing IBD-associated colorectal cancer.2 For example, colorectal cancer and IBD patients were more likely to harbor the pks+ Escherichia coli that produced the response Dr. Arthur observed in their microbiota.2 Pks+ E. coli differ from normal E. coli in that they produce colibactin, a genotoxin, which is essentially a small molecule that can damage host DNA in the cells that come into contact with it.2 If DNA is damaged enough, it can form mutations that lead to cancer. A normal human microbiota contains E. coli that are not harmful to the body, so only certain strains have the potential to cause negative effects. This is why it is so important to determine which bacterial strains are helpful and which are harmful. Prominent cancer biologists had previously proposed six hallmarks of cancer, and have since updated that count to eleven.2,4 These hallmarks are characteristics that cancer tends to exhibit, such as uncontrollable replication.4 Dr. Arthur believes that the microbiota is not a single hallmark of cancerrather, it likely influences all the hallmarks of cancer. This is significant because the microbiota can determine a patient’s responsiveness to cancer therapy.2,5 “Basically, the microbiota influences everything, we just have to find which bugs and in what context,” Dr. Arthur says.2 The next step for Dr. Arthur’s lab is to examine how exactly microbes influence inflammation and associated problems, such as cancer and fibrosis.2 Fibrosis is excess connective tissue that can form in a damaged area of tissue. Patients with IBD, especially Crohn’s patients, often develop fibrosis in addition to intestinal inflammation.2 There is no known cause or way to predict who will get fibrosis, and the primary treatment is to remove part of the intestine.2 The lab’s recent data suggests that inflammation-associated fibrosis is stimulated by a small molecule from bacteria in the microbiota.2 Now, the lab needs to determine how exactly the molecule promotes fibrosis, such as how it binds and what types of cells are involved.2 Additionally, the question of whether fibrosis is caused specifically by this molecule, or by similar molecules from the vast array of gut bacteria, remains.2 Part of the research on how microbes influence inflammation involves colonizing gnoto-

biotic mice with specific strains of E. coli and observing the interactions with the epithelial cells and mucosal lining of the colon (Figures 1 and 2). It is important to note the extent to which areas of the gut are inflamed or fibrotic for specific microbe and host gene combinations, because this tells the researchers how and where the effects are seen. The lab is also working on a new sequencing method to distinguish “genetically similar but functionally distinct” bacterial strains in the microbiota.2 This field is ever evolving, multidisciplinary, and often relies on new technology and methods. Luckily, rapid technological development means faster, cheaper, and more reliable data.2 Dr. Arthur explains, “It’s difficult because it’s hard to keep up with a rapidly evolving field that involves many disciplines. My work is a merger of immunology, microbiology, cancer biology, gastroenterology, and genomics/bioinformatics. It’s a lot of reading to do!”2 So why do Dr. Arthur and others in her field enjoy this research so much? “The clinical implications and the joy of doing cutting edge science. The microbiota is an ecosystem living inside of us and it contributes to nearly every aspect of health and disease.”2 The research that Dr. Arthur and others are doing on the diverse microbiomes of the body, whether in the intestines or beyond, is incredibly important for the future of medicine. It is necessary for doctors and patients to understand how treatments and diets can affect the microbes inside them, and how this can affect overall health. The answer to an expansive list of health conditions may lie in the ecosystem that has been inside us all along.

References

1. What is inflammatory bowel disease (IBD)? https://www. cdc.gov/ibd/what-is-IBD.htm. (accessed October 14, 2017). 2. Interview with Janelle Arthur, PhD. 10/6/17. 3. Arthur J, et al. Science 2012, 338(6103), 120-123. 4. Hanahan, D.; Weinberg, R.; Cell 2011, 144, 646-674. 5. Fulbright, L.E; Ellermann, M.; Arthur, J.C; PLoS Pathogens 2017, 13(9).

Image courtesy of Creative Commons

neuroscience

PSYCHEDELIC RENAISSANCE: A STRANGE TRIP INTO THE RESEARCH OF MIND-ALTERING DRUGS BY ALEXANDRA TRIBO

ithin the last decade, numerous studies have suggested that psychedelics, or psychoactive compounds that produce alterations in cognition and perception in humans, are able to deliver profound therapeutic effects to those suffering from various mental illnesses. The prototypical psychedelic, LSD, has successfully been used to alleviate treatment-resistant depression and bipolar disorder.1 Ayahuasca, a South American brew containing the hallucinogenic dimethyltryptamine (DMT), is being investigated for its potential to treat addiction, depression, and anxiety.2 MDMA, another psychedelic, will soon be used in Phase III clinical trials for the treatment of post-traumatic stress disorder (PTSD).3,4 Psilocybin, the psychoactive compound in Psilocybe mushrooms, has demonstrated great potential as a treatment for patients who struggle with smoking cessation, alcoholism, and cocaine dependence.4 Drugs once only known for their presence in recreational settings are developing a new reputation in the medical community. As both natural and synthetic hallucinogens rapidly gain the interest of scientists for their apparent role as a therapy for numerous neuropsychiatric disorders, there is no doubt that a psychedelic renaissance is underway. Dr. John McCorvy, working in Dr. Bryan Roth’s laboratory at UNC-Chapel Hill, is at the forefront of this rebirth. Dr. McCorvy is working to clarify the relationship between classical psychedelics and their binding sites in humans: the serotonin receptors (Figure 1). “I’m looking at what drugs are effective antidepressants and

what these have in common with psychedelics,” Dr. McCorvy explains. “We can use psychedelics as good probes to understand receptor function, and by doing so, we may be able to understand or even take out the therapeutic effects and encapsulate it into a new compound that other people can benefit from.”5 From an evolutionary standpoint, serotonin is a relatively old family of receptors that exist in almost all animals, including humans.⁶ Serotonin (5-HT) is the neurotransmitter that naturally binds to receptor proteins. 5-HT forms unique complexes with these receptors that initiate a variety of cel-

Dr. John McCorvy

Carolina Scientific lular and subsequent physiological changes. 5-HT and its correspondent receptors play crucial roles in learning, memory, mood, appetite, and thermoregulation.6 Their paramount function in mood regulation makes these receptors the targets for several antidepressants and antipsychotics. The 5-HT2A serotonin receptor subtype in particular is also the target for hallucinogenic drugs.⁶ Although this target receptor has been identified, the molecular mechanisms behind hallucinogenesis remain largely unclear. Dr. McCorvy is using an interdisciplinary approach to interpret how the chemical language of the ligand-receptor complex generates such a distinctive physiological effect. In early 2017, Dr. McCorvy, along with other members in Dr. Bryan Roth’s laboratory, published a breakthrough paper in Cell where they were able to crystallize the LSD-serotonin receptor complex for the first time. This feat allowed pharmacologists to view the orientation of LSD within the serotonin receptor, uncovering the key determinant that renders LSD so notoriously potent. The culprit, as it turns out, is extracellular loop 2 of the receptor.⁷ “When we saw the structure, we saw that extracellular loop 2 is clamping down on top of LSD, thus keeping it locked in. By mutating the loop, we found it actually reverses the long residence time on the receptor,” Dr. McCorvy says.⁵ Throughout this research, he also noticed something else about LSD that was interesting: when LSD is bound, the receptor stabilizes a specific pathway, the β-arrestin2 signaling pathway.⁷ Upon the realization of LSD’s ability to do this, Dr. McCorvy theorized that other serotonergic hallucinogens might share the same property. Finding a common denominator among classical psychedelics would be an invaluable step in fully understanding their pharmacology. Dr. McCorvy employs multiple different techniques to research the kinetic signatures of psychedelics and other ligands at serotonin receptors. It is a challenge to study these complexes and their signaling cascades because, as Dr. McCorvy notes, “you have to think not only as a biologist, but as a chemist—you have to understand the molecule just as much as you understand the receptor. It’s a nice marriage between the two.”⁵ Dr. McCorvy believes his work is extremely valuable, as getting closer to understanding how humans recognize drugs in the brain and tissues enables scientists to exploit the biological responses for further drug design. In the future, Dr. McCorvy plans to incorporate the use of neuronal cells into his research in order to study neuronal function and how serotonin receptors are an integral part to neuronal signaling. “We’d also like to start using transgenic mice and knocking out specific effectors, namely, β-arrestin2, which we find to be important for LSD’s effects, and try to study the behavioral effects that result from that," he says.⁵ Despite the resurgence of interest in psychedelics as therapeutics amongst scientists and the public alike, there is still a looming obstacle: multiple psychedelics are still classified as a Schedule I drug, designated as having no accepted medical use and a high potential for abuse per the Controlled Substance Act of 1970.⁸ In tandem with its scheduled status, psychedelic drugs widely possess a negative stigma, perhaps caused by the dissemination of anti-drug propaganda in the 1960s and 1970s. Even within the scientific community, psy-

neuroscience

Figure 2. Lysergic acid diethylamide (LSD) on blotter paper. Image courtesy of Wikimedia Commons chedelic research is a niche field of study often considered illegitimate. Acquiring funding for such research ventures is an enormous hindrance. Nevertheless, Dr. McCorvy daringly pushes onward, hoping that his research will lead to valuable additions to psychotherapeutic regimens and the understanding of cognition as a whole. He stresses that there needs to be constructive dialogue between members of the scientific community and the public because the rampant spreading of misinformation about psychedelics has stagnated progress in their understanding. Despite the common concerns for such substances, psychedelics have consistently shown that they are non-toxic, non-habit forming, and offer great promise as a powerful psychotherapeutic tool. The preliminary evidence is mounting. “I absolutely see a future where psychedelics can be used in a medical environment,” Dr. McCorvy says, “and if we can find a way to overcome a lot of the damage that society has put on us, even if through engaging in a mind-altering drug, then we can be better humans towards one another.”⁵

References

1. Nichols, D. E., Johnson, M. W., and Nichols, C. D. Clinical Pharmacology & Therapeutics. 2016, 101, 209-219. 2. Nunes A. A., Dos Santos R. G., Osório F. L., Sanches R. F., Crippa J. A., Hallak J. E. Journal of Psychoactive Drugs. 2016, 3, 195-205. 3. Kupferschmidt, K. All clear for the decisive trial of ecstasy in PTSD patients. Science Magazine. http://www. sciencemag.org/news/2017/08/all-clear-decisive-trial-ecstasy-ptsd-patients (accessed September 26th, 2017). 4. McClelland, M. The Psychedelic Miracle. Rolling Stone. http://www.rollingstone.com/culture/features/how-doctors-treat-mental-illness-with-psychedelic-drugs-w470673 (accessed September 26th, 2017). 5. Interview with John D. McCorvy, Ph.D. 9/26/2017. 6. Nichols, D.E. Pharmacology and Therapeutics. 2004, 101, 131-181. 7. Wacker, D., Wang, S. McCorvy, J.D., Betz, R. M., Venkatakrishnan, A. J., Levit, A., Lansu, K., Schools, Z. L., Che, T., Nichols, D. E., et al. Cell. 2017, 168, 377–389. 8. Jikomes, N. Worth the trip: psychedelics as an emerging tool for psychotherapy. http://sitn.hms.harvard.edu/ flash/2015/worth-the-trip-psychedelics-as-an-emergingtool-for-psychotherapy (accessed September 26th, 2017).

neuroscience

Illustration by Lizzie Satkowiak

LIVE LIKE WE’RE DYING BY ERIN SANZONE

our doctor gives you a sympathetic look. “You have stage 4 cancer.” Your heart stops beating, and you are suddenly gasping for air. Your world is slowly coming to an end and all you can think about is how terrible death will be. People worldwide are petrified of the notion of dying: when it will happen, where it will happen, and how it will happen. Necrophobia, the fear of dying, affects 68% of Americans across

Illustration by Maddy Howell

the country.1 However, a series of studies by UNC-Chapel Hill psychologist Dr. Kurt Gray found the converse: death is surprisingly more positive than people anticipate.2 Dr. Gray studies how human mind perception could explain people’s actions, such as support of homosexual marriage and belief in God. Mind perception also affects how humans view death. “When we imagine our emotions as we approach death, we think mostly of sadness and terror,” says Dr. Gray. “But it turns out that dying is less sad and terrifying than you think.”3 A team of psychologists at UNC embarked on a study to determine how people nearing death view the end. In Dr. Gray’s research, he had two studies comparing the thoughts of those facing imminent death to those who envisioned how they would feel as death approached. The first study analyzed blog posts of terminally ill patients. Dr. Gray and his team used Google to find blogs of those diagnosed with cancer or amyotrophic lateral sclerosis (ALS), both terminal illnesses. The team identified and filtered one hundred blogs by specific criteria: the person writing the blog had to be the one diagnosed, and the

author must have died while creating the blog, which they confirmed by locating obituaries. After filtering the blogs, a total of twenty-five Dr. Kurt Gray blogs were research objects. Simultaneously, Dr. Gray’s team asked forty-five healthy individuals to create a blog page pretending as if they had just been diagnosed with cancer.4 Dr. Gray and his team dissected the blogs and noted all positive affect words (e.g. happy, grateful) and negative affect words (e.g. scared, fearful). By analyzing the data, Dr. Gray determined several correlations. There was a significantly greater amount of negative affect words in the forecasters’ posts, as opposed to the patients’. Additionally, the terminally ill patients had a greater amount of positive affect words in their blogs, as opposed to the forecasters.4 The differences in the percentages

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Figure 1. Results from Study 1: percentages of positive- and negative-affect words used by the terminally ill patients and the nonpatient forecasters as coded by Linguistic Inquiry and Word Count. Image courtesy of Dr. Kurt Gray

Figure 2. Results from Study 2: percentage of positive- and negative-affect words used in the inmates’ last words, inmates’ poetry, and noninmates’ forecasts as coded by Linguistic Inquiry and Word Count. Image courtesy of Dr. Kurt Gray of positive and negative affect words showed that the posts of the healthy individuals feigning terminal illness were less positive than those who were ill. In fact, the final blog posts of terminally ill patients often expressed feelings of love and gratitude. The team discovered that terminally ill patients within 12 weeks from dying, “near death” patients, had the most positive words in each post and had fewer expressions of negativity, indicating death by a terminal illness is more positive than most imagine. To further explore the correlation between time to death and positivity, Dr. Gray conducted a second study, which compared the last words for in-

mates on death row, to their poetry, and to a test group’s anticipated last words. In the test group, 117 people composed their last words as if they were hypothetically found guilty of a crime punishable by death.3 After analyzing the last words of inmates, poems of inmates, and the test group’s last words, the researchers saw results that paralleled those of the first study. The test group’s last words notably contained more negative affect words and fewer positive affect words than the poems and last words of true inmates. Between the poems and last words of death-row inmates, the last words contained fewer negative words than the poems of inmates who had

neuroscience more time to live. The results showed that when death is very near (right before execution), people tended to be less negative and more accepting. In both studies, the forecasters’ and the test group’s writings contained more negative affect words. The UNC researchers were astounded with the results. Dr. Gray commented about the last words of the inmates: “I thought for sure those would be more negative, considering they were about to be executed, but they were all much happier than I had anticipated.”1 Overall, when people think about dying, they generally have a negative connotation. However, when faced with death, there is more positivity than most people anticipate. Dr. Gray and Amelia Goranson are interested in exploring the reasons as to why some people are content as death approaches. Largely, they have found that people accept death as inevitable as time approaches and come to peace with the idea of dying. Dr. Gray commented that reflection on religion and connection to friends and family during the final days led to more positivity upon death.3 Further research is forthcoming from the UNC Psychology Department to hopefully uncover the multifactorial nature of perceiving death. They also intend to perform future studies to see whether positivity also increases if people do not face a terminal illness, but instead die naturally at an old age. Lastly, the team hopes to analyze whether race, education, and religion play a role in the positivity and negativity of death.

References

1. Fear / Phobia Statistics – Statistic Brain. http://www.statisticbrain.com/ fear-phobia-statistics/ (accessed September 23, 2017). 2. Association for Psychological Science. Emotions expressed by the dying are unexpectedly positive. https://www.sciencedaily.com/ releases/2017/06/170601124022.htm (accessed September 28, 2017). 3. Interview with Kurt Gray, Ph.D. 09/07/17. 4. Goranson, A.; Ritter, R. S.; Waytz, A.; Norton, M. I.; Gray, K. Psychol. Sci. 2017, 28, 988–999.

Figure 1: Image of healthy neurons (red), dying neurons (green), and neural nuclei (blue). Image courtesy of Dr. Deshmukh

neuroscience

Protecting Our Neurons: The Fight Against Alzheimer’s Disease BY JANIE OBERHAUSER

hat do the brains of a five-year old and a 75-year old Alzheimer’s patient have that your brain does not? The answer lies in a tiny molecule called miR-29, which does not exist at all in a child’s brain and is markedly reduced in Alzheimer’s patients. In normal, healthy adults, miR-29 is present at 400 times the amount found in the brain of an Alzheimer’s patient.1 Until recently, the question of how the

Dr. Mohanish Deshmukh

healthy brain remains functional for the majority of our adult lives remained unanswered. “It’s such a simple question to ask, but actually, it has not been addressed,” adds Dr. Mohanish Deshmukh, a professor at the UNC-Chapel Hill’s School of Medicine.1 According to Dr. Deshmukh, neuroscientists tend to focus primarily on studying developing and deteriorating brains. However, Dr. Deshmukh’s lab has adopted a different approach. In order to understand why neurons in the brain die in neurodegenerative disorders, they hope to first understand what keeps them alive. Perhaps the conditions that enable the long lives of neurons can be used to restore them during disease.1 Neurons are unique in that they are members of a small category of cells in the human body that are extremely limited in their ability to regenerate when they become old or worn out. Once a neuron dies, it is exceedingly

difficult to replace; this is what makes Alzheimer’s and other diseases that target and destroy neurons so debilitating. Because Dr. Deshmukh initially specialized in studying the programmed death of normal bodily cells, he and his team approach the issue of neural degeneration with a unique appreciation for the ability of many neurons to last for the entire duration of a human lifetime. Dr. Deshmukh says, “We’ve been more impressed with the ability of neurons to survive than to die. Neurons actually don’t want to die. Neurons have sophisticated, amazing, and redundant mechanisms to stay alive.”1 These myriad built-in countermeasures are where miR-29 comes into play. In order to answer the question of what causes neural degeneration and how best to prevent it, Dr. Deshmukh’s lab established a three-step plan. First, they hoped to identify a molecule that is present at high levels in normal adult brains, but reduced in the brains of Al-

Carolina Scientific zheimer’s patients. A small non-coding microRNA molecule, called miR-29, emerged on their radar almost immediately. Prior research found the abundance of miR-29 to be reduced by 40-50% in patients with Alzheimer’s disease.1 The next step was to prove miR29’s importance in neural longevity, another criterion which the miR-29 molecule met. In trials preformed in the Deshmukh Lab, neurons exposed to miR-29 displayed a surprisingly high resiliency to stress.1 The presence of miR29 is also known to inhibit the build-up of Amyloid-β, a substance found in high quantities in the brains of Alzheimer’s patients.2 Therefore, the small RNA molecule served the dual purpose of promoting neural endurance and restricting known manifestations of neurodegeneration in Alzheimer’s patients. To further test the importance of miR-29 in the mature brain, the Deshmukh Lab bred test mice deficient in miR-29. Initially, these mouse models developed normally, exhibiting all the signs of a healthy, fully-functional brain. However, all the miR-29-deficient mice died upon reaching adulthood. MiR-29 was clearly necessary in the mature brains of the mice, and thus, pinpointing the exact role of the micro-RNA molecule for adult neurons became the Deshmukh Lab’s focus.1

We’ve been more impressed with the ability of neurons to survive than to die... Neurons have sophisticated, amazing, and redundant mechanisms to stay alive. The third step in the Deshmukh Lab’s investigation is to examine whether increasing levels of miR-29 in the brain can have a therapeutic benefit on mouse models with Alzheimer’s disease. Dr. Deshmukh and his team recently received a five-year, $2.6 million grant

neuroscience

Figure 2. Graphic of a healthy brain versus a brain with the neurodegeneration of an Alzheimer’s patient. Image courtesy of Wikimedia Commons from the National Institute on Aging to continue to explore “miR-29’s role in neurodegeneration and evaluate its therapeutic potential through the use of Alzheimer’s mouse models.”3 The university has recently expressed interest in increasing Alzheimer’s research on campus, and has funded several pilot grants.1 Dr. Deshmukh’s lab also received one of these grants, and he believes that the medical school’s burgeoning interest in neurodegeneration is important because there are currently no cures for Alzheimer’s. The number of people affected by this disease is expected to increase sharply in the United States and the rest of the world in the near future. As a higher percentage of the total population lives longer, old age will increase the risk of neurodegenerative disorders for a greater number of individuals, making the development of a cure imperative.3 However, Dr. Deshmukh warns that many obstacles stand in the way of the development of a viable treatment for Alzheimer’s. “We just don’t know if this strategy is going to work,” he says. “Some ideas work in mouse models and don’t translate into human studies. The biggest obstacle now is not knowing whether this is going to pan out or not. But that’s what scientists do.”1 If miR-29 proves to be a viable treatment option in human patients as well as mouse models, the team then faces the additional challenge of finding a reliable method of delivering miR-29 to the brain. Due to the lengthy list of complications researchers face, the number of treatment options on the market today for Alzheimer’s patients equates to a

grand total of zero.1 This lack of options for victims of Alzheimer’s and other neurodegenerative diseases is especially alarming in light of current statistics. The prevalence of neurological disease has proven to be a growing problem as the global average lifespan gradually crawls upward. According to Medical News Today, one in every three seniors develops Alzheimer’s or a different, similar degenerative neural disorder near the end of their lifetime. Currently, Alzheimer’s disease is the only entry featured on the list of the top 10 causes of death in the United States that does not have available treatment.2 However, if a degenerating brain can be restored through the study of a healthy one, perhaps that will change someday in the near future. The Deshmukh Lab’s previous research and newly-acquired grant certainly represent a step in the right direction.

References

1. Interview with Mohanish Deshmukh, PhD. 09/27/17. 2. MacGill, M. Alzheimer’s Disease: Causes, Symptoms and Treatments. https://www.medicalnewstoday.com/ articles/159442.php (accessed September 30, 2017). 3. Derewicz, M. NIH grant to help UNC researchers explore microRNA as route to Alzheimer’s therapy. https:// www.med.unc.edu/neuroscience/ about-us/news/nih-grant-to-helpunc-researchers-explore-micrornaas-route-to-alzheimer2019s-therapy (accessed September 30, 2017).

neuroscience

Decoding Alzheimer’s Disease BY ZARIN TABASSUM

Image courtesy of Creative Commons

espite the debilitating effects and prevalence of Alzheimer’s disease (AD), which affects 1 in 10 people over 65 years old, its pathology comes down to key proteins. Alzheimer’s patients have an abnormal buildup of protein structures called plaques and neurofibrillary tangles that lead to neuron death in the brain, but the mechanisms by which these protein aggregates develop is unknown. Dr. Todd Cohen from the Department of Neurology at the UNC-Chapel Hill’s School of Medicine is currently researching the mechanisms underlying AD. Dr. Cohen, along with many in the field, say that “if we can prevent the plaques and tangles from form-

Figure 1. Electron micrograph of tangle accumulation. Image courtesy of Dr. Cohen

ing, we can prevent the symptoms of Alzheimer’s Disease because the symptoms reflect the pathology.”1 New drugs that can target these proteins could be an effective treatment against AD. The Cohen Lab focuses on certain protein interactions that could be involved in the process of plaque and tangle Dr. Todd Cohen formation. The plaques are found outside of neurons and are composed of a protein called amyloid-beta; the buildup of these plaques causes protein aggregates termed neurofibrillary tangles within neurons. The tau protein is involved in the process of tangle formation inside the neuron (Figure 1). Dr. Cohen and his lab are interested in how plaques form outside neurons, and how they signal to the inside of the neuron to initiate tangle formation through the tau protein. “When those two things happen, and they start to accumulate as we age, that’s when you can get AD,” Dr. Cohen says.1 While there may be other genetic and environmental factors that could come into play, plaque and tangle accumulation is the main culprit behind AD. The lab uses a variety of techniques to uncover the exact mechanism(s) that results in the accumulation of tau and amyloid-beta. These techniques involve a combination of biochemistry and molecular biology to purify proteins and study

ons

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Figure 2. Stained micrograph of tangle accumulation. Image courtesy of Dr. Cohen their behavior. Dr. Cohen emphasizes the use of protein purification and the analysis of post-mortem human and mice AD cells.1 Dr. Cohen’s lab utilizes fast protein liquid chromatography, a technique that isolates proteins at high concentrations. Additionally, they employ antibody staining of brain tissue from AD patients and mouse models. This allows Dr. Cohen’s team to detect the presence of specific proteins and indicates where the protein can be found (Figure 2). These techniques are some examples of tools the lab uses to study the proteins involved in AD. Employing such methods has yielded promising results. For example, Dr. Cohen and his lab have discovered a post-translational modification (PTM) in the tau protein that causes the development of tangles. PTMs are chemical tags that allow proteins to navigate and communicate with their surrounding environment within a cell.2 Acetylation, which adds an acetyl group to the protein, is a PTM of tau protein that has been found to increase tangles in the brain. According to Dr. Cohen, this modification leads to loss of normal tau function, and the development of tangles, which could lead to neurodegeneration. Thus, the protein responsible for tau acetylation is a promising drug target.3

neuroscience

While the lab is making progress, drug discovery may take some time because the lab is still in the midst of clarifying the mechanisms involved in AD pathology. Dr. Cohen says it is difficult to make an effective drug for AD since “most drugs have not done well in Alzheimer’s disease for unknown reasons. It is difficult to reverse a process that has been snowballing over decades.”1 Even so, there is a drug called methylene blue that is currently in clinical trials because it could potentially prevent tau from producing tangles. The lab places more emphasis on producing tangles in different models, such as mice and cells, to understand why they form.1 Knowing the exact pathway could allow researchers to disrupt events that cause tangle or plaque formation. As a result, the lab could have the opportunity to develop preventative drugs. Studying AD comes with many challenges, as there are a lack of appropriate models to examine the disease, which takes decades to develop.1 The results from currently used animal and cell models do not always translate directly to humans. Additionally, most of the lab’s hypotheses are not correct, but according to Dr. Cohen, “this is a problem-solving field.”1 The lab must perform many experiments to get meaningful results. However, Dr. Cohen expresses optimism for future research since the field is “constantly moving forward and never going backward.”1 Even incremental advances lead the field closer to the truth. Dr. Cohen believes that AD is an addressable problem since Alzheimer’s is a two-part disease involving only two main proteins, amyloid-beta and tau.1 Disrupting these two proteins could ameliorate the disease. As more sophisticated techniques emerge in the future, the disease can be modeled accurately to deduce mechanisms behind plaque and tangle formation which will pave the way for new treatments.

References

1. Interview with Todd Cohen, Ph.D. 09/29/2017 2. Wander, C. Tau in Alzheimer’s Disease. http://tcohenlab. web.unc.edu/tau-mediated-neurodegeneration-ad/ (accessed October 1, 2017). 3. Irwin, D.J; Cohen, T.J; Grossman M.; Arnold, S.E; Xie, S.X; Lee, V.M; Trojanowski, J.Q. Brain 2012, 807-818.

“While there may be other genetic and environmental factors that could come into play, plaque and tangle accumulation is the main culprit behind AD.”

technology and innovation

GOOD GRAPHICS,

BETTER SOUND BY ADAM CHINNASAMI

Figure 1. Nick Rewkoski, an undergraduate researcher, demonstrating a demo of the team’s sound propagation. Image courtesy of Nick Rewkowski

irtual Reality (VR) is the future of entertainment. A myriad of new  technologies have been developed to immerse the user in fantastical environments. These technologies range from virtual reality headsets, such as the HTC Vive and Oculus Rift (Figure 2), to powerful game engines, such as Unreal Engine 4 and Unity. However, the current versions of virtual reality technolDr. Dinesh Manocha ogy have limitations. They require expensive and powerful graphics cards to generate high-fidelity images at full capacity. Body tracking, the computer’s ability to tell where a player is in the real world, is limited, as the displays have limited fields of view. Moreover, the generation of realistic sounds has been overlooked—until now. VR technology now includes simulation of sound propagation and use of signal processing methods to generate the final audio using multiple channels.  The current method of sound propagation includes different sounds for each movement of an object in the game environment.1 Therefore, a sound is generated depending on the player’s location and the obstacles in the environment, like a pillar or a moving door. For instance, if a boulder is rolling down a hill, sound artists will create different sounds for when the boulder first starts rolling, when it starts to get close to the player, and when the boulder is farther away bouncing down the bumpy hill. This method is not only inaccurate, but it is also extremely time intensive to develop because of the numerous sound files that need to be generated for each scenario. Dr. Dinesh Manocha, a distinguished professor of Computer Science, and his team have developed a groundbreaking method of generating sound in virtual environ-

ments. “Essentially, we apply the laws of physics to sound in virtual reality, and use mathematical models to tell the sound how to behave in a virtual world,” says Dr. Manocha.1 This allows realistic sound propagation with efficient computer processing unit (CPU) use, and it is much more accurate than traditional methods. For a moment, just listen to everything around you. Maybe you are procrastinating on studying for a test or are simply relaxing in your dorm. In either scenario, there is constant background noise. But, that background noise is constantly changing, such as people walking back and forth in a hallway or the air conditioning unit running noisily, and it is being diffracted off various objects such as chairs and walls. “All of these sounds are evolving, and they are impossible to replicate without adhering to the laws of physics because of unique sound properties,” states Dr. Manocha.1 Sound diffracts off objects, bends around corners, and even changes frequency in different mediums. Nevertheless, replicating accurate

Figure 2. The Oculus VR Headset. Image courtesy of Nick  Rewkowski

Carolina Scientific sound in a virtual environment is now possible due to extensive research from Dr. Manocha and his team. Furthermore, they have integrated their technology into current game engines.

Figure 3. One of the computers that runs the VR games. It has quite advanced hardware in order to run games smoothly. Image courtesy of Nick Rewkowski Dr. Manocha’s lab focuses most of their efforts on converting dry sound into a useable form of sound using convolution and signal processing methods. As part of his PhD dissertation, Carl Schissler developed many new and accurate propagation algorithms and a system called G-sound, which has been integrated with the Unreal game engine. “Gsound works in parallel with Unreal Engine 4 to produce quality sound; it allows us to put audio into games,” states Dr. Manocha.1 The first step of sound propagation is to study the objects with which the sound interacts. These objects are  specified  with three-dimensional modeling software, and advanced mathematical models are utilized to derive algorithms that tell the computer how to produce sound in regard to the specific objects in the area and the player’s relative location to those objects.2  However, there is one major caveat. Calculating these various algorithms produces a huge amount of stress on a computer’s CPU  (Figure 3).  Therefore,  computer scientists must create software code that enables the computer to process the information in an efficient manner.1 This allows the CPU to use fewer resources so that computers can handle larger sets of calculations than previously possible. “Though this seems fairly straightforward, years have been put into designing these algorithms,” says Dr. Manocha.1 These algorithms are even more complicated because they deal with sound, which is not as thoroughly researched as other aspects of virtual reality, such as graphics or visual rendering. Furthermore, sound algorithms have to work in conjunction with the graphics of the game. Most virtual reality games require technology with highly advanced graphical capabilities. This need is met with dedicated graphical processing units (GPUs) that are designed for the sole purpose of graphical rendering. Dr. Manocha and his team have the unique difficulty of trying to deal with generating audio that can be just as processing power intensive, but they are limited to a computer’s CPUs, which

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must also handle other tasks in addition to generating sound.1   Once the object has been mapped and the computer has analyzed the sound, one final step remains. The sound has to be added into the games. This is arguably the most important step, as this is what the player gets to experience. While at the lab, Nick Rewkowski, an undergraduate researcher, provided virtual reality demonstrations that incorporated the unique algorithms. The difference is quite dramatic. The sound gradually changes as you place an object in front of the sound source, and you can clearly hear the difference, as you duck behind a wall for cover in a firefight (Figure 1). Ultimately, this technology can improve the entire virtual reality experience, as sound makes the virtual reality experience truly lifelike. Inside a game, the visual experience is very important, but sound turns a good game into a phenomenal game. In fact, a majority of the most famous videogames have equally famous soundtracks, such as the Legend of Zelda and Halo.  Though virtual reality has a long way to go, Dr. Manocha and his team are very excited to see where the future will take them. The technology they develop will allow users to physically walk through worlds that have previously only been imagined.

Figure 4. (Top) Nick Rewkoski’s workspace. It is packed full of experimental tech and powerful computer equipment. (Bottom) Main area of the sound lab. Images courtesy of Nick Rewkowski

References

1. Interview with Dinesh Manocha, Ph.D. 10/2/17.  2. Schissler, C.; Manocha, D. Interactive 3D Graphics and Games 2016, 71-78.  3. Schissler, C.; Manocha, D. ACM Trans. Graph. 2016, 36, 1-12.

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—A Fluid Partnership—

Math and Biology By Harrison Jacobs

Image courtesy of Creative Commons

ow can a theoretical understanding of fluid dynamics apply to cancer research and drug development? At UNC-Chapel Hill’s Joint Fluids Lab, these are the types of questions that are being explored. From mathematical theory involving asymptotic analysis to experimental applications of jet turbulence and drug delivery, the Joint Fluids Lab combines seemingly different spectra of research to form an innovative and exciting place to work. The Fluids Lab contains a 120-foot-long modular wave tank, a wind tunnel, and a 3D stereoscopic imaging system among other devices.1 After applying mathematical and numerical simulations to model physical systems, the researchers of the lab apply their understanding to these devices and test their ideas. Dr. Richard McLaughlin was an original co-founder of the Joint Fluids Lab, along with Dr. Roberto Camassa. Dr. McLaughlin is an expert on how solute transport is affected by boundary shape, and determining optimal mixtures of plumes in jet stratification. To McLaughlin, the Dr. Richard McLaughlin best part of his work is the com-

Figure 1. Vortex ring descending as it goes through stratification. Image courtesy of Dr. McLaughlin bination of “performing experiments and developing theories to explain new phenomena, all while working with students and postdocs.”2 The unique nature of both theoretical and experimental techniques—combined with a wide array of modes of inquiry—is what truly separates the Fluids Lab from most conventional labs on campus. With the interdisciplinary nature of the experiments conducted in the lab comes an array of applications. In reference to biological systems, Dr. McLaughlin stated that the lab “recently published a series of papers on how, in solute transport, the geometry of the tube in which the solute is flowing can be used to control how it’s distributed as you

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While the high level of success that the lab has had in microfluidic research implies future success in similar research endeavors, McLaughlin says that the lab will continue to focus on multiple projects at a time. One such project, dealing with turbulent jets and stratification, has aeronautic applications. The project is connected to the formation of trapped oil plumes in the Gulf of Mexico oil spill during 2010.1 With this, the group developed some theory, and compared it with laboratory experiments to predict where and under what circumstances these plumes might form. Their work found that the rigorous mathematical results obtained establish the twolayer stratiﬁcation as being the optimal mixer over a class of suitably selected stable stratiﬁcations. These findings have applications with prior plume literature, but are limited to specific cases. The lab will continue its work in this area, but with more relevant oceanic applications.

References

1. Joint Applied Math and Marine Sciences Fluids Lab. http://fluidslab.web.unc.edu/ (Accessed September 25th, 2017). 2. Interview with McLaughlin, R. 9/21/17. 3. Aminian M; Bernardi F; Camassa R; Harris D; McLaughlin R. Science. 2016. 354(6317):1252-1256. 4. Camassa R; Lin Z; R McLaughlin; Mertens K; Tzou C; Walsh J; White B. J. Fluid Mech. 2016. 790(71–103).

Figure 2. Flow geometry of pipes. Image courtesy of Dr. McLaughlin push it downstream,” which has “applications in drug delivery, microfluidics, and chemical analysis done on small systems.”2 The Fluids Lab is continuing to explore further applications of their research in solute transportation. In their most recent paper, the Fluids Lab showed that a channel’s cross-sectional aspect ratio alone can control the shape of the concentration profile along the channel length. Thin channels deliver solutes arriving with sharp fronts and tapering tails, whereas thick channels produce the opposite effect.3 This discovery demonstrates the value of applying mathematical models, initially reserved for environmental and stratified fluid interactions, to biological systems.

NC STATE UNIVERSITY Interdisciplinary Physiology Graduate Program The Interdisciplinary Physiology Graduate Program at NC State University provides a wide-range of opportunities to help students reach their goals, whether they pertain to Biological Research or health-related professional school admission. The Physiology Graduate Program at NC State serves the pre-health population as an "academic enhancement" program. The ability to custom-tailor your degree program with courses that interest you and apply directly to your specific needs are part of what makes this graduate program unique and valuable in the current job market.

The unique nature of both theoretical and experimental techniques—combined with a wide array of modes of inquiry—is what truly separates the Fluids Lab from most conventional labs on campus.

The Physiology Graduate Program offers two different degrees:

• Master of Physiology, Non-Thesis Option • MS: Masters of Science (thesis-based) For a wonderfully detailed and informative explanation of Post-Baccalaureate Pre-Professional Programs, please see the following website:

physiology.grad.ncsu.edu

Illustration by Lizzie Satkowiak

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GROWING CELLS ON

PAPER By Zhi-Wei Lin

hat can you do with a piece of Whatman 105 Cleaning Tissue? To most laboratories, it is nothing more than a piece of tissue paper designed for cleaning lenses and other optical surfaces. In Dr. Matthew Lockett’s lab, however, this mundane material has the potential to change the way we culture cells. Currently, most cell-based assays rely on 2-dimensional (2D) monolayer cultures. In a 2D culture, cells are directly cultured onto a single flat surface often made from a thin plastic film. Several studies have found that cells on the flat surface have a vastly different morphology than those cultured in a 3D environment.1,2 Cells in 2D cultures even demonstrate less gene expression than those in 3D cultures.1 While 2D cultures are considered a standard practice among the scientific community for their simplicity and convenience, they do not accurately represent human tissue. This motivated Dr. Lockett to develop a 3D culture platform that is representative of human tissue for studying tumor invasion and drug resistance, as well as screening applications and techniques associated with the platform. This 3D culture platform is made with the humble Whatman 105 Cleaning Tissue, and it is nicknamed the “paper scaffold.” Paper scaffolds are versaDr. Matthew Lockett tile and can be tailored for differ-

ent types of study. For example, paper scaffolds can be used to screen endocrine disrupting chemicals, or EDCs. EDCs are chemicals that interfere with hormone synthesis and signaling, and they are prevalent throughout the environment. BPA, for example, is a known EDC often found in plastic bottles. Constant exposure to EDCs, even at a low concentration, has been implicated in the development of obesity, male and female reproductive problems, and hormone-sensitive cancers, such as breast cancer. Currently, only a handful of chemicals have been identified as EDCs. With more than 10,000 unidentified chemicals and new chemicals constantly entering the market, there is an urgent need for a high throughput screening method to quickly and accurately identify potential EDCs. Nathan Whitman, a Ph.D. candidate in Dr. Lockett’s lab, is currently leading the project on screening EDCs with paper scaffolds. This is done by culturing T47D-Kbluc cells, a breast cancer cell model, onto the paper scaffolds, which provide mechanical support for cells to form a 3D environment. When treated with estrogen or estrogen-like compounds, the T47DKbluc cells will express luciferase, an oxidative enzyme that emits light. Whitman is able to quantify the amount of luciferase production of each chemical. The readout is then compared to estradiol, a natural estrogen produced in the human body, to determine whether or not the chemical is a potential EDC. The reach of paper scaffold screens is significant when comparing it to other 3D cultures. These 3D cultures range anywhere from scaffold-based to scaffold-free. For example, in a scaffold-free magnetic levitation system, cells are cultured

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in hydrogel with iron oxide nanoparticles to stimulate a 3D environment. Other 3D cultures include microfluidic devices and hydrogel. In contrast to these types of 3D cultures, paper scaffolds are very inexpensive, easy to prepare and use, and do not require extended periods of culturing.2,3 More importantly, different assays can easily be adapted or combined to work with paper scaffolds. Paper scaffolds can be widely accessible to every lab and serve as a go-to platform for screening applications. Screening EDCs is only the tip of the iceberg regarding what paper scaffolds can do. Dr. Lockett is not only interested in screening potential environmental toxins, but also in answering the fundamental questions of how a microenvironment can promote aggressive tumor phenotypes. For example, a particular type of paper scaffold known as 9-zones can be stacked into multiple layers to study the invasion of cancerous cells under various oxygen conditions. To Dr. Lockett, the ultimate motive behind his work is to “use simple materials and ideas to tackle complex biological questions and problems.”4

References

Figure 1. Nathan Whitman carrying out an experiment in the hood. Photo courtesy of Dr. Lockett

1. Vantangoli, M.M., et al. PLoS One. 2015. 10(8), 1–20. 2. Ravi, M.; Ramesh, A.; Pattabhi, A. J. Cell. Physiol. 2017. 232, 2679-2697. 3. Kenney, R.M., et al. Chemical Communications. 2017. 53, 7194-7210. 4. Interview with Matthew R. Lockett, Ph.D. 10/07/16.

In contrast to these types of 3D cultures, paper scaffolds are very inexpensive, easy to prepare and use, and do not require extended periods of culturing... Paper scaffolds can be widely accessible to every lab and serve as a go-to platform for screening applications.

Image courtesy of Flickr Creative Commons

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SECRETS IN THE STARS: UNC SEARCHES FOR EXTRATERRESTRIAL LIFE

BY KEVIN RUOFF

oday, the belief that life exists beyond earth is stronger than ever.1 Just 25 years ago, we knew of fewer than ten planets, and now we are able to identify thousands within our galaxy—and that is only a small fraction of what remains to be discovered. Unlike locating stars, planets are significantly harder to find because they Dr. Nicholas Law are much smaller and dimmer. Methods for finding exoplanets (planets outside of our solar system) include the use of radial velocities, microlensing, and direct imaging. The simplest, most conceptual way of identifying exoplanets is by observing them as they cross in front of their host stars, dimming the stars’ luminosities by as little as 1%; the task is of astronomical proportions—literally. Astronomers from all over the world, including UNC-Chapel Hill, are working tirelessly to find exoplanets that can support life. Dr. Nick Law and his team here at UNC are pioneers in the development of new telescopes, and leaders in the search for exoplanets. Earth, for now, is the only planet known to fit the exact mold of what is required for life. Life is very sensitive; if a planet is too cold, too hot, without an atmosphere, without a magnetic field or orbiting a fiercely active star, its ability to sustain life will be disrupted.2 Dr. Law says, “When an astronomer says a potentially habitable world, what they really mean is there is a rock at the right distance from a star so that liquid water could exist on its surface, but you have to think about a lot more than that.”3 Another condition necessary for life is

the existence of an atmosphere that deflects harmful radiation from the host star. Additionally, the presence of life can be indicated by the presence of methane and chlorophyll. The first step in discovering if a planet is habitable is determining whether or not the planet is within the “goldilocks zone” where liquid water can form.2 These are the planets that Dr. Law is avidly looking for. One of two facets of research Dr. Law’s team focuses on is the detection of these planets by using UNC’s network of telescopes. Dr. Law emphasizes the need for versatility in a collection of telescopes. One of the main telescopes he uses, the Evryscope, is the first to use a gigapixel camera to capture the entire sky simultaneously.2 For reference, this is about 1,000 times the amount of information captured by a onemegapixel digital camera. The Evryscope is being used to look at the entire sky in the southern hemisphere, and a second Evryscope is currently in construction for the northern hemisphere. Each Evryscope has multiple cameras around a dome that rotates with the sky to observe a bigger picture of what is going on in space. When something happens (e.g., a supernova, a planet crosses in front of a star, a solar flare occurs, etc.) it might show up as a small change in an extremely large image from which not much information can be obtained.⁴ The next step is to use another set of telescopes, UNC’s Panchromatic Robotic Optical Monitoring and Polarimetry Telescopes (PROMPT), to get a closer look at the specific locations where something peculiar may have happened. Afterwards, UNC’s Southern Astrophysical Research (SOAR) and Southern African Large Telescopes (SALT) can capture an even more detailed and resolved image of what is going on in that part of the sky.⁵ These telescopes are not only used for UNC-specific projects, but also in collaboration with other research groups and organizations. For instance, NASA provided Dr. Law’s

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Figure 1. The Evryscope. Image courtesy of Dr. Nicholas Law group with surveys taken with their Kepler satellite to study any areas of interest captured with their equipment. Multiple studies are necessary to confirm observations as true because there are many false positives that go into these observations. For example, the dip in luminosity of stars could be caused by a number of things, not just a planetary blocking. This is very much a team project—and some of the most important members are the telescopes themselves. The coordinated operation of telescope networks in Chile, Australia, and South Africa involves the implementation of robust software to handle the amount of data collected. According to Dr. Law, 600 million luminosity measurements are taken every night to accumulate 360 gigabytes of data per night and 5 petabytes of data over the lifetime of a telescope.3 A lot of work goes into developing systems that can handle this data at an adequate pace. The telescopes operate on their own systems remotely controlled from UNC, and are visited only once every six months. They otherwise operate on their own, taking pictures of the sky and sending update emails every night to the project leaders. If there is a problem, the telescopes know how to handle the situation; they will either shut themselves down, or email the project leaders to ask for help. Since towns like Chapel Hill have atmospheric interferences, commotion, and light pollution, telescopes must be at remote sites. Places with favorable weather, high altitudes, and plenty of darkness are most optimal for making observations.3

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This kind of astronomical work is being conducted worldwide, but some of it is unique to UNC and specifically Dr. Law’s group. The Evryscope is a unique telescope designed and built at UNC—there’s no other telescope like it in the world. The exact layout of all its optimized cameras was designed by an undergraduate at UNC. One of Dr. Law’s graduate students is responsible for the entire mechanical design and construction blueprint of the Evryscope. Another graduate student led the largest ever survey confirming planet detections to determine whether or not the planets of NASA’s Kepler mission were habitable. Dr. Law says he personally wanted to come to UNC because. as he states, “I wanted to build the Evryscope, but I wanted to be able to follow up on those discoveries to figure out the astrophysics behind them.”3 Other programs at UNC focus on the building of telescopes or the interpretation of observations that other astronomers make. UNC also has a general-purpose network utilized in a large variety of projects, including the follow-up of Evryscope detections, attracting researchers like Dr. Law. The building of these telescope systems by Dr. Law and his group is truly an amazing feat. There is no guarantee that the amount of life in the universe rivals the Star Wars universe (not to mention, travel to these habitable planets is an obstacle in itself ), but optimism is on the rise. Humans have long thought they were alone in a tiny solar system, but our descendants may very well discover that they are only one of many intelligent lifeforms inhabiting an infinite universe. What we see in science fiction films could become a reality sooner than we think.

References

1. Osborne, H. SETI Astronomer Seth Shostak: We’ll Find Intelligent Alien Life Within 20 Years. http://www. newsweek.com/seti-seth-shostak-alien-life-discovered20-years-676301 (accessed October 15, 2017). 2. What Are the Requirements For Life To Arise And Survive? https://lco.global/spacebook/what-are-requirementslife-arise-and-survive/ (accessed October 15, 2017). 3. Interview with Nicholas M. Law, Ph.D. 09/26/2017 4. Evryscope. http://evryscope.astro.unc.edu/ (accessed October 2, 2017). 5. UNC Observatories. http://physics.unc.edu/researchpages/astronomy-and-astrophysics/unc-observatories/ (accessed October 15, 2017).

Dr. Law’s Group. Image courtesy of Dr. Nicholas Law

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Illustration by Zoha Durrani

rethink your thinking

BY HALEY CLAPPER

our heart races as you stare blankly before you. Time is running out, but you still have a long way to go. Thoughts clutter your mind and you frantically dig through them in hopes of finding the answer. You thought you had control, but you do not. You studied for this exam, yet, somehow, it was not enough. You have failed. Millions of students have experienced this panicked feeling during an exam because of a disconnect between their learning strategies and their academic performances. How do dedicated students receive failing grades or even fail their classes? Dr. Kelly Hogan, Associate Professor of Biology and Assistant Dean of Instructional Innovation at UNC–Chapel Hill, researches how the active learning approach encourages students in STEM fields to achieve higher levels of learning and, ultimately, success. Active learning is essentially the opposite of passive learning. Learning actively involves cognitive strategies such as writing, drawing, discussing, and explaining information to others. Learning passively consists mostly of memorization and merely listening to a lecture without engaging. "The goal of active learning is for students to take in information, process it, and demonstrate that they can do something with the information,” Dr. Hogan explains.1 She and several of her colleagues have shown that the active mode of education benefits students in immense and often unexpected ways. Dr. Hogan discovered her interest in active learning when she realized that the traditional style of lecturing contradicts basic cognitive science. Students do not learn most effectively when instructors relay all of the information themselves.

Instead, students learn best when instructors facilitate a structure that encourages participation, discussion, and problem solving from students of all backgrounds and learning styles. Among the active learning strategies that Dr. Hogan has implemented over the years, the “think-pairshare” method has proven to be an effective method for learning. First, the instructor poses a question to the enDr. Kelly A. Hogan tire class and allows students to think and answer individually. Next, students, in pairs or groups, discuss their thoughts and form responses together. After discussion, the instructor asks students to answer the same question again. Finally, pairs or groups of students share their responses and explain their reasoning to the class. Dr. Hogan notes that, unfortunately, the “think” portion of this strategy is frequently overlooked. Students often rush to discuss a problem without taking the time to collect their thoughts, write notes, and sketch diagrams or graphs to support their ideas. Allowing time for these crucial steps gives every student the opportunity to form a valuable contribution to the discussion. As a result, no one student will dominate and influence those who have not fully processed the information. To further discussion, Dr. Hogan

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“...a moderate course structure teaches students to allocate their time in a way more conducive to learning, encourages a collaborative classroom culture, and increases students’ valuation of the course.” poses questions that at least half of the students in the class likely cannot answer on their own. In addition to a deeper understanding of course material, students also gain an appreciation for a diversity of opinions and skills that they will use long after graduation. “This is professional development,” says Dr. Hogan. “You are not always going to agree with your co-workers, so you must find an answer that you each can own.”1 In a study conducted at UNC, Dr. Hogan implemented a moderate structure of learning in her introductory biology lectures. In contrast to a lower course structure—the traditional lecture—a moderate course structure includes elements such as guided reading questions, graded preparatory homework, and higher-thinking activities inside and outside of class.2 The study showed that a moderate course structure teaches students to allocate their time in a way more conducive to learning, encourages a collaborative classroom culture, and increases students’ valuation of the course.2 Dr. Hogan’s study revealed that students are more likely to prioritize coursework and engage with the material when cognitively challenging elements are established.2 Overall, the moderate course structure benefited students of all races, ethnicities, nationalities, and academic backgrounds by lowering failure rates significantly.2 Furthermore, Dr. Hogan found that underrepresented minorities and firstgeneration college students improved their learning skills disproportionately, closing the achievement gaps between these subpopulations and other, more advantaged students.2 Ad-

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ditionally, in the moderate course structure, disadvantaged students were more likely to participate in class because they felt less isolated from their peers.2 Disadvantaged students are typically unfamiliar with active learning prior to entering postsecondary institutions. As a result, these students find adjusting to a higher level of learning extremely difficult. “These students are in a different skill set where memorization is not all that they need — it is the base of what they need. Consequently, students struggle emotionally with their new identities,” Dr. Hogan remarks.1 Once students have practiced active learning, however, they thrive academically. To align prospective college students with higher learning, Dr. Hogan and other active learning advocates are working to extend their strategies to primary and secondary schools, as well as to community colleges. Teachers of all levels receive training on active learning and preparing their students for higher education more effectively. For example, in the summer of 2017, Dr. Hogan and other UNC faculty hosted an institute for STEM instructors to build upon their scientific teaching skills.1 Furthermore, Dr. Hogan suggests that students learn actively early on so that it becomes an innate way of thinking, almost like a second language. If all students learn actively from the beginning of their academic careers, education systems around the world could change drastically. In the future, Dr. Hogan hopes to see the active learning environment grow and become the norm for students in all fields and at all levels. By learning actively, students may no longer experience panicked feelings of unpreparedness and frustration and instead find confidence in their knowledge and abilities to learn.

References

1. Interview with Kelly A. Hogan, Ph.D. 09/28/17. 2. Eddy,S.L.; Hogan, K.A. CBE Life Sciences Education 2014, 13, 453-468.

Figure 1. An example of an introductory biology question asked using the “think-pairshare” method. The percentage of correct answers increased dramatically from before group discussion (left) to after group discussion (right). Image courtesy of Dr. Kelly A. Hogan

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Image courtesy of Wikimedia Commons

Tomorrow’s Scientists: Inspiring Females in STEM By Jessica Wangler

omen account for only 28.4% of those employed in scientific research and development in the world.1 Of the STEM (Science, Technology, Engineering, and Math) degrees earned in the United States, only 37% of degrees were obtained by women.1 In the past, the number of women involved in STEM was even lower–particularly prior to the boom of technological advancements made in the 21st century. There is a discrepancy between the participation and encouragement of women and men in the STEM fields. Many wonder why this is the case. UNC-Chapel Hill student Kimberly Bauduin, assistant director of Females Excelling More in Mathematics, Engineering, and Science (FEMMES), provides some insight into why this might be true. Her program is working to counter the lack of representation of women in STEM fields. FEMMES is a student-led organization of roughly seventy members. The group originated at Duke University in 2006, and expanded to UNC in 2008. The goal of FEMMES is to encourage young females, particularly those in fourth through sixth grade, to become interested in the sciences, and to stay involved as they ascend to higher levels of education. In Kimberly’s words, “If we can target sciences early, and show young girls that they have a place in STEM fields, that will be really impactful.”2 To encourage early participation of young

women in science, FEMMES runs an event in November each year which serves young women in the surrounding counties. Because the event is entirely free, female students of all socioeconomic backgrounds are encouraged to participate. The full-day FEMMES event in November consists of short activities, conducted with both professors and graduate students, and concludes with a capstone speaker. Kimberly reflected on her past experiences as a counselor, when one of the most popular short activities involved the science of making ice cream—a lesson, of course, that concluded with scoops of ice cream for everyone. Other activities included making cell models out of pipe cleaners and analyzing components of a virus in test tubes. These activities are performed with hopes of sparking young students’ interests in STEM fields. “I hope they take away the idea that there are so many ways they can see science in everyday life, and it can be applied to everything they do. We just hope their excitement will carry through to future academic studies.”3 Even years after the event has taken place, girls who participated still feel positively influenced by the lessons gathered from their experience with FEMMES. The directors even received a call from the mother of a participant who attended one of the first FEMMES events offered through UNC.

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Figure 1. The most recent FEMMES all-day event. Images courtesy of Jessica Wangler The mother reported that the girl was now in high school and was very interested in pursuing a career in marine biology. Reports such as this one not only cultivate hope for other young females but also help inspire volunteers. FEMMES offers positions to both graduate and undergraduate students alike. Undergraduate students can first become involved as counselors. After their first year as counselors, students can progress to administrative positions such as finance director or assistant director, which is Kimberlyâ&#x20AC;&#x2122;s current position. All undergraduate students are encouraged to apply for counselor positions, even if they are not majoring in any of the STEM fields. Kimberly herself is a business major. The directors of FEMMES are very excited for the event in 2018, which will mark the 10th year the program has been conducted at UNC. Each year, they have seen remarkable growth in the number of volunteers and participants in the program, as well as the amount of activities provided during their events. The expansion of FEMMES will encourage young women to stay interested and involved in areas not only in the STEM field, but also in other aspects of their lives where females are underrepresented. By supporting programs such as FEMMES, high-powered research schools such as UNC and Duke inspire young women to participate and contribute to research and advancements in the sciences.

References

1. Venessa. Women in Science, Technology, Engineering, and Mathematics (STEM) http://www.catalyst.org/knowledge/women-science-technology-engineering-and-mathematics-stem (accessed October 23, 2017). 2. Interview with Kimberly Bauduin. 10/03/17.

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ACCESSIBLE BOOKS FOR SPECIAL NEEDS STUDENTS BY YUTING XUE

lthough various institutions around the world have highlighted issues surrounding quality of life for disabled children, current efforts are still not enough. In addition to fulfilling children’s fundamental life requirements, such as financial support for expensive healthcare services, it is also important to be more solicitous regarding their menDr. Gary Bishop tal growth. This problem is most often addressed through access to educational resources, and has been a focal point of Dr. Gary Bishop’s work.1 Dr. Bishop, a professor of the Department of Computer Science at UNC-Chapel Hill, has been developing the Tar Heel Reader, an online program that helps students with disabilities learn to read independently. This project involves collaborative efforts from other professors in Computer Science and Education departments, as well as many undergraduate students. With the strong desire to help disabled students, especially those with physical and visual impairments, Dr. Bishop and several collaborators built this influential website. Tar Heel Reader is an online collection of free, easy-toread, and accessible books with a broad range of topics. The books are written by teachers and parents, with their final products published on the website and shared globally. Pic-

tures can be uploaded or selected from the vast collections on Flickr to make their works more interesting. Each book can be speech-enabled using multiple interfaces including touch screens, IntelliKeys software with customized overlays, and one to three switches.² These colorful picture books are composed not only of brief phrases such as, “I like dogs,” but also more advanced texts for elderly and disabled students. The website offers different page and text colors, audible voices from a man, woman, or child, and various sizes of page flip buttons. With the Tar Heel Reader, an older student learning to read can find a book with an interesting subject, while a student without the physical ability to turn pages can read like a normal child in a kindergarten or primary class. The Tar Heel Reader has now reached 10 million books read and is used in over 200 countries throughout the world. Its collection of 50,000 books has astonishingly outperformed professors’ early estimates of 1,000 books. Many of these books are even being read in countries that do not recognize English as their primary language. Dr. Bishop believes the website may be aiding some adults in foreign countries learn and practice English. Additionally, the Tar Heel Reader is being used as a research topic. “This is really nothing new here— it’s just nobody had done that before—so we did it,” said Dr. Bishop, slightly amazed by its significant impact.1 The project is impressive considering its prominent impact without the use of groundbreaking technologies.

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Figure 1. Tar Heel Reader Global Statistics. Image courtesy of Dr. Gary Bishop. Dr. Bishop and some undergraduate students are now working on new versions of Tar Heel Reader to make it more functional, interactive, and flexible for various student populations. The new Tar Heel Reader that Dr. Bishop is developing is definitely more sophisticated.1 To better support low-vision readers, this version of Tar Heel Reader can extend the font size up to four times larger than normal, and four page navigational styles are available (page-flip buttons vary). In the event that the picture shrinks because of larger letters, the alternate picture and text mode are created. The text-to-speech facilities are built into most modern browsers instead of the old technology used on the original site. It supports many more languages and sounds to provide a more natural interface compared to the monotonous electronic voice that was previously used. Additionally, speech pitch and rate can be adjusted to provide appropriate voices for different students. In the effort to form a more conversational and interactive reading environment for students, Dr. Bishop’s team is

“With the technology and availability of online libraries rocketing towards its peak, researchers are trying to synchronize the pace of human utilization and technological development.”

also working on another version of Tar Heel Reader with new functions that let teachers and parents participate in students’ reading processes. Four buttons are on each side bar of the book page, with each representing a brief comment (including “Like,” “Yes,” “I want to go,” etc.). Dr. Bishop wanted to help disabled students read just like normal kids with their parents sitting beside and guiding them. Furthermore, for teachers specifically, Tar Shared Heel Reader is being developed for group learning; teachers are allowed to categorize students into different groups regarding their reading levels, ages, and body conditions (visual or physical disability) by setting their files into the website and assigning them appropriate readings. This specific kind of technology aimed to help and service people with special needs is developing thanks to the kindness and intelligence of creators around the world. With the technology and availability of online libraries rocketing toward its peak, researchers are trying to synchronize the pace of human utilization and technological development. Through the efforts of Dr. Gary Bishop and his team to humanize this technology, its benefits have been disseminated to disabled students around the world.

References

1. Interview with Gary Bishop, Ph.D. 09/22/17 2. Tar Heel Reader. https://tarheelreader.org/ (accessed October 23, 2017).

Illustration by Meredith Emery

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Growing, and Going Back to Our Roots By Aubrey Knier

t the top of the stairs on the fourth floor of Coker Hall, you will find the North Carolina Botanical Garden’s hidden gem, tucked away in Room 401. Its cabinets overflow into the halls, full of the life’s work of brilliant scientists who have given the UNC Herbarium the reputation that it holds today. Home to nearly one million specimens, it is the second largest herbarium in the Southeast. Established in 1908, it has been loaning wildflowers, fossils, fungi, and algae to researchers

around the globe for nearly 100 years—and you can still feel the magical nostalgia of it all when you enter the room a century later.1 Until the 1970s, Carolina was considered a powerhouse of floristics (the study of plant species in a particular area) and taxonomy. However, as the herbarium aged, the support that it once had slowly withered away as a new science was entering the scene. Once molecular biology took off, the spotlight was turned to sequencing

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Figure 1. Herbarium specimens filed into cabinets. Image courtesy of Aubrey Knier

genomes and away from studying plant and flora specimens.2 Today, the UNC Herbarium is trying to bring that back full circle. The herbarium’s curator, Carol Ann McCormick, explains, “What we’re trying to encourage molecular biologists in the department to realize is that herbarium specimens are diversified, worldwide DNA waiting for them to use. We’re trying to change the perception of the scientists from ‘they’re just dead plants on paper’ to ‘oh, these are specimens from around the world that can be used in new and different ways’.”2 It is much easier to get the funding to sequence plants like rice, wheats, and other economically valuable crops. But those in the field argue that examining the DNA of all new species, even those without any known financial benefit, could result in breakthrough findings in the areas of conservation, agriculture and, namely, medicine. However, as technology advances and the cost of molecular analyses come down, McCormick is confident that the sequencing of more and more species will become increasingly realistic. Since botany has been overlooked in recent years, the herbarium is grateful that people are now wondering what the DNA sequences of these specimens may uncover. At least now the question is being asked, whereas 20 years ago it was not even considered.2 The herbarium hopes to open people’s eyes to the world of floristics that some wish they had found sooner—and with very good reason. Biodiversity is a popular topic in several biological fields, and McCormick believes that botanists are planted at the root of it. She emphasizes that "one of the big things people hear is: ‘biodiver-

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sity, biodiversity’—well, if you want biodiversity, you’ve got to know how many species there are, and you’ve got to train people to recognize it.”2 Encouraging the current and future generation of biologists and ecologists to acquire these skill sets are crucial to the future of science. “Learning how to identify and profile plants is not easy, just as learning to identify birds by ear is not easy—it takes practice, it takes dedication.”2 The role of botanists and ecologists in the future of science will become increasingly critical as the focus shifts back to floristics, so it is important that young students are being trained to eventually step into that role. The herbarium realizes that in order to educate, it must expand the availability of its specimens to the general population. While the herbarium has preserved nearly all of its traditional practices since its establishment, it now catalogues its specimens in a massive database shared with 300 other herbaria. Before the advent of relational databases in the late 1980s and early 1990s, there was no way to handle all of the information—but now, thanks to online cataloging, anyone can instantaneously search for species across the globe.2 This database is also important for recording and organizing the collections of retired faculty, which resolves an issue that the herbarium has been worried about for quite some time. For instance, Dr. William Coker, UNC’s renowned botanist and the namesake of Coker Hall, had an expansive collection that has earned botany at Carolina national recognition.1 However, the collection cannot be appreciated today in the way that it once was, simply because it is inaccessible. Carol McCormick explains, “Dr. Coker’s collection is legendary—it’s full of really good stuff but nobody knows what’s in there anymore. Everybody knew what he had in 1930, but after he died the collection has become randomized. We can’t find anything; everything is lost.”2 Faculty members of the herbarium are now comforted by the fact that in the future, researchers can log their collections in the database where it will be accessible long after they are gone. This technology will increase the availability of specimens across the globe, and provide opportunities for them to be studied in new and different ways. A change in administration has also contributed to the herbarium’s recent growth. Under UNC’s new chancellor, Carol Folt, the university is more involved in the

“The role of botanists and ecologists in the future of science will become increasingly critical as the focus shifts back to floristics, so it is important that young students are being trained to eventually step into that role.”

special topics herbarium now than in the last twenty years. Along with increased support comes big plans for expansion into a space nearly triple the size. After a year-long design process, the university plans to relocate the herbarium to the North Carolina Botanical Gardens farther south of campus, where it will have the capability to expand its collection from 1 million to nearly 2-3 million specimens. So, where will all new these specimens come from? Collections are too often forgotten or left without a home, and the UNC Herbarium’s goal is take in these orphaned specimens and add them to their collection. The staff’s fear is that other herbaria with limited support may be in danger of losing their specimens, and they want the capacity to give those orphaned collections a home. The adoption of these specimens has the potential to make UNC competitive with the largest herbaria in the country. However, McCormick remains humble. “Our goal is not to be the biggest, but it is to certainly be the best in the Southeast. We’re already the go-to herbarium for southeast flora, and we want to continue to be that.”2 With their determination to educate and their plans for massive expansion, the UNC Herbarium will definitely be making big waves in the scientific community—and who knows? It just may bring botany back as a major field of research.

References

1. Radford, L. The History of the Herbarium of UNC-CH. 1998,1-8. 2. Interview with Carol Ann McCormick. 9/27/17.

Figure 3. (Top) A snapshot of the process in sewing and mounting the plant specimens. (Middle) Detail of the UNC Herbarium’s specimen page. (Bottom) Helianthus glaucophyllus mounted on specimen paper. Images courtesy of Aubrey Knier

Figure 2. Dr. William Coker’s tribute inside of the UNC Herbarium. Image courtesy of Aubrey Knier

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TEN YEARS OF EXCELLENCE

For ten years, Carolina Scientific has provided the UNC student body with access to groundbreaking research. As the organization continues to grow, we would like to thank our Faculty Advisor, Dr. Gidi Shemer, for his continued support and mentorship.

“Somewhere, something incredible is waiting to be known.” - Carl Sagan

Image by Ildar Sagdejev, [CC-BY-SA-3.0].

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scıentıfic Fall 2017 Volume 10 | Issue 1

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.