scıentıfic Spring 2020 | Volume 12 | Issue 2
That Special Sense That Allows Turtles To Travel
—LOHMANN LAB LOOKS AT HOW TURTLES FIND THEIR WAY BACK HOME— full story on page 30 1
scÄąentÄąfic Spring 2020 | Volume 12 | Issue 2
U n iv e r s ity o f N o r th C a r o lin a - C h a p e l H ill
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Founded in Spring 2008, Carolina Scientific serves to educate undergraduates by focusing on the exciting innovations in science and current research that are taking place at UNC-Chapel Hill. Carolina Scientific strives to provide a way for students to discover and express their knowledge of new scientific advances, to encourage students to explore and report on the latest scientific research at UNC-Chapel Hill, and to educate and inform readers while promoting interest in science and research.
Letter from the Editors: In these troubling times when research is as important as ever, UNC still stands at the forefront of scientific research. Whether these advances be in medicine, physics, or ecology, we are proud to represent a university with such diverse and innovative research. Although this semester brought unexpected hardships, we hope this magazine gives you an escape into the multifaceted world of research and the exploration of scientific horizons. In this edition, you can explore UNC’s role in the fight against HIV (page 10-11), the struggle of economic access to necessary mental health treatments (page 18-19), and the effort to make solar cells more efficient (page 22-23). We hope you enjoy! -Sophie Troyer and Sidharth Sirdeshmukh
on the cover Illustration by Hannah Kennedy
Read on page thirty about the Lohmann’s dedicated efforts to learning about how sea turtles orient themselves to the Earth’s magnetic poles through a special instinct they possess.
Editors-in-Chief Sidharth Sirdeshmukh Sophie Troyer Managing Editor Andrew Se Design Editors Maia Sichitiu Associate Editors Aneesh Agarwal Divya Narayanan Copy Editor Divya Narayanan Faculty Advisor Gidi Shemer, Ph.D.
Contributors Staff Writers
Gillian Arleth Megan Butler Mehal Churiwal Harris Davis Rajee Ganesan Akankshya Jena Nisha Lingam Sneha Makhijani Jane Oberhauser Andrew Prevatte Aayush Purohit Sameer Rao Khushmi Shah Sam Shutt Diane Youngstrom
Cody Bollinger Megan Butler Maryann Bowyer Elizabeth Coletti Grave Reavis Stephen Thomas Wenzong Wang Designers
Ariana Dematti Jasmin Ferido Shriya Haravu Emma Kaeppler Yeajin (Sarah) Kim Abigail Shuman
Hanna Kennedy email@example.com www.carolinascientific.org facebook.com/CarolinaScientific @uncsci 4
Medicine and Health 6 8 10 12
Life Science 25
Genetics in The War Against Viruses Aayush Purohit
Waging War Against Malaria
Neuroimmunology: A Dialogue Between Two Crucial Systems Andrew Prevatte
In-Situ Forming Plants: The Key to HIV Prevention Jane Oberhauser
The Magnetic Map In Sea Turtles
Solving a Medical Mystery: The Math Behind Crohnâ€™s Disease
Exosomes as Drug Delivery Vehicles for Parkinsonâ€™s Disease Therapy
Protecting STEM Cells and Letting Them Free
A Cure for Cancer: How to Kill a Killer
Synthesis of Organic Products Inspired by Natural Compounds Sneha Makhijani
Psychology and Neuroscience 16 18
First Can Hurt: How First-Gen Neuro Students Face a Disadvantage
An Economic Evaluation of Severe Mental Health Disorder Treatment Options Gillian Arleth
Environmental Science 20
Modeling Innovation Patterns in Solar Technology Sameer Rao
What Causes Disease? Using Computational Biology to Understand Disease Origins
Closing the Gap: Using Conductive Polymers to Make More Efficient Solar Cells Harris Davis
Genetics in the War Against Viruses Aayush Purohit
Image courtesy of Creative Commons.
Viral infections pose immense threats to our with a virus, lymphocytic choriomeningitis virus health due to their resilient and lethal nature. As (LCMV). The viral infection causes symptoms such as antibiotic treatments are impossible, finding ways weight loss, elevated cytokines, thrombocytopenia, to slow down their attacks is essential. For example, and lung edema in mice, which are characteristics a group of viruses known as arenaviruses has been that resemble those found in humans suffering seen to have a devastating effect on populations. from an arenavirus infection. Conducting genetic Those diagnosed with an arenavirus infection face a studies using real diseases is easier and simpler high mortality rate of 50% in most cases.1 The work to conduct in mice, and their results have the of Dr. Jason Whitmire, an associate professor in the capability to be applicable to humans. Identifying a Genetics and Microbiology & Immunology depart- specific location, or locus, in the genetic makeup of the mice is a difficult task, but ments of the UNC School of Medicine, focuses on arenavi- “A specific region in the mice’s one that can show the region responsible for influencing the rus infections. Dr. Whitmire’s lab investigates viral infections DNA called the PL allele was seriousness and impact of the in order to try and analyze the observed to affect various disease.1 resulting immune responses For their experimentation, immune system features...” the researchers had to do a that they can provoke, as well as the mechanisms behind couple of different things in these responses, with one particular project of his order to put together the different pieces of the involving experimentation with mice as a model puzzle. They had to monitor the health, particularly for human pathology and examining genetics as it that of the immune system, of the mice as the disease relates to regulating the impact and mechanisms progressed through their system. Doing so meant of disease. Looking at the details of these systems that they looked at different symptoms and effects can reveal answers to questions that plague patient within the mice. The researchers proceeded to healthcare everywhere. conduct genetic tests to sequence the genes of these The Whitmire lab seeks to model arenaviruses infected mice. Analyzing the genetic information in particular. Arenaviruses, which are pathogens they acquired enabled them to see which regions that can lead to severe hemorrhagic disease, a and genes had been changed or altered. They rapid loss in blood with potentially fatal outcomes. could then highlight the specific regions possibly In order to accomplish the task, they infected mice responsible for changing the immune response
Figure 1: The severity of the disease dependis on the location of the chromosome as well as the location of the allele on that chromosome. Image courtesy of Mismumi et al.
of the mice and the overall outcome of the viral infection. Finally, through these genetic tests that looked at the sequence of DNA and comparisons of these results with the phenotypes (symptoms and characteristics which could be physically observed in the mice), the researchers were able to develop a few major conclusions. An initial result that stood out to the researchers was that the mice developed lethal hemorrhagic disease through their exposure in the lab to the LCMV infection, confirming their hypothesis. Moreover, a specific region in the mice’s DNA, the PL allele was observed to affect various immune system features by such actions as enhancing T cell response (contributes to the development of the disease), thrombocytopenia (deficiency of platelets which increases tissue bleeding), and lung edema (presence of excess fluid), all of which diminish host health. The PL allele was also found to specifically affect those genes that regulate immune system mechanisms from the chromosome 9 region, meaning that it could potentially speed up or slow down the rate at which the host would be able to fight off an attack from disease.1 Identifying this allele was a very important discovery because the allele can exist and be expressed in many different locations, but the researchers were able to use genotyping to find the location related to the outcome of the viral Dr. Jason Whitmire
infection. Dr. Whitmire plans to continue with this work by continuing to map different mutations in genes that can be associate with changes to the immune system, and thereby complete the bigger picture of how viruses can specifically target and weaken hosts. Ultimately, Dr. Whitmire’s research provides an interesting lens to see that even minor minute genetic differences in a host can extraordinarily change their health outcome. The analysis of the genetic makeup of mice has great potential in answering further questions concerning how genes and their differences can change the life course that viruses have and improve the immune response to such dangerous threats. Immunology is becoming an increasingly studied field of science because of its major applications and implications in a wide variety of areas related to improving human health and finding solutions to dealing with pathogens. Dr. Whitmire has done a lot of great work in his field, but still has plenty more to do, “the research is on the right path, but the important thing is to stick with it and to continue building on the foundation of knowledge and insight that has already been created.”2 If researchers are able to look at different studies in different fields and incorporate some of those ideas and concepts in their own studies, developing novel therapeutic solutions to combat viral threats will be easier than ever before. Figure 2: Lymphocytic choriomeningitis (LCMV). Image courtesy of the CDC.
1. Misumi I, Cook KD, Mitchell JE, Lund MM, Vick SC, Lee RH, Uchimura T, Bergmeier W, Mieczkowski P, de Villena FP-M, Ting JPY, Whitmire JK. (2019). Identification of a locus in mice that regulates the collateral damage and lethality of virus infection. Cell Rep. 27(5): 1387-1396. Doi: 10.1016/j. celrep.2019.04.004 2. Interview with Dr. Jason Whitmire, February 11, 2020.
Waging War Against Malaria Mehal Churiwal Dr. Boyce served as part of the infantry in South mapping the grounds, though, Dr. Boyce soon realKorea and Iraq before he came to UNC Chapel Hill ized that malaria as well as the geology and ecology and began medical school. After his second year of of the region share a close relationship, co-evolving medical school, though, he left to work as the Civil in an intricate and precise manner. His research Affairs Officer in Iraq where he was at the forefront thus follows the unique methodology of “looking of infrastructure development and other recon- for variation and mutations involved with drug restruction projects, interacting with local residents sistance to malaria in a small, concentrated area... to confront problems such as millions of people los- to understand heterogeneity in a micro-environing access to water in Baghdad city or having their ment.”2 sewer systems break down Dr. Boyce has worked in amidst the violence. He soon the Western region of Uganda returned to complete medifor about seven years, gathercal school with a newly found ing enormous quantities of inspiration to pursue public data on the specific biology of health. Now, Dr. Boyce’s whole the land and incidence of macareer is dedicated to fighting laria. One of the most recent this centuries-old battle in the and interesting topics has been 1 small, rural villages of Uganda. to understand variation in antimalarial drug resistance with When he started his rerespect to altitude in the highsearch on malaria in Uganda, land region of Western Uganda, there were no maps of the vilspecifically in the Bugoye sublages, and there was no way to county of the Kasese District. identify what areas had high or This is a particularly diverse low rates of malaria. Thus, he area of land for such a small rebegan his work walking around Figure 1: Map of the Bugoye gion, with steep hillsides towards the communities alongside residents, asking them where their subcounty in Kasese District, where the west and lower-lying ground the Bugoye Health Center is located. towards the east. The area is also village began and ended, often Image courtesy of Dr. Boyce. where the Bugoye Health Center receiving answers like, “Our village ends at that mango tree in the middle of the dirt is located, which is where the samples for this parroad.”2 Through the frustration and imperfection of ticular study were collected.3
are the furthest from public health centers, so they simply might have less access to AL and are thus less likely to acquire malaria resistant to AL.2 Another dimension to consider is socioeconomics. Unlike in the United States, living on the side of the mountain is not valued because it is harder to Dr. Ross Boyce grow crops there and one would have to walk farther to get water farther from town. When poverty’s contribution to the trend is considered, many possible influences are revealed, such as affordability of the same medical treatment, quality of housing facilities, access to appropriate transportation, and impact of proper nutrition.2 Finding malarial trends is a valuable and significant step forward in understanding the relationship between disease and community. However, more extensive research is required to eke out all the interacting variables before it is possible to confidently identify the mechanisms of such correlations. What is important to realize is that all of these factors – and many more yet to be uncovered – are likely contributing to the overall impact in some manner, and it is just a matter of how and to what extent. Dr. Boyce’s research underscores the value of having a narrow, focused lens and taking the time to understand the influences of micro variables to make a truly impactful transformation. As he said, “I have a career where I actually get a chance to try to make a difference in their lives and I get to ask interesting questions and I get to get some jobs and support people. So, I mean, I think I have the best job in the world.”2 References 1. Johnson, M. Bigger Picture: From Battlefield to Village, Ross Boyce ‘01 Wages War on Malaria. https://www.davidson.edu/news/2019/08/05/ bigger-picture-battlefield-village-ross-boyce-01wages-war-malaria (accessed February 2nd, 2020). 2. Interview with Ross M. Boyce, Ph.D. 01/31/20 3. Boyce, R. M.; Brazeau, N.; Fulton, T.; Hathaway, N.; Matte, M.; Ntaro, M.; Mulogo, E.; Juliano, J. J. Prevalence of Molecular Markers of Antimalarial Drug Resistance across Altitudinal Transmission Zones in Highland Western Uganda. The American Journal of Tropical Medicine and Hygiene 2019, 101, 799–802.
There were two main molecular markers analyzed in this study. A molecular marker is a specific mutation that indicates that the malaria is resistant to a corresponding treatment drug; thus, if a strain of malaria consists of a particular molecular marker, it cannot be cured with the corresponding drug. In this study, the first molecular marker tested was called the Plasmodium falciparum CQ resistance transporter (pfcrt) 76Tgene mutation, which indicates a form of malaria resistant to chloroquine (CQ). CQ used to be the most common, baseline treatment for uncomplicated malaria. However, due to the nearly universal development of CQ-resistant malaria, most treatment protocols switched to using artemether–lumefantrine (AL) in June of 2004. Thus, the second molecular marker tested in this study was called the Plasmodium falciparum multidrug resistance 1 (pfmdr1) Y184 mutation, which indicates a form of malaria resistant to AL.3 How does malaria acquire immunity towards a particular drug or medication? In general, each time a disease is transmitted and replicated from one person to another, there is a chance for a mutation in the disease to develop. Some mutations may be harmful and make the disease less potent, and some mutations may be neutral, having no lasting impact. Some mutations, though, could prove very helpful by providing the disease with immunity towards a certain drug. Consequently, the more frequently a disease is transmitted and replicated, the more mutations could occur, thereby increasing the disease’s chances of gaining immunity towards the current treatment. There was a significant inverse correlation between the presence of pfmdr1 Y184 mutations and altitude. The greatest incidence of pfmdr1 Y184 mutations occur in low-lying areas of the country while the lowest incidence was seen in high elevation areas. However, the study found no significant trend between the frequency of pfcrt 76T mutations with respect to elevation or river valley; the mutation was found fairly consistently between all the different samples across the area.3 As elevation increases, the air becomes cooler and there is less standing water, making it more difficult for the malaria-causing mosquitoes to live. Water runs downhill, indicating that runoff would accumulate towards the bottom to form pools of stagnant water. However, such a conclusion neglects all the other contributing factors. For instance, the trends in resistance may reflect the access to care available to the local population. As seen on the map, the health centers tend to be in areas of lower elevation; the areas of highest altitude in the west
In-Situ Forming Plants: The Key to HIV Prevention Jane Oberhauser By the end of 2018, an estimated 38 million people worldwide were living with HIV: a retrovirus that cripples its host’s immune system by subjecting it to a state of constant infection.1 The resulting condition, known as Acquired Immunodeficiency Syndrome, or AIDS, leaves the infected body vulnerable to a wide range of other infectious diseases and proves lethal if left untreated. Today, a daily, single tablet antiretroviral treatment regimen has replaced the cocktail of medications required to sustain life with HIV in the past. The focus of ongoing research has shifted from treating AIDS symptoms as they appear to preventing HIV infection in the first place. The effort begins with protecting the populations most at risk for contracting HIV. No viable HIV vaccine currently exists. As a result, protection comes in the form of a treatment known as preexposure prophylaxis, or PrEP. Clinical studies have demonstrated full protection from HIV infection for individuals who take PrEP daily: the same regimen required of those who have actually contracted the disease.2 However, adherence becomes a serious issue when prescribing a strict pattern of regular medication as a preventative measure for an otherwise healthy population. “If people have HIV, they know that they will die if they do not take the pill,” points out Dr. Martina Kovarova, an associate professor at UNC-Chapel Hill’s School of Medicine. “But for people who are healthy, taking the drug becomes more difficult.”2 Dr. Kovarova and a team of researchers from Gillings School of Global Public Health, the Eshelman School of Pharmacy, and the School of Medicine at UNC-Chapel Hill, along with the UNC-NC State Joint Department of Biomedical Engineering and Case Western Reserve University hope to improve PrEP adherence with the development of a long-acting, injectable drug delivery implant. Such an implant would eliminate the need for daily medication. Instead, patients would receive injections in 6-month cycles that would not need to
correspond with a pre-existing pattern of doctor’s visits.2 According to Dr. Kovarova, a pharmaceutical company, Viiv Healthcare, has already begun the clinical development of another long-acting injectable with a different formulation. This product, known as Cabotegravir involves the direct injection of a drug susDr. Martina Kovarova pension into the pa2 tient’s muscular tissue. However, this method comes with a serious disadvantage: once the injection is applied, there exists no mechanism for its removal. A lack of reversibility presents serious issues in instances of patient pregnancy or adverse reaction to treatment. With this type of intramuscular injection, traces of the long-acting formulation of the drug can linger in the body for up to a year after the discontinuation of PrEP treatment.2 As a result, the UNC group looks to take a different approach. “The system we have... is an injectable formulation that can be administered under the skin, and in a hydrophilic tissue environment it becomes solid,” Dr. Kovarova explains.2 This type of injectable is known as an in-situ forming implant, (ISFI).2 Using a process known as phase inversion, ISFI’s solidify only after injection into the body. The injectable formulation contains drug and biodegradable polymer dissolved in a biocompatible solvent. After solidification, implant releases the drug steadily over time as the polymer breaks down.2 Moreover, the injectable designed by the UNC group remains ultrasonically detectable beneath the skin while it dispenses the drug. As a result, patients may stop PrEP therapy at any time. Withdrawal from
represent a four-month improvement from the treatment windows offered injectables already in development.3 However, EFdA also presents a unique challenge. The drug is significantly more soluble than any other compound the group has previously formulated for a long-acting injectable.2 More soluble drugs tend to release faster from the solidified ISFI implant. As a result, Dr. Kovarova and the UNC group must find an EFdA composition capable of overcoming this problem.3 The grant also requires that the formulation be tested in two different animal models. Dr. Kovarova and the UNC group plan to first test the formulation in rats, which represent a preferred point of reference in clinical development. Once the injectable reaches a certain threshold of success in rat models, the group plans to proceed to testing in mini pigs, whose skin more closely resembles humans.2 The development of any drug in animal models presents the problem of translating results into predictions about human therapeutic outcomes. However, Dr. Kovarova remains optimistic that the UNC group will be able to innovate their way around any issues that might arise.2 The development of a long-acting in-situ injectable to replace PrEP in its tablet form would vastly improve the quality of life for individuals at risk for HIV. Such a formulation would cut down on the period during which a patient must adhere to a temporary tablet regimen after ceasing treatment by injection, and would improve the odds of patient adherence during treatment.2 Better protecting at-risk individuals from HIV infection would represent a significant step forward in the long-term effort to eradicate the HIV epidemic at its roots.
Figure 1: An illustration of the mechanisms behind in-situ phase inversion drug delivery implants. Image courtesy of Sheshala, R. et al. (2019) treatment requires only a simple scan and a small incision. This straightforward procedure stands to save individuals months of post-withdrawal adherence to a PrEP tablet regimen.2 The UNC group recently received a new threeyear, $2.91 million grant from the Bill and Melinda Gates Foundation for the formulation of the anti-HIV drug EFdA for an ISFI system.3 With low toxicity and high efficacy at low concentrations, EFdA represents the ideal drug for the long-term prevention of HIV transmission. An injectable ISFI system using EFdA could theoretically be used to sustain six months of controlled medication release. This timescale would
Figure 2: HIV infections in 2010 and 2016 by high-risk demographic group. Image courtesy of the CDC.
References 1. Global HIV & AIDS statistics - 2019 fact sheet. https://www.unaids.org/en/resources/factsheet (accessed Feb 11, 2020). 2. Interview with Martina Kovarova, PhD. 01/28/20. 3. Carolina awarded $2.91 million to create new ultra-long-acting HIV drug delivery implant: UNC-Chapel Hill. https://www.unc.edu/ posts/2019/11/06/carolina-awarded-2-91-million-to-create-new-ultra-long-acting-hiv-drugdelivery-implant/ (accessed Feb 11, 2020).
Solving A Medical Mystery: The Math Behind Crohn’s Disease Akankshya Jena Finding a cure for a disease is a seemingly insurmountable task. It is complicated enough that patients do not all have the same disease presentation or characteristics because of the diversity of their backgrounds. When considering environmental factors and genetics in the slew of possible causes, each patient now requires a unique treatment plan, from diagnosis to post-operative therapy (Figure 1). The scenario describes a wide range of complex diseases that, as one would expect, are too heterogenous to have an overarching cure. While biological research has made substantial contributions towards the cure of complex diseases, Dr. Terry Furey, a computational biologist in the UNC School of Medicine, approached the problem differently. In a world where technology has allowed scientists to collect more and more data, Dr. Furey recognized the growing importance of data in science and the need for computational analyses to translate it into applicable results. With this in mind, Dr. Furey decided to Dr. Terrence Furey combine statistics and genetics to study the heterogeneity of Crohn’s disease.1 Crohn’s disease (CD) falls under the umbrella of inflammatory bowel diseases (IBDs). IBDs are disorders resulting from abnormal immune system responses to intestinal bacteria, specifically in patients who are genetically predisposed to have the condition.2 CD is a chronic condition known for causing inflammation in the ileum and colon of the gastrointestinal (GI) tract (Figure 1). When foreign bacteria enter the GI tract, the immune system creates ulcers to combat and engulf the bacteria. In
Figure 1: Diagram of factors affecting origin and course of Crohn’s Disease. Image courtesy of Dr. Terrence Furey.
the case of CD, the immune system is unable to turn itself off, meaning the ulcers remain unless treated with medicine or surgery. Based on ulcer location, patients can experience a variety of symptoms, ranging from abdominal pain and diarrhea to loss of appetite and fatigue.3 IBDs have remained a medical mystery for decades because of their heterogeneity; no single treatment can be assumed to treat all forms of the disease, and genetic testing reveals little about onset or subsequent treatment plans. However, finding similarities among subtypes of the disease provides insight on treatment plans that cater to a certain group of patients who experience similar symptoms or develop similar associated diseases.4 Thus, Dr. Furey and his colleagues have investigated the possibility of associating genetic factors with the diverseness of CD. He uses a process known as genetic association analysis, which is essentially a statistical test that matches genotypical, or genetic, features with the expressed phenotypical,
Figure 2: Medical illustration of Crohn’s Disease. Image courtesy of Bruce Blaus [CC-BY-SA 4.0].
or physical, features of the patients.4 For instance, if the DNA of two patients contains the same nucleic acid sequence at a certain point—known as a loci— in their DNA strand and those patients exhibit similar symptoms of Crohn’s disease, then researchers could conclude that to be a match.1 To find more matches, Dr. Furey and his team used a series of methods to achieve accurate classification of CD. Initially, the researchers tested for general gene expression using biopsies from patients with and without CD. Results showed that the expressed genes of the CD patients were divided into two categories, one of which correlated with those of the non-IBD patients. Next, the researchers looked for differentially expressed genes, or genes expressed at statistically significant levels, between these two groups. They found genes affecting tissue-specific patterns at higher levels; for example, the groups had either ileum-specific or colon-specific genes regardless of where the cells were sampled from. Genes like CEACAM7 were found more often in colon-like samples, while APOA1 was found more abundantly in ileum-like samples.4 Based on these results, the researchers wanted to see how easily the cell could interact with its DNA, which would allow the cell to fundamentally change its cellular identity. A cell can respond differently to external factors based on what specific parts of its DNA sequence it uses to run itself. An ileum-like cell in a CD patient could easily respond to a certain treatment, while a colon-like cell may reject it. Dr. Furey and his team performed FAIRE-seq on all of the samples, which was a test to map the DNA regions where activity was occurring. It was found that colon-like and ileum-like samples both had increased activity in genes previously
associated with CD, indicating their correlation.4 To summarize, both assays support the hypothesis of two CD subtypes. The testing also confirms that the genomic effects of the cells arose internally, not due to external molecules or signals changing the cells. Aided with Dr. Furey’s recent work, researchers have been able to identify two subtypes of Crohn’s disease, specifically two distinct molecular signatures that correlate with distinct symptoms and subsequent treatment plans. Furthermore, these subtypes apply to individuals regardless of their age, status of treatment, or location of tissue sampling, which firmly supports the possibility of using genetic association analysis to distinguish affected individuals from those that are not. From here, options arise of detecting the disease earlier, confirming similar symptoms, and individualizing treatment. When applying the data clinically, testing patients for specific molecular signatures would allow for the creation of treatment subgroups, based on results showing that patients with colon-like CD were more likely to get a colectomy, while patients with ileum-like CD were more likely to develop ileum disease and would later need biological therapy.4 Using classification to treat CD, and IBDs in general, could prove to be an effective method. To improve and support the results from this paper, the researchers want to closely analyze the clinical journey of both adult and pediatric patients, and to study the corresponding tissue for each age group.4 Dr. Furey and his team aim to further such research to possibly find more specific subtypes of Crohn’s disease, and even apply this method to other complex diseases as well. It seems that, in a community heavily influenced by wet-lab research, math could be the key to providing answers that could shape the future of medicine.
References 1. Interview with Terrence Furey, Ph.D. 02/03/20 2. Center for Disease Control. Inflammatory Bowel Disease (IBD). https://www.cdc.gov/ibd/index.htm (accessed February 14th, 2020). 3. Baumgart, D.; Sandborn, W. The Lancet 2012, 380, 1590 – 1605. 4. Weiser, M.; Simon, J.M.; Kochar, B.; Tovar, A.; Israel, J.; Robinson, A.; Gipson, G.; Schaner, M.; Herfarth, H.; Sartor, R.; et al. Gut 2018, 67, 36 – 42.
Image courtesy of Creative Commons.
A Cure for Cancer: How to Kill a Killer Khushmi Shah
Cancer: the second leading cause of death in the United States. Even the sound of the word is feared. Imagine a world in which the disease is no longer an inevitable death sentence. At UNC-Chapel Hill, Dr. Andrew Wang’s lab strives to do exactly this. Dr. Wang received his M.D. from Harvard Medical School and is currently an Associate Professor and Director of Clinical and Translational Research in the Department of Radiation Oncology at UNC. He also co-directs the Carolina Cancer Nanotechnology Training Program. At the Wang Lab, researchers endeavor to apply nanotechnology to the development of cancer therapeutics in the form of drugs. The most recent major developments have been in boosting cancer immunotherapy, which is the body’s natural defense to fight cancer. Dr. Wang focuses his research on finding the most efficient ways to fight cancer. One of the primary therapeutic theories that caught his attention was the abscopal effect, which claims that when you treat something locally, you will see a similar effect on the whole body. For example, while radiation can be directed to destroy tumors Dr. Andrew Wang in a targeted region, its effect can also be seen throughout the rest of the body. About ten years ago, a new publication was released which described a patient receiving cancer immunotherapy as a treatment. While the patient responded initially, her body soon became resistant. As her metastasis progressed, she was given radiation to a tumor next to her spine that was giving her pain. “The re-
corded result was phenomenal, as not only the tumor disappeared, but all of the cancer in the woman’s body went away,” says Dr. Wang.1 This was the first major evidence of the abscopal effect and its efficiency. However, while the majority of tumors shrunk as a result of the treatment, Dr. Wang was compelled by the fact that some tumors still remained in the body. After reflection of the situation, Dr. Wang realized that he might be able to use nanoparticles to enhance the abscopal effect and advance cancer treatment. Using his prior knowledge from the field of nanomedicine, he developed an experiment that tested this question. Nanoparticles are microscopic particles that exist in the natural world but can also be created in a lab. One of their most important roles in medicine is their ability to carry drugs and participate in targeted therapy due to their unique structure. One can think of a nanoparticle as a sphere with unique chemical structural features that allow it to attach to specific targets. The Wang Lab is known for their use of nanotechnology and chemical engineering techniques to advance
Figure 1: Schematic drawing of the mechanism utilized by nanoparticles to capture tumor antigens. Image courtesy of Dr. Andrew Wang.
Carolina Scientific cancer research. For this particular study, Dr. Wang and his colleagues hypothesized that nanoparticles could be used to induce the abscopal effect and promote cancer immunity, as well as improve treatment response to immunotherapy. As seen in Figure 1, a tumor that is irradiated (radiotherapy) would first release antigens from the dying tumor cells.2 Ideally, these released proteins would be captured by the body’s immune cells. However, the released tumor proteins are not very stimulating and as a result are difficult for the cells to take up. As a result, Dr. Wang claimed that nanoparticles could be created to resemble viruses that are sticky and could capture antigens. The attachment of antigens to the nanoparticles would make the complex more visible to the immune cells in the body, making it easier for the tumor antigens to migrate to the draining lymph node.
of the greater visibility of the antigens due to them being attached to the nanoparticles, more antigens were taken up by dendritic (immune) cells and then drained out through the lymph node. The lymph nodes are structures in the human body that function as filters for foreign particles and cancer cells. Through these multiple studies, Dr. Wang and his colleagues were able to publish a paper proving how to develop efficient antigen-capturing nanoparticles that can improve cancer immunotherapy and induce the abscopal effect. Not only do the nanoparticles enhance the uptake of the cancerous tumor proteins, but they also cause an immune response throughout the entire body. The results of this study are “incredibly important for the advancement of personalized medicine,” claims Dr. Wang.1 This unique strategy exposes the immune system to various
Figure 2: Tumor growth curves of the mice treated with various nanoparticle. Image courtesy of Dr. Andrew Wang.
This can ultimately increase eradication rates and the abscopal effect in the body. Dr. Wang and his lab carried out various studies to determine the ideal structure of the nanoparticles that were the most effective in capturing the correct proteins. The different nanoparticles varied in their efficiency to capture antigens depending on their size and type of surface structures.2 PLGA and Mal nanoparticles were proven to be the most efficient in capturing the most protein, so they were used to further the experiment. Then, to test whether these nanoparticles could improve immunotherapy, the lab employed a mouse model. Mice bearing bilateral tumors underwent radiation and treatment on one side, while the other side was shielded from any radiation. It was seen that the nanoparticles were able to significantly improve immunotherapy and the abscopal effect, as seen in Figure 2, since tumor growth decreased.2 Another study was carried out to determine how the nanoparticles enhanced the efficacy of cancer immunotherapy. Rhodamine, which is a dye, was used to track the particles and their path in the body after radiotherapy. Because
proteins from tumors, which are specific to each person. After this amazing development in the field of medicine, Dr. Wang now hopes to make an impact on real people:. “I feel that if I want to truly measure myself and say that I made a difference, I need to make an impact. Clinically, I treat patients and I see an impact that way, but I’d like to actually see my research taken to a larger scale.”1 Dr. Wang already has a head start on his goals. In December of 2019, a startup company was launched whose purpose is to take the work done in lab and translate it to an actual product for use in clinic. This is just one of Dr. Wang’s many achievements, and there is a lot more to come from the Wang Lab. The future for cancer research is bright and on the verge of becoming even more efficient.
1. Interview with Andrew Wang, M.D. 01/31/20. 2. Min, Y.; Roche, K.C.; Tian, S.; Eblan, M.J.; McKinnon, K.P.; Caster, J.M.; Chai, S.; Herring, L.E.; Zhang, L.; Wang, A.Z.;, et al. Nat Nanotechnol. 2017, 12(9), 877–882.
First Can Hurt: How First-Gen Neuro Students Experience Disadvantage
Nisha Lingam Without a doubt, college provides new opportunities as well as new challenges and stresses to its students. However, depending on their background and their school’s characteristics, students may experience college differently, especially when it comes to academics. Some students might face different issues based on their background. To better understand the factors behind them, Dr. Monica Gaudier-Diaz Dr. Monica Gaudier-Diaz conducted her observational study on “Motivation, Belongingness, and Anxiety in Neuroscience Undergraduates,” with a focus on firstgeneration students. Dr. Gaudier-Diaz is a post-doctoral scholar in the Seeding Postdoctoral Innovators in Research and Education program, and currently works with Dr. Keely Muscatell at UNC-Chapel Hill’s Social Neuroscience & Health Lab. She is interested in the effects of stress on human physiology and psychology and neuroscience education, which is what led to her to concentrate on students majoring in neuroscience for her study. Considering the rising popularity of neuroscience programs in the U.S., she wanted to explore certain psychosocial factors that could result from university type and other demographics which may ultimately impact neuroscience majors’ academic success. More specifically, she focused on first-generation students, due to research on first-generation neuroscience majors being more uncommon and insightful to her field of study. “I’m really interested—as a minority student
Image courtesy of Creative Commons.
myself—in helping minority students do well in school,” Dr. Gaudier-Diaz says. “A lot of studies have shown that individuals from minority groups tend to have lower grades, and my idea is to understand why and what are the factors that we can target to help them overcome whatever difficulties they have.”1 More precisely, the three principal psychosocial factors studied were motivation levels regarding the goal of obtaining a neuroscience degree, sense of belongingness, and anxiety, all of which were measured using several different scales. Compiling these prevalidated questionnaires, Dr. Gaudier-Diaz and her team created an online survey to which 756 students responded, representing 69 universities across the U.S. The questionnaires evaluated the different aspects of the factors in question. For example, aspects of motivation included “expectancy (i.e., do they think they can do well in neuroscience courses?), value (i.e., do
Figure 1. Visual depiction of mediational analysis used to relate psychosocial factors to generation in college. Image courtesy of Dr. Monica Gaudier-Diaz.
In regards to challenges that came with the study, they want to do well in neuroscience coursework?), and cost (i.e., do they have the time, energy, and resources Dr. Gaudier-Diaz expressed her interest in obtaining to do well in neuroscience classes?).”2 To measure sense evidence of the body’s physical changes in response to of belongingness, two scales were used to gauge the psychological processes: “In other studies that we do in student’s opinion of themselves regarding their social our laboratory, we have participants come in the lab, we environment and how well they feel they belong. Trait examine inflammation in their blood and hormones in and test anxieties were investigated as well. The survey their saliva, so I would’ve loved to get some physiologialso contained questions regarding demographics, such cal markers of the population in this study.”1 In addition, as gender, and used GPA on a 4.0 scale as a measure of since there were no significant differences in the sense of belongingness based on generation in college, Dr. academic achievement. Afterwards, statistical analysis, including a media- Gaudier-Diaz also would have liked to study this factor tional analysis, was performed to obtain evidence of a in more detail. She mentions the challenge of acquircorrelation between generation and academic success, ing data from a representative population as only students from 69 of the 168 total as mediated by the tested universities offering neuroscipsychosocial factors: “Meence as a major responded to diational analysis allows the survey. Because the study you to explore how much has just introduced research of this correlation [beon first-generation students tween grade point average in the field of neuroscience, and generation in college] there is still much to investiis due to a third factor.” Dr. gate, including future research Gaudier-Diaz and her team on UNC students. found that test-anxiety, Nevertheless, the survey trait-anxiety, and default provided insightful data and motivation mediated the could lead to the development association.1 Essentially, default motivation (when of new intervention strategies the student lacks better directly focusing on anxiety options) became a speand motivation in firstImage courtesy of Creative Commons. cific factor in mediating generation students. Dr. academic success between first and continuing genera- Gaudier-Diaz’s research will certainly provide basis tion students, while differences in test and trait anxiety for gaining a better understanding of the factors that played similar roles in the medication of GPA and aca- affect first-generation students and will open doors demic success. for further study of factors mediated by other student Other statistical analysis methods indicated that characteristics including major, mental illness, and college type (National Liberal Arts College, National other demographics. To follow up on this study, she is University, Regional University, Regional College) partly continuing her research on anxiety through the study had an impact on motivation; students at Liberal Arts of psychosocial factors and physiological responses Colleges tended to place higher value on neuroscience to exam stress in UNC students. The study is currently coursework compared to those at National Universities. in the process of obtaining results by tracking stressAlthough gender differences were not predicted, related biological markers such as cortisol (in the saliva) they found that females tended to experience higher and inflammatory cytokines (in the blood), while also expectation-driven motivation, test-anxiety, trait- using questionnaires that gather data on psychosocial anxiety, and interest in succeeding in their neuroscience factors involved. Additionally, starting next semester, coursework. Most interestingly, they found that first- Dr. Gaudier-Diaz will be joining the teaching faculty in generation students experienced higher motivation the psychology and neuroscience department: “Now from not having a better substitute for their education that I am officially joining the department here, I’m path (also called default motivation), test-anxiety, and really interested in investigating whether these findings trait-anxiety in comparison to continuing-generation replicate among neuroscience students here. By tackling students who reported higher GPAs and experienced this problem, I will be able to help students.”1 higher expectation-driven motivation and personal/ References intellectual growth.2 “This data emphasizes that there 1. Interview with Monica M. Gaudier-Diaz, Ph.D. are psychosocial and academic differences based on 1/31/20. generation in college and suggests that by targeting 2. Gaudier-Diaz, M. M.; Sinisterra, M.; Muscatell, K. A.; these psychosocial factors we (i.e., educators) might be able to help students from underrepresented The Journal of Undergraduate Neuroscience Education backgrounds successfully complete their college 2019, 17(2), A145-A152. degree,” Dr. Gaudier-Diaz explains.1
An Economic Evaluation
of Severe Mental Health Disorder Treatment Options
Gillian Arleth Mental illnesses are more common than cancer, heart disease, and diabetes.1 Although they affect nearly one in five adults in the US, the question remains: are those suffering from mental illness effectively treated?2 Many researchers are evaluating the success of mental health treatment options, including UNC-Chapel Hill professor, Dr. Domino. Working in the Department of Health Policy and Management, Dr. Domino investigates the efficacy of healthcare policies that focus on low income and disabled populations. It wasn’t until college that she found her interest in health policy. Originally a piano performance major, she began taking courses in health policy and realized her true interests. In graduate school, Dr. Domino worked with mental health policies and economics. She has continued researching mental health economics and recently investigated the efficacy of primary care based medical homes in her article titled Through the Looking Glass: Estimating Effects of Medical Homes for People with Severe Mental Illness. Her review analyzes the impact of enhancements added to primary care facilities on those with severe mental illnesses. Dr. Domino states “In a primary care based medical home, a team maintains overall responsibility for an individual’s health care, including any coordination needed with specialty providers”.3 Medical homes have the potential to improve outcomes for patients with severe mental illness. These facilities are characterized by more communication between physicians and mental health care
providers, the development of understanding and trusting relationships between patients and caregivers, and patients are more likely to adhere to medication recommendations. Dr. Domino saw the need for more research to determine if these are actual advantages especially because of the Dr. Marisa Domino diversity in responses to treatment. She also recognized the significance of this research because mental illness disproportionately impacts people on Medicaid. Attentively monitoring treatment options could have far reaching impacts on the large portion of the population affected by mental disorders. The study focused on the effect of medical homes on patients enrolled in Medicaid and diagnosed with one of three different severe mental illnesses: schizophrenia, bipolar disorder, and major depressive disorder. Dr. Domino chose both schizophrenia and bipolar disorder because of their characterization as severe mental health disorders. However, opinions differ in regards to major depressive disorder’s similar categorization. Dr. Domino chose to investigate major depressive disorder because of the abundant evidence relating
Figure 1: The study showed an increase in medication adherence for all three groups. Image courtesy of Creative Commons.
the disorder to inability to hold a job and worsening personal relationships. The sample included those diagnosed with a severe mental health disorder who were not dual-enrolled in Medicare or a nursing home. 4 The study revealed positive associations between patient residence at medical homes and access to primary care along with specialty mental health care, increased medication adherence, and a slight decrease in emergency department use. These results were consistent across the three disorders. Emergency department models revealed that visits were more frequent in months prior to enrollment, and during the first month after enrollment. Medication adherence also shows a shift after the first month of being enrolled in a medical home. The data indicates lower levels of medication adherence during months prior to enrollment, while consequently, an increase in adherence was observed in the first month receiving treatment at the medical home. While there are clearly many benefits of medical homes, the drawback of higher Medicaid expenditures remains. Data reveals that Medicaid costs for patients enrolled in medical homes are estimated to be 27-37 percent higher than the non-enrolled control group. The use of medical homes and preventative screenings in individuals with major depressive disorder were associated. However, no association was found for patients with schizophrenia or bipolar disorder. Dr. Domino offers a possible explanation by speculating that major depression is a very common diagnosis, so primary care providers are more comfortable and experienced in treating them. The increase in treatment experience could be the reason why the patients with a major depressive disorder are receiving more preventative screenings which could be associated with a higher quality of care. The fact that preventive screenings were not equal across the disorders speaks to another important aspect of Dr. Dominoâ€™s research:
heterogeneity. Heterogeneity refers to different sources of variation which in this study could be different responses to treatment or different types of treatment received. Dr. Domino opines that this indicates that medical homes could tailor their services based on the patient and their level of psychiatric functioning. Recently, Dr. Domino has expanded on her research and investigates the effectiveness of policy changes happening right here in North Carolina. The Medicaid system in North Carolina is currently undergoing transformations once again. The changes will put into place managed care plans to help direct individualized care for those with Medicaid. Dr. Domino is working with the state to evaluate this transformation in the Medicaid program. She is also working on research investigating patient-centered medical homes for care by looking into accountable care organizations and creating financial mechanisms to improve quality, as well as, reduce costs. Dr. Dominoâ€™s research marks her as a pioneer in the medical field as it is critical to continuously evaluate treatment options for disorders that are so ubiquitous. By continuing this research, she is finding more ways to assess the effectiveness of health care policies put in place to help underrepresented populations. References 1. (nd) Mental Illnesses Are More Common Than the Big Three https://www.comphc.org/yakima-valley-mentalhealth-blog-detail.php?blog_id=5 (accessed February 5th, 2020). 2. (nd) National Institute of Mental Health https:// www.nimh.nih.gov/health/statistics/mental-illness. shtml (accessed February 5th, 2020). 3. Domino, M. E; Kilany, M; Wells, R; Morrissey, J. P. HSR. 2016, 52(5), 1858-1800. https://www.ncbi.nlm. nih.gov/pmc/articles/PMC5583299/ 4. Interview with Marisa E. Domino, Ph.D. 02/03/20.
Figure 2: 4.5% of all U.S adults are diagnosed with a severe mental illness. Image courtesy of Creative Commons
Modeling Innovation Patterns in Solar Technology By Sameer Rao Complete darkness. The year is 2030 and the the efficiency at which a solar cell converts sunlight United States power grid is no better than it was in into usable energy, reported in recognized test labs 2020. However, there are now Perovskite solar pan- and compared them to the values reported in sciels on the roof. In a flash, the energy stored from entific literature.1 By comparing the PCE values in the panels kicks in and the day is saved. Perovskites test labs to those documented by literature, Kittner are a new generation of solar panels which have and his team could confirm the accuracy of the PCE garnered much attention for their high efficiency. values and utilize them to construct innovation rate Understanding what drives innovation for solar models called “learning curves.” Dr. Kittner explains technologies is essential to determining techno- that learning curves are graphic models that inlogical improvement in time to halt climate change. vestigate the root causes of a phenomenon – solar Noah Kittner, an assistant professor in UNC-Chapel technology in this case.1 Learning curves illustrate Hill’s Department of Environmental Sciences and the why: what is the impetus behind solar efficiency acclaimed researcher for his work in sustainabil- innovation? Dr. Kittner and his team investigated ity, has recently pub- three factors that affect PCE learning curves - time lished research on the since entering the industry, number of publications innovation of emerg- on that solar technology, and the number of pating solar technolo- ents on the technology.2 gies, where he and his To put their ideas to the test, Dr. Kittner and his team study learning team first needed to confirm the values reported by curves to understand the test labs. His team first scraped a database with if perovskites demon- keywords on the technologies such as “perovskites” Dr. Noah Kittner strate typical innovation or “dye-sensitized” to find the proper articles. They patterns found in solar technology.2 then used text data mining to locate PCE values Dr. Kittner and his team embarked on their re- within literature, searching mainly the abstract secsearch with the intention of comparing Perovskite tions of the literature.2 After compiling a list of the to two other solar technologies: dye-sensitized so- PCE values, Dr. Kittner and his team compared the lar cells and quantum dot solar values reported in sciencells. Dye-sensitized solar cells tific literature to those re“Understanding what and quantum dot solar cells ported by test labs. They drives innovation for solar found that the PCE values are two well-established solar technologies which have long technologies is essential to were nearly identical.2 been the subjects of clean enKittner and his determining whether we can ergy research. Perovskite solar team now had accucells, on the other hand, have improve our technology in rate enough dates and only been in studies since 2009. PCE values to construct time to halt climate change. “ The team analyzed power cona learning curve. They version efficiency (PCE) values, modeled two equations
Figure 1: Uptrend of PCE values in solar photovoltaics as number of research patents filed increases. Image courtesy of Kittner et al. based on the previous hypothesized factors and constructed graphs for each technology. Kittner and his team found some eye-opening information. Perovskitesâ€™s PCE advancement was discovered to be greater than that of dye-sensitized solar. However, the Perovskite advancement was much less than quantum solar dots.1 This could be explained by a number of factors. Although many people believed that perovskites were the fastest growing emerging solar technology, quantum solar dots have been around for quite some time. There are thousands of publications on quantum solar dots which could serve as proof that the cumulative number of publications may correlate to a greater performance improvement for the technology. Kittner also explains that quantum solar dots had a number of patents early on as the technology has applications in LED lighting technology, consumer electronics, and medicine which have caused them to make more PCE growth progress in a shorter period of time than that of perovskites and dye-sensitized technology.1 Although perovskites have received wide attention in their infancy, their learning rate is comparable to dye-sensitized technology. Quantum solar dots had unprecedented innovation that surpassed its competitors. Dr. Kittner and his team can conclude that research from patents to publications on
the technology play a significant role in the learning rate of a solar technology. Kittner says that a combination of continued research as well as government policy is necessary to advance solar technologies. â€œWe need a synergy between both investing in the R&D side and taking the lessons learned from past policy mistakes to create better energy technology and a more livable planet.â€?1 Kittner and his team are optimistic about the future of solar technologies and believe that although they are on a short time limit, if these technologies continue to be researched and developed, they can catch up to the necessary efficiency rates. With continued drive for innovation, society could move closer to abandoning fossil fuels and promotes future wellbeing. Hopefully, the clean energy problem is a learning curve for mankind, one which will be overcome with continued effort.
References 1. Interview with Noah Kittner, Ph. D. 2. Sunter, D.; Ferrall I.; Knapstein, J.; Garfield, D.; Kittner, N.; Kammen, D. IEEE 7th World Conference on Photovoltaic Energy Conversion. 2018, 7, 11471151.
CLOSING THE GAP: USING CONDUCTIVE POLYMERS TO MAKE MORE EFFICIENT SOLAR CELLS HARRIS DAVIS
After well over a century of dependence on coal and oil, energy infrastructure in the modern world is devoted to combustion systems. Now, as we look for ways to supply our energy demand from more sustainable sources, we face economic barriers. Solar power is one of the more popular green systems among scientists, but current processes for refining the semiconductors found in most commercial solar cells are expensive. Consider silicon, which covers the planet’s coasts as sand (silicon dioxide). While the material is abundant, using it to build efficient photovoltaics requires an extremely expensive purification process.2 The question becomes: what if there was a material that offered silicon’s conductive properties, but did not require such A A costly refinement? The short answer is that it already exists—in the form of a group of materials called organic polymers (think plastics). However, engineering polymers that will conduct electricity the same way as semiconductors do requires meticulous chemical design, which researchers at UNC-Chapel Hill are currently developing. The common denominator for all solar cells is that they take advantage of a principle known as the photovoltaic effect. Electrons in a valence band become excited and enter the “conduction band” in which they can flow freely; the energy which allows the electron to become excited comes from the absorption of sunlight in the form of a photon.9 This excitation lets electrons move freely and produce a cur-
rent. The energy required to excite an electron from the valence shell to the conduction band is known as the “band gap,” and this requirement determines the colors—or wavelengths of light—a photovoltaic material can absorb. To even consider conduction and band gaps in organic polymers, the compounds must be conjugated—a property which can be synthetically designed by a chemist. A conjugated material has delocalized electrons, similar to those which exist naturally in metals. Scientists engineering organic polymer-based photovoltaics (OPVs) spend much of their time experimenting with energy levels and designing ideal band gaps, as this principle is critical in generating voltage. Generally speaking, deeper band gaps, which involve low-energy valence shells, are associated with higher voltages in photovoltaic materials. More electronegative materials—such as fluorine—offer a way to achieve those deeper band gaps, and thus greater solar cell efficiency. Since 2006, Dr. Wei You and his group of researchers in UNC’s chemistry department have been working to enhance the photovoltaic effect in OPVs. A highlight of their work has been the development of a methodology to add fluorine— the most electronegative element—to polymers to deepen their band gaps. In 2009, the You group had the idea to replace specific hydrogen atoms in conjugated organic polymers with fluorine, as this element is not much larger than hydrogen and can
PRIOR TO THE 1980S, EVERYBODY THOUGHT THAT PLASTICS WERE INSULATORS. BUT WITH HEEGER’S, SHIRAKAWA’S, MACDIARMID’S RESULTS, WE ARE NOW SEEING THAT PLASTICS ACTUALLY CAN CONDUCT ELECTRICITY.
Carolina Scientific largely maintain other structural features of the molecule. Since then, they have been working to make fluorination viable as a means of band gap deepening. In early 2011, Dr. You’s team achieved the “first successful application of fluorine to a donor– acceptor conjugated polymer.”4,5 While 7% efficiency does not sound like much when compared to some semiconductor-based solar cells,6 this was a record for OPVs at the time, and the team’s work was praised by groups such as Thomson Reuters upon publication.2
Left: Dr. Wei You; Right: Jeromy Rech
Flash forward ten years, and the You Group has honed the fluorination process extensively. They recently experimented with a dual fluorinated linker unit (dFT)7—which is a chemical that is used to join monomers into polymers—to test its efficiency against similar non-fluorinated conjugated polymers. Using a polymer lacking functional groups as a model (HTAZ), members of the You Group led by Jeromy Rech found that, with dual fluorinated linkers (dFT-HTAZ), the polymer operated at a much higher efficiency than its non-fluorinated counterpart.7 After synthesizing HTAZ and dFT-HTAZ, the You group examined the chemical properties of both for comparison. While the polymers had band gaps of similar energy (which allowed them to absorb similar wavelengths of light to generate an electric current), lower orbital occupation was found for dFT-HTAZ (i.e., the band gap was deeper within the molecule). This contributed to the key photovoltaic property
of interest for dFT-HTAZ: a higher open-circuit voltage and, as a result, greater efficiency. Further experimentation found that blending dFT-HTAZ with the ITIC-Th1 fluorinated electron acceptor brought efficiency to nearly 10%, which constituted a nearly 300% improvement from the non-fluorinated HTAZ polymer.7 The success of this process has broad implications for the field of OPVs. Making use of fluorine’s high electronegativity to deepen the energy levels of these polymers has a massive ability to make these materials more efficient. Although the idea of building OPVs has been around since the 1980s, pioneered by researchers such as Alan Heeger and Richard Friend,1 it was only after the principle of band gap engineering was introduced to the field that the use of these polymers became viable. We now know OPVs can be extremely efficient: the record efficiency achieved by Dr. You and his colleagues was over 13.5%,8 and the most efficient organic polymer solar cell to date was built in January 2020, with an efficiency over 18%.9 However, barriers to OPVs still exist in the mainstream. The next logical step to bring down the cost of solar power is to find a way for these materials to compete with semiconductors such as silicon in the energy market, and conjugated polymers face a severe disadvantage in terms of stability. While 3–-5 years of use has been demonstrated for some OPVs, silicon cells can last for 30. But researchers, including those at the You Group, are working to close this gap, and as they make progress they are earning national attention for the potential of their work. The affordability—as well as the physical flexibility— of OPVs has caught the eye from the United States military as potential lightweight power sources to replace the heavy batteries currently in use overseas. It is difficult to predict the length of time between now and widespread implementation of OPVs. According to Dr. You, however, the outlook on this new frontier is promising. The specific nature of the You Group’s work, which achieves higher efficiency by fluorinating a polymer linker (as opposed to the entire molecule), offers experimental freedom to researchers looking to build off of these results. This freedom is also attractive to researchers who are exploring new polymerization methods. With a growing interest in inexpensive OPVs within the scientific community, we can expect to see shifts towards economic soundness on the front of sustainable energy.
More information about conjugated polymer photovoltaics is available at the You Group’s website: https://www.weiyougroup.org/. Figure 1: Models of non-fluorinated vs. difluorinated polymers Image courtesy of reference 6 (refer to publication).
References (cont. from pg 23)
1. Interview with Wei You, Ph.D. 2/5/2020 2. Email with Wei You, Ph.D. 2/19/2020 3. Gokul Dharan, Jordan Hanania, Kailyn Stenhouse, Jason Donev. Energy Education - Conduction band. https://energyeducation.ca/encyclopedia/Conduction_band (accessed February 17th, 2020). 4. Zhou H, Yang L, Stuart AC, Price SC, Liu S, You W. Development of Fluorinated Benzothiadiazole as a Structural Unit for a Polymer Solar Cell of 7 % Efficiency. Angewandte Chemie International Ed. 2011, 50(13), 2995–2998. doi:10.1002/anie.201005451 5. Price SC, Stuart AC, Yang L, Zhou H, You W. Fluorine Substituted Conjugated Polymer of Medium Band Gap Yields 7% Efficiency in Polymer−Fullerene Solar Cells, Journal of the American Chemical Society 2011, 133(12), 4625-4631. doi:10.1021/ja1112595 6. Green MA. High efficiency silicon solar cells. In Seventh EC Photovoltaic Solar Energy Conference; Adolf Goetzberger, Willeke Palz, G. Willeke, Eds; Springer: Dordrecht, 1987; pp 681-687. 7. Rech J, Yan L, Peng Z, Dai S, Zhan X, Ade H, You W. Utilizing Difluorinated Thiophene Units to Improve the Performance of Polymer Solar Cells. Macromolecules 2019, 52(17), 6523-6532. doi:10.1021/acs. macromol.9b01168 8. He D, Zhao F, Xin J, Rech J, Wei Z, Ma W, You W, Li B, Jiang L, Li Y, Wang C. A Fused Ring Electron Acceptor with Decacyclic Core Enables over 13.5% Efficiency for Organic Solar Cells. Advanced Energy Materials. 2018, 8(30), 1802050. doi:10.1002/aenm.201802050 9. Liu Q, Jiang Y, Jin K, Qin J, Xu J, Li W, Xiong J, Liu J, Xiao Z, Sun K, et al. 18% Efficiency organic solar cells. Science Bulletin 2020. doi:10.1016/j.scib.2020.01.001.
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PROTECTING STEM CELLS AND SETTING THEM FREE Megan Butler
Fluorescent image of the distal tip cell in the gonad of C. elegans. Image courtesy of Kacy Gordon.
life sciences Dr. Kacy Gordon distinctly remembers taking developmental biology as an undergraduate at Dartmouth College and looking at images from microscopes for the first time. “It just felt like we Dr. Kacy Gordon were seeing the secrets 1 of the universe.” She pursued those secrets, obtaining a Ph.D. from the University of Chicago and then working as a postdoctoral researcher at the other blue school down the road. It was Dr. Gordon’s time at Duke that led her to study the roundworm Caenorhabditis elegans and its germ stem cell niche – a cellular system that protects and maintains the population of germ cells. She and her colleagues identified many genes that are involved in the regulation of germ stem cells in the C. elegans niche. In the summer of 2019, Dr. Gordon arrived at UNC-Chapel Hill to set up her own lab, and the germ stem cell niche that had infatuated her so much it became one of her main research focuses. C. elegans are very small organisms. Their bodies are made up of only 905 cells, yet their sexual organs arms can each carry 1000 germ stem cells at any given time. One single hermaphrodite, a worm that can self-fertilize, can have 300 to 350 babies or up to 1000 babies if fertilized by a male.1 For such small creatures to have so many
ability to replicate themselves – they are either used up to produce baby worms, or die off. Thus, the distal tip cell uses a set of extended protrusions to enwrap germ stem cells to regulate their differentiation and keep them replicating through mitosis.2, 3 In her recent paper entitled “Ectopic Germ Cells Can Induce Niche-like Enwrapment by Neighboring Body Wall Muscle,” Dr. Gordon and her colleagues investigated whether or not germ cells can embed into tissues other than the gonad and potentially create a stem cell niche, called an ectopic niche, in those tissues.4 This research could help to clarify the existence of ectopic niches in C. elegans as well as the mechanism of the gonad germ cell niche. For humans, this research could further elucidate how tumors metastasize in cancers and how stem cells are maintained and released for regenerating and engineering tissues. Dr. Gordon and her colleagues discovered that germ stem cells in C. elegans can induce a niche-like environment when in contact with a distinct tissue – in this case, muscle cells.4 Like the distal tip cell, the cells of the body wall muscle enwrapped the germ stem cells, indicating that stem cells can create niches outside of their endogenous niche. The researchers used genetic techniques to knock down genes, disrupt the gonad membrane, and then release some germ cells into the body cavity. Then, they used live imaging of the worms through a microscope to see whether the germ cells would fuse with or actively
The endeavor of science is really fun, but it’s a story that takes a long time to write. offspring, they need to maintain a large germ stem cell population to be differentiated into gametes when necessary, which means there must be some regulation of the stem cells to keep certain portions regenerating differentiating others, in a controlled or sporadic manner. The system of protecting and maintaining stem cells is called a stem cell niche. The C. elegans germ stem cell niche has been studied for over 40 years. As the first niche to be studied in-depth, it has yielded a great deal of information regarding stem cell biology. In worms, the niche cell is called the distal tip cell. If the distal tip cell is terminated, all of the worm’s germ cells differentiate and no longer have the
invade the muscle cells when they came in contact. As it turned out, neither of those events occurred. The muscle cells actually extended protrusions, enwrapping the escaped germ cells. However, this niche-like environment was found to be unable to support the proliferation of the germ stem cell population, as this was deemed reliant on the distal tip cell signals.4 While the specificities of the germ stem cell niche in small worms may seem unrelated to human health and disease, Dr. Gordon’s research has large implications for stem cell biology. “Sometimes a weird little lab critter like a fluorescent worm gonad or a genetically modified
fly lets us push the boundaries of what we can see about biology and development of all of these living creatures.”1 In pushing those boundaries, these particular results suggest that even when placed in unnatural environments, stem cells can induce the tissues around them to form nichelike environments. A similar interaction is likely important for metastasizing tumors in human tissues, and such results could be used clinically for tissue engineering and regeneration if niche-like environments can be created even without a gonad. Dr. Gordon hopes to grapple more with a different question of how germ stem cells in their endogenous gonad niche interact with the somatic cells around them. It has long been thought that the distal tip cell would sit in the gonad of the worm and stem cells would sporadically detach from the niche, and then another somatic cell called the sheath would cover the newly differentiating germ cells. Interestingly, this model is very different from other known stem cell niches, such as that of Drosophila melanogaster, the fruit fly. In flies, the germ cells are released from the niche in a controlled way. Recent research indicates that the sheath cell in worms that enwraps differentiating germ cells seems to reach farther towards the distal tip cell than initially anticipated. As such, Dr. Gordon wants to probe for a potential interaction between these somatic cells and re-visit the question of the mechanism of the C. elegans germ stem cell niche. Considering whether C. elegans could be hiding the same old control and release story, she hopes that a better understanding of the structure of this specific niche will reveal more about general requirements for stem cell systems. There is still a lot of work to be done; as Dr. Gordon says, “The endeavor of science is really fun, but it is a story that takes a long time to write.”1 Dr. Gordon is just getting started. Figure 1: Shows the enwrapment of ectopic germ stem cells by muscle tissue in the body wall when the gonad is ruptured to release the germ stem cells. Image courtesy of Kacy Gordon.
1. Interview with Kacy L. Gordon, Ph.D., 1/21/20. 2. Byrd, D. T.; Knobel, K.; Affeldt, K.; Crittenden, S. L.; Kimble, J. A DTC Niche Plexus Surrounds the Germline Stem Cell Pool in Caenorhabditis elegans. PLoS ONE 2014, 9, e88372. 3. Linden, L. M.; Gordon, K. L.; Pani, A. M.; Payne, S. G.; Garde, A.; Burkholder, D.; Chi, Q.; Goldstein, B.; Sherwood, D. Identification of regulators of germ stem cell enwrapment by its niche in C. elegans. Developmental Biology 2017, 429, 271-284. 4. Gordon, K. L.; Payne S. G.; Linden-High, L. M.; Pani, A. M.; Goldstein, B.; Hubbard, E. J. A.; Sherwood, D. R. Ectopic Germ Cells Can Induce Niche-like Enwrapment by Neighboring Body Wall Muscle. Current Biology 2019, 29, 823-833.
A zebrafish specimen. Image courtesy of Wikimedia.
Neuroimmunology: A Dialogue Between Two Crucial Systems Andrew Prevatte The human body constantly collects information about its environment, sending signals, and commanding actions through an intricate network known as the nervous system. A flaw or short-circuit in the nervous system could mean catastrophe for the rest of the body. The vital importance of such a widespread system is what piqued Dr. Celia Shiau’s interest, which led her to study another crucial body system and eventually, one of the most versatile and extensive cell types in the body. Dr. Shiau works within the dynamic field of neuroimmunology, a subfield of molecular Dr. Celia Shiau biology which examines the interaction between the nervous system and immune system, the body’s defense against infection. These two networks are often intertwined; when the nervous system is disrupted by disease, the immune system usually responds in defense. Knowing how these two systems interact can lead to a better understanding of how homeostasis, or bodily equilibrium, is maintained across the body. One particular component of the immune system is of interest to Dr. Shiau: macrophages. Macrophages, which are big “cell eaters” that help clean up cellular debris across the body, are involved in signaling and have been implicated as impacting the connections between neurons. Dr. Shiau’s states, macrophages are a “very unique and phenomenal cell type that is versatile and dynamic.”1 Fully understanding the inner workings of macrophages would allow for major developments in immunotherapy, with widespread applications, including cancer remission. Macrophages reside in every tissue across the body, performing a myriad of different functions. In fact, they can change morphology and behavior in
response to a small change in their microenvironment. The unique sensitivity makes macrophages well-equipped for their environment in the brain, the hub of the nervous system. Macrophages that reside in the brain are known as “microglia.” Dr. Shiau specifically examines microglia, due to their unique nature of being the only type of immune cell residing in the brain.1 Much is still unknown about microglia, but Dr. Shiau’s lab is determined to develop a better picture. What are the molecular controls that regulate activity of microglia? What genes are involved in the development of microglia, or the lack of them? What does a loss of microglia look like — are there structural changes in the brain, or consequential impacts on animal behavior? These are the questions about microglia which currently interest Dr. Shiau.
Figre 1, left: Macrophage of a mouse phagocytosing Figure 2, right: Microglia (green) and neurons. Images courtesy of Wikimedia.
In order to observe and test macrophages, Dr. Shiau uses an interesting organism, the zebrafish. Zebrafish processes bear remarkable similarities to human processes, as their tissues, organs, and cell types are highly conserved from fish to human. However, it is not only the applicability of results that drew Dr. Shiau to study this model organism. Zebrafish also have high optical transparency, meaning that the inner workings of their tissues
fect of no macrophages on the gut microbiota. The gut encompasses the largest part of the nervous system, other than the brain and the spinal cord. A disruption in its population of microbes could be disastrous. While there is robust research on environmental factors affecting gut microbiota, not much is known about contribution from the host. Using zebrafish, Dr. Shiau mutated irf8, which caused no macrophages to form in the gut. As such, the gut microbiota was disrupted, and the immune system as a whole was dysregulated.6 The research not only elucidated interesting connections between the immune system and colonization of normal gut microbes, but it also has implications for a greater understanding of the brain-gut axis. Dr. Shiau’s work is at the forefront of understanding macrophages, a unique and extensive cell type. A full picture of macrophages mechanisms Figure 3: Comparison of gut microbiota with and without will contribute to leaps in development of immunomacrophages/ Image courtesy of Dr. Celia Shiua. therapy. Macrophages recognize and phagocytose, or eat, specific cells. If their fundamental engineerand cells are easily observed in real time. Dr. Shiau ing is understood, then we could develop treatbelieves that observing cells in vivo, or live cells in ments to remove unhealthy or cancerous cells from their natural environments, is crucial to wholly un- a patient’s body.1 Dr. Shiau leads the charge in this derstanding a process.1 Dr. Shiau developed a novel unprecedented and promising field of study. process for time-lapse imaging during her PhD, using slices of chicken embryo brains to observe the References early stages of nervous system development.2 She 1. Interview with Celia Shiau, Ph.D. 2/5/20. brought this same level of meticulous detail to the 2. Shiau CE, Das RM, Storey KG. An effective assay for observation of macrophages in zebrafish. high cellular resolution time-lapse imaging of sensory Dr. Shiau has already identified multiple genes placode formation and morphogenesis. BMC Neurosci. vital to macrophages, using a method known as 2011, 12:37. Published 2011 May 9. doi:10.1186/1471“forward genetics.” The process of forward genet- 2202-12-37 ics involves making many random mutations across 3. Shiau CE, Monk KR, Joo W, Talbot WS. An antia genome, and then selectively isolating specific inflammatory NOD-like receptor is required for ones. Making a mutation in a gene effectively weak- microglia development. Cell Rep. 2013, ;5(5):1342–1352. ens or silences its expression, allowing the research- doi:10.1016/j.celrep.2013.11.004 4. Meireles AM, Shiau CE, Guenther CA, Sidik H, er to observe the effect (or lack thereof ) of a specific Kingsley DM, Talbot WS. The phosphate exporter gene.1 With this method, Dr. Shiau has characterxpr1b is required for differentiation of tissue-resident ized three separate genes acting upon microglia so macrophages. Cell Rep. 2014, ;8(6):1659–1667. far: nlrc3-like, xpr1b, and irf8.3, 4, 5 When these genes doi:10.1016/j.celrep.2014.08.018 are inactivated, effects range from broad impacts 5. Shiau CE, Kaufman Z, Meireles AM, Talbot WS. on the entire macrophage population to the lack Differential requirement for irf8 in formation of of microglia formation. For example, irf8 acts upon embryonic and adult macrophages in zebrafish. PLoS the DNA itself to induce precursor cells to become One. 2015, ;10(1):e0117513. Published 2015 Jan 23. macrophages; without irf8, the presence of macro- doi:10.1371/journal.pone.0117513 6. Earley AM, Graves CL, Shiau CE. Critical Role for phages in general is in jeopardy.5 In this same vein, Dr. Shiau has also examined a Subset of Intestinal Macrophages in Shaping Gut the impact of a lack of macrophages in organs. In Microbiota in Adult Zebrafish. Cell Rep. 2018, ;25(2):424– her most recent study, Dr. Shiau observed the ef- 436. doi:10.1016/j.celrep.2018.09.025
T h e M a g n e tic M a p in S e a Sam Shutt
Dr. Catherine Lohmann, an animal behavior biologist at UNC-Chapel Hill, is fascinated with how sea turtles find their way home. Sea turtles travel hundreds, and even thousands of miles across the ocean. Yet they somehow manage to return to the precise location where they hatched. This could be attributed to sea turtles’ special sense known as the magnetic map.1 Sea turtles appear to utilize the Earth’s magnetic field to recognize specific geography. Indeed, the turtles can distinguish between different coastlines and find the exact area where they were born. Dr. Lohmann and her lab uncovered evidence that supports the theory that sea turtles geomagnetically imprint on the magnetic field of where they were born.2 Imprinting may allow sea turtles to recognize the magnetic field of their home. Dr. Lohmann’s research has contributed to scientific knowledge of long-distance marine animal migration and will have tangible applications in the near future. Dr. Lohmann began researching sea turtles in 1989. Over the years, she and her husband, Kenneth Lohmann, have created a lab that is at the forefront
of sea turtle and marine animal navigation research. Much of their collaboration occurs in Florida, where they study how loggerhead sea turtles Dr. Catherine Lohmann detect magnetic fields. In one important experiment, they collected young turtles along the coast and attached harnesses to them with computerized tracking systemts.3 They applied different magnetic fields to the newly hatched turtles in an outdoor water arena by using a surrounding metal coil. Then, they recorded turtle movement orientation using the tracking system. Dr. Lohmann found that turtles exposed to northern magnetic fields oriented themselves south and those exposed to southern magnetic fields oriented themselves north. The experiment clearly showed that sea turtle navigation is affected by the Earth’s magnetic field and that turtles seemed to use some kind of magnetic map (Figure 1). Sea turtles appear to use the map by responding to both the inclination angle
and intensity of the Earth’s magnetic field. The intensity of the Earth’s magnetic field is strongest at the poles. Inclination field lines, however, are somewhat more difficult to understand. The lines crisscross and are affected by the intensity of the Earth’s magnetic field, marking different geographic locations with distinct magnetic fields for sea turtles to recognize and remember.
Figure 1: Dr. Lohmann’s Detection System. Source courtesy of Lohmann et al.
After Dr. Lohmann and her lab acquired evidence for a magnetic map in sea turtles, they became interested in exploring the relationship between the genes of sea turtles and the Earth’s magnetic field. The Lohmann lab studied sea turtles along the coast of Florida and examined their genetic makeup. They found that turtles living at similar latitudes were genetically similar;4 even turtles at the same latitude but separated from each other by large distances bore genetic resemblance. In contrast, sea turtles that were near each other but at different latitudes were not as genetically similar. The evidence strongly suggests that there is an interaction between magnetic fields and the genes of sea turtles. Perhaps, turtles that are genetically similar live at similar latitudes because of the magnetic fields or perhaps the magnetic fields have affected their genes somehow. There is no definitive answer of how sea turtle genes are affected by the Earth’s magnetic field yet, but the Lohmann lab’s research provides a promising start for future research on this topic. When asked to explain the reason behind her primary focus on sea turtles for so many years, Dr. Lohmann simply responded, “I was captivated.”5 Sea
turtles are special animals that perform fascinating feats. Sadly, almost all species of seas turtles are classified as endangered, but Dr. Lohmann’s research may one day help in the conservation of sea turtles. Turtles may be made to geomagnetically imprint on specific magnetic fields so that they may return to safe locations later in life instead of populated and polluted coastlines. Nonetheless, there may be unforeseen consequences if sea turtles imprint on different magnetic fields. There are many avenues for research which the Lohmann Lab plans to pursue in the future. The physiological processes of sea turtle magnetic detection and navigation remains a mystery. Dr. Lohmann plans to do neurobiological work on fish that also detect magnetic fields, in an effort to further explain the magnetic map. Furthermore, she hopes to learn whether or not marine animal navigation, influenced by magnetic detection, is a widespread phenomenon. Dr. Lohmann is optimistic about the future for marine animal navigation research and where it could lead: “I feel we are learning something that can be very applied and can expand our understanding.”5 Dr. Lohmann’s research has radically expanded scientific knowledge on sea turtle navigation and the magnetic map. Her important work will continue to do so, and one day the mysterious process of how sea turtles return home may be fully understood.
1. Lohmann, K. J.; Lohmann, C. M. F. There and back again: Natal homing by magnetic navigation in sea turtles and salmon. J Exp Biol. 2019, 222, 184077-184087. 2. Lohmann, K. J.; Putman, N. F.; Lohmann, C. M. F. Geomagnetic imprinting: A unifying hypothesis of longdistance natal homing in salmon and sea turtles. 2008, 105, 19096-19101. 3. Lohmann, K. J.; Lohmann, C. M. F.; Ehrhart, L. M.; Bagley, D. A.; Swing, T. Geomagnetic map used in sea-turtle navigation. Nature. 2004, 428, 909-910.. doi:10.1038/428909a 4. Lohmann, K. J.; Lohmann, C. M.; Brothers, J. R.; Putman, N. F. Natal Homing and Imprinting in Sea Turtles. Biology of Sea Turtles 2013, 3, 59-77. 5. Interview with Catherine Lohmann, Ph.D. 02/07/2020
Exosomes as Drug Delivery Vehicles for Parkinson’s Disease Therapy Diane Youngstrom Exosomes are the epitome of “small but mighty.” They have the potential to revolutionize drug delivery by allowing impermeable compounds to cross the blood brain barrier (BBB). Exosomes are effective Dr. Elena Batrakova drug carriers because they are exceedingly small – nanosized, in fact (see Figure 1) – and because they have multiple adhesive proteins on their surface that facilitate their specialization in cell-to-cell communication by binding to their targets. In addition, exosomes have plenty of interior space to house compounds of interest.1 Dr. Batrakova – a research associate professor at the Eshelman School of Pharmacy – and her collaborators have used exosome-based drug formulations to treat cancer, HIV, infectious diseases, inflammatory disorders, and neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. According to Dr. Batrakova, crossing the BBB is one of the foremost obstacles in drug delivery because “the brain is like a sanctuary.”2 Pathogens in the bloodstream are thwarted by the BBB due to its high selectivity for what it allows to pass into the brain. While the selective nature of the BBB protects a healthy brain, it also prevents drugs from helping a sick brain. Thus, developing innovative mechanisms to cross the BBB is crucial for the advancement of treatments for neurodegenerative diseases and other pathologies. Exosomes are an exciting frontier in drug delivery. Similar to how Uber Eats uses an address to deliver food to a customer, exosomes provide a biological address to deliver drugs to specific locations in the brain and body. Exosomes have a natural lipid bilayer with many adhesive proteins on their surface, which facilitate the binding of exosomes to their target cells, as well as a roomy interior that can be packed with drug therapies to be carried across the BBB.3 Exosome treatments are based on the natural communication mechanisms of our body used to deliver proteins or genes to
Figure 1: Exosome size compared to the average cell, bacteria, and virus. Figure courtesy of Nina Koliha
other cells and organs. Batrakova’s lab decided to “use macrophages as smart vehicles because if you load them with nanoparticles they know where to go”.2 Macrophages are a type of white blood cell that devour foreign materials to protect the body, and are instrumental to natural immune responses. Equipping macrophages with exosomes harnesses the body’s immune system and bolsters the body’s ability to fight diseases. The exosomes from macrophages travel to sites of inflammation, unzipping the tight barriers of the BBB (see Figure 2). Because exosomes are naturally produced by many cells in the body, they are better than previous methods at interacting with target cells for more selective drug delivery. The unique proteins and lipids on the surface membrane of exosomes allow them to communicate with neighboring cells and cells in distant systems. In addition, exosomes are less likely to be filtered out by the liver and spleen because immune cells – such as macrophages – recognize them as non-pathogenic, which leads to decreased exosome degradation. Therefore, more of the drug injected via exosomes will be available for combating disease. In general, increasing bioavailability inherently lowers the cost of treatment, and reduces the risk of side effects, because less of the compound is required. After researchers determined the superiority of
Carolina Scientific exosomes over many polymer-based formulations, the next step was to ascertain the best method for administration. When thinking of drugs, the first thought that pops up is typically pills. However, oral delivery is surprisingly inefficient. 2-3% of drugs taken orally are able to survive the acidity of the stomach and the filtration of the liver to even make it into the bloodstream, let alone into the brain.2 Intranasal delivery and intravenous administration are far superior to oral administration because more of the drug can be absorbed into the blood and brain, which is why Dr. Batrakova uses intranasal injections in many of her ongoing projects. Investigating alternative injection mechanisms is an overarching goal of the lab. Dr. Batrakova and her lab are developing exosome treatments for Parkinson’s disease along with many other diseases. Dopamine is important for reward, motivation, and movement. Damage to dopamine neurons due to inflammatory responses and oxidative stress causes the symptoms of Parkinson’s disease (see Figure 3).4 There are no current treatments that have successfully stopped or reversed the progression of Parkinson’s disease, in part because promising therapies have not been able to cross the BBB. Dr. Batrakova began her investigation by delivering catalase to in vivo mouse models via exoCAT, the exosomal-based formulation of catalase. Catalase is a powerful antioxidant that can protect the endangered dopamine neurons, but it has to get past the BBB. Once the exosomes are filled with drugs, they are re-injected into the mouse. A similar method would be used in clinical trials: white blood cells would be isolated from a patient’s blood, exosomes secreted from macrophages would be extracted and loaded with the therapeutic drug, and the loaded exosomes would be re-administered back into the patient (see Figure 2). Dr. Batrakova is eager to replicate her success with exosomes in another animal model as a step closer to clinical trials. Imagine being able to treat diseases ranging from cancer to Parkinson’s to HIV with a drug-filled particle one million times smaller than a grain of sand. Dr. Batrakova’s research aims to contribute to the discovery and development of exosome-based treatments for Parkinson’s disease, Alzheimer’s disease, breast cancer, and many other diseases. The solution to these conditions is inevitably complex, but exosomes are a valuable piece of the larger puzzle.
Figure 2: The flow of exosome production and readministration. Figure courtesy of Dr. Batrakova et al.
Figure 3: Inflammation and oxidative stress of dopamine in Parkinson’s disease. References 1. Batrakova, E. V.; Soo Kim, M. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 2015, 219, 396-405. 2. Interview with Elena Batrakova, Ph.D. 09/17/2019. 3. Soo Kim, M. S.; Haney, M.; Zhao, Y.; Yuan, D.; Deygen, I.; Klyachko, N. L.; Kabanov, A. V.; Batrakova, E. V. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomedicine 2018, 14, 195-204. 4. Haney, M. J.;, Klyachko, N. L.;, Zhao, Y.;, Gupta, R.;, Plotnikova, E. G.;, He, Z.; Patel, T.; Piroyan, A.; Sokolsky, M.; Kabanov, A. V.; et al., Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015, 207, 18-30.
Synthesis of Organic Products Inspired From Natural Compounds Sneha Makhijani
Medical illnesses and diseases are rampant across the world. With new strains of diseases like the influenza, the coronavirus and existing maladies like HIV/AIDS and others, pharmaceutical companies and research labs are striving towards working towards finding medicines and other cures. Compounds or medicines that may exert a direct physiological effect on animals, plants, or microorganisms are called Biologically Active Compounds (BACs). Compounds like vitamins, antibiotics, and insecticides are all BACs as they have direct physiological effects on living beings. BACs have a great importance in the healthcare and pharmaceutical industries as they have a diverse range of effects in the human body and can be used to regulate biological processes for instance, antioxidant properties of some BACs. BACs are complex structures created from organic molecules, which are generally any chemical compounds that contain carbon.1 Organic chemistry is the study of the properties, synthesis, reactions of these organic compounds. Dr. Sidney Wilkerson-Hill, Assistant Professor in the Department of Chemistry at the University of North Carolina at Chapel Hill, is leading the synthesis of these Biologically Active Compounds as they aid in the synthesis of natural products to be used in medicines. As a pioneering researcher in organic chemistry, Dr. Hill’s lab foDr. Sidney Wilkerson-Hill cuses on three main processes. The first is the development of new chemical reactions and their reaction methodology.1 These are critical for advances in different sectors like pharmaceutical, biological, and material. The main idea behind these reactions is access to chemical space.1 This is a concept which refers to the property of space that belongs to molecules which are defined by principles of boundary conditions in a chemical compound. Cycloaddition reactions are especially important because they allow a rapid increase in this chemical space due to their complexity.1 Cycloaddition reactions are specific chemical reactions used in organic chemistry which basically
Figure 1: Glycosmis stenocarpaand Murraya koenigii. Two different shrubs found throughout Asia from which dimers are obtained. Image Courtesy of Dr. Sidney Wilkerson-Hill.
have a cyclic or circular structure to them. The Hill Lab focuses on developing cycloaddition reactions which have such a relative spatial arrangement of atoms. Natural Products which have been isolated from natural sources like bacteria, plants, and marine sponges often have important biological function. For instance, the Biologically Active Compounds can be used in anti-HIV or anticancer drugs.1 These compounds are thus very useful for developing new drugs and pharmaceuticals. These compounds can also be used to understand biologically retroactively by studying the effects of the molecular drugs and their reactivity in the complex chemical environments.1 That’s why the use of natural products to understand complex biology is a major aspect of Dr. Hill’s Lab. Complex natural products can be obtained by the synthesis of a sequence of reactions and this is the third main goal of the Hill Lab.1 Strategies to make these synthetic products can help fuel innovative reaction processes. This can help uncover the new reactivity of small molecules which can also help replace the use of natural products which may be lesser in quantities that are used for particular drugs.1 The total synthesis of this product also refers to how the structure of these products can be deciphered in order to understand how they function. The Hill Lab uses these organic compounds and cycloaddition reactions to understand how these natural products’ functions relate to their structure.1 Dr. Hill’s passion for chemistry originated in a
high school Science Olympiad he was compelled Dihydroindoles.2 Dr. Hill’s Lab is working on making to be a part of. From there he went on to study at Biologically Active Compounds that contain differNC State and majored in chemistry and textiles and ent organic functional groups which can possibly then went to graduate school at UC Berkeley. After be used to synthesize different drugs. completing his postdoctoral studies at Emory UniThrough his recent research paper, Dr. Hill’s versity, he joined UNC-Chapel Hill. One of the main main focus was observing how certain structures aspects of Dr. Hill’s research is using new reactions relate to the speeds of certain catalyst reactions.1 to create dimeric compounds.2 Dimers are com- This study focused on trying to understand the kipounds that consist of two identical monomeric netics, which is measuring and studying the rate of molecules. Using a sequence of events, for instance a chemical reaction, of a cyclic compound and using like two separate pathways, a product can be this data to try and develop conditions for how the formed by completing two steps at once.2 Dimers reaction can proceed even with a smaller amount of have unique dimerization patterns and other char- the catalyst being used in the reaction.3 A catalyst is acteristic features. Dimers also have unique stereo- a substance that enhances the rate of a chemical rechemistry, or chemical action without itself unorientations and spatial dergoing any change arrangements. They chemically. This paper have various sources helped understand the but some of them are kinetics of the reaction obtained from small based on a variety of shrubs like Glycosmis catalysts.3 This informastenocarpa and Murtion can further help raya koenigii which are us understand how found throughout Asia fast a product can be (Figure 1). Symmetric obtained based on the dimers can also undervariety of catalysts that go a process known as are used. In his study, desymmetrization to Dr. Hill used Dirhodium form a nonsymmetric Figure 2: Depiction of various Dirhodium catalyst structures. catalysts due to their dimer. versatile catalyst naImage Courtesy of Dr. Sidney Wilkerson-Hill. One of the most inture, including transforteresting compounds Dr. Hill worked on during his mations that involved cyclic compounds (Figure 2).3 Postdoctoral studies were called Dihydroindoles.2 Dr. Hill aims to use all this to develop the basis Indoles are important motifs found in Chemistry. of his research at UNC-Chapel Hill. He wants to creIn nature, they are found in amino acids, the com- ate these synthetic molecules using natural prodpounds that make up proteins. For instance, it is the ucts by understanding the underlying chemistry amino acid, Tryptophan that is present in turkey that behind it.1 With his expertise in the organic chemmakes you sleepy after a Thanksgiving meal!1 Using istry field and his passion for fostering curiosity and these Dihydroindoles, biological reactions can be an appreciation for science, Dr. Hill continues to lead ground-breaking research and exert a positive used to incorporate them into synthetic products. One of the key methods used in this research force in his research. paper was the NMR, or the Nuclear Magnetic Resonance.2 This is a common method used to assess References the structure of a compound. By configuring the 1. Interview with Dr. Sidney Wilkerson-Hill, March 11, structure, it can be understood how this compound 2020. carries out its reactions. The NMR is basically an MRI 2. Wilkerson-Hill, S. M.; Haines, B. E.; Musaev, D. G.; for chemical compounds. Different organic groups Davies, H. M. L. “Synthesis of [3a,7a]-Dihydroindoles called functional groups have different signature by a Tandem Arene Cyclopropanation/[3,5]-Sigmatropic data. This paper focused on the synthesis of these Rearrangement Reaction” 3. Wei, B.; Sharland, J. C.; Lin, P.; Wilkerson-Hill, S. M.; Dihydraindoles using specific synthesis mecha- Fullilove, F. A.; McKinnon, S.; Blackmond, D. G.; Davies, nisms and their structures.2 H. M. L. “In Situ Kinetic Studies of Rh(II)-Catalyzed Using this research Dr. Hill is continuing his Asymmetric Cyclopropanation with Low Catalyst research using this knowledge to make structures Loadings” based on the knowledge of the synthesis of these
What Causes Disease? Using Computational Biology to Understand Disease Mechanism Rajee Ganesan
In a time of groundbreaking technological advancement, it is no surprise that computation methodologies have found their way into fields such as medicine and biology. This is exactly what Dr. Di Wu hopes to explore in her research within both the Adams School of Dentistry and the Gillings School of Global Public Health Department of Biostatistics. Dr. Wu has pursued research across the globe, completing a B.S. at Shanghai University, M.S. in Biostatistics at Case Western University, and Ph.D. in Statistical Bioinformatics at the University of Melbourne in Australia. 1 She Dr. Di Wu began her education in the wet laboratory studying biotechnology, but then slowly moved into a data analysis when she found her passion for getting to see the data first and being able to analyze and interpret the results. 1 Wu is very adamant that having a background in the wet lab has allowed her to better understand research questions that she is developing computational solutions for, and she is currently considering starting a wet lab to validate her computational findings. Before leading her own research, Dr. Wu spent
her Ph.D. studying gene expression patterns in breast cancer subtypes, and developed gene set testing methodologies to summarize gene patterns between stem cell data and data from patients of different breast cancer subtypes. 1 Her work was focused on trying to prove the hypothesis that different subtypes in cancer patients could be attributed to a difference in cell types.1 She further developed her work during a postdoctoral career at Harvard Medical School and their Statistics Department, running meta-analysis to correlate risk genes and to study protein-protein interactions with neighboring genes.1 Dr. Wuâ€™s laboratory at UNC-Chapel Hill focuses on three areas: cancer genomics, microbiome sequencing, and single-cell RNA sequencing.1 Dr. Wu stresses that she is able to utilize the skills acquired from her previous work and apply it to current projects. With the wide range of collaborators available at UNC, she was able to broaden her horizons and work on cutting-edge projects. Her project to use data integration tools in her current research to identify relationships between genomic components and the microbiome , and to further understand how diseases progress. One of her current projects studies tools such as functional SNP-sequencing (SNP-seq)
Carolina Scientific and Flanking Restriction Enhanced Pulldown (FREP). SNPs, or single nucleotide polymorphisms, are a common form of genetic variation among individuals, and they can offer valuable insights into disease mechanisms or potential subgroups.1 Using FREP and SNP-seq, she aims to identify specific locations in genes that may be responsible for causing disease and autoimmune conditions.1 Both SNP-seq and FREP have been used on a larger scale to complement Genome-Wide Association Sstudies (GWAS).1 GWAS are performed by scanning genomes of multiple samples and then attempting to find genetic markers based on the population.1 Such tools can be used to better understand risk SNPs in GWAS, which generally are only able to provide candidate SNPs that may be involved in disease mechanisms. Dr. Wu’s particular project aimed to complement GWAS studies and translate the identification of loci, or areas on the gene, associated with a disease into understanding the disease’s mechanisms. To do so, they utilized SNP-seq to identify functional SNPs that bind regulatory proteins in samples from individuals with rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus (Image 2).2 By identifying these SNPs, researchers hope to eventually be able to develop novel therapeutics to potentially cure or treat conditions like the ones Dr. Wu is studying.1 To conclude the project, FREP was used to isolate and identify functional SNP-bound regulatory proteins from other proteins in the sample.2 The research team was effectively able to identify a panel of regulatory proteins that controlled the CD40 gene, which was identified as a risk locus in the previous GWAS studies.2 The project also found a previously unknown interaction between the genes rs8179673 and SATB2, of which, SATB2 is a binding protein that activates an enhancer in the immune system.2 The group validated their results with a variety of wet-laboratory techniques, such as CRISPR-Cas9, a genetic-editing tool.2 Using CRISPRCas9, vectors were implanted into cells that were then cloned. and amplified, which allowed the scientists to examine mutations in DNA fragments. 2 Their project was integral in concluding that SNP-seq and FREP are promising approaches for translating GWAS data into understanding
how diseases progress through population-level genetics and on a molecular level. 2 Dr. Wu is optimistic when asked about the future of research in statistical bioinformatics and computational biology. She believes that with the quick development and integration of computer science into biological questions, as well as open-source sharing of data, the door opens with a multitude of opportunities.1 She wants to look into the use of machine and deep learning in understanding sequencing data as well as the use of multiple levels of data (from single-cells to genome- wide studies) in understanding disease mechanisms and pathogenesis.1 With both students and collaborators, she hopes to lead the charge in computational biology and understanding how to not only effectively analyze available data, but to also do it in a way that develops user-friendly tools and furthers her contributions to the scientific research community.
Figure 1: Process of identification of singlenucleotide polymorphisms with sequencing. Image courtesy of Dr. Di Wu. References 1. Interview with Di Wu, Ph.D. 2/7/2020 2. Li, G.; Martínez-Bonet, M.; Wu, D.; Yang, Y.; Cui, J.; Nguyen, H. N.; Cunin, P.; Levescot, A.; Bai, M.; Westra, H.; et al. High-throughput identification of noncoding functional SNPs via type IIS enzyme restriction. Nature Genetics 2018, 50, 1180–1188.
Carolina Scientific Executive Board
Sophie Troyer Editor-in-Chief
Maia Sichitiu Design Editor
Sidharth Sirdeshmukh Editor-in-Chief
Divya Narayanan Associate/Copy Editor
Aneesh Agarwal Associate Editor
Andrew Se Managing Editor/ Treasurer
PAST EDITIONS OF CAROLINA SCIENTIFIC
Carolina Check out all of our previous issues atwww.carolinascientific. org. As the organization continues to grow, we would like to thank our Faculty Advisor, Dr. Gidi Shemer, for his continued support and mentorship.
scıentıfic Fall 2018 | Volume 11 | Issue 1
The Secrets of Space
—USING NUCLEAR FUSION DATA TO IDENTIFY NOVA EXPLOSION PRODUCT— full story on page 26
“The virtues of science are skepticism and independence of thought.” - Walter Gilbert
Image by Ildar Sagdejev, [CC-BY-SA-3.0].
Spring 2020 Volume 12 | Issue 2
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.