UTS Vol 10 (2019-2020)

Featuring Undergraduate Research from the 2019 Biological Sciences Student Research Showcase

Volume 10 2019-2020

m o r f r e t let Dear Reader,

R O T I D E E TH

In your hands rests the product of ten years of trial-and-error. For more than a decade, students in Saltman Quarterly have collectively been learning how to effectively communicate science using print, online, and in-person methods. Under the Scope in particular represents undergraduates highlighting research done by their peers; this volume marks the tenth year of coevolution between emerging biologists, writers, and communicators to synthesize concrete products reflecting the incremental yet dynamic nature of scientific research.

Whether it’s tracing molecular cues or cultivating traditional knowledge, science across fields and cultures is collaborative, community-driven, and, most of all, human. It’s not a perfect science; rather, methods and results continue to grow and change as new contributions arise. As undergraduate research on our campus rapidly increases in quality and quantity, so does the drive to investigate the underlying connections between seemingly-individual research projects. Through compounding processes over the past ten years, the scope of this publication and its creativity in multimedia storytelling have evolved to not only investigate the what and how of science, but also to consider who is involved, why we should care, and where we may venture next.

The scientific process seeks new discoveries, but existing findings must also be examined with a critical eye when generating new knowledge. Whether considering knowledge gaps about interactions between tiny microbes or about the complexities within healthcare systems at large, Under the Scope captures the projection of science

as increasingly cross-disciplined, imaginative, and inclusive. Novel research remains important in an ever-changing world, but deeper discussion of existing datasets often leads to uncovering abstract ideas that encompass the functioning of life at wider scales. Sharing this process of data-driven thinking–whether through writing, graphics, or everyday conversation–is imperative to breaking down barriers to science and create space for diverse perspectives in research; engagement, education, and outreach are key components of doing research itself. From doctors to museum curators, from journalists to primary investigators, from biology students to curious minds everywhere, science is for everybody.

In times both tranquil and tumultuous, science is a framework through which we seek patterns and understanding. Throughout this year of fluctuating circumstances, it has been a privilege and inspiration to work alongside my peers–researchers and communicators alike–and grow in how we make sense of our shared world. In the years to come, I am certain that our place within the symbiosis of science and its communication will continue to evolve.

With joy, I present to you Volume 10 of Under the Scope.

Arya Natarajan Executive Editor, Under the Scope 2019-2020

EDITORIAL BOARD Executive Editor Arya Natarajan Features Editor Andra Thomas Production Editor Julia Cheng Features Design Editor Khulan Hoshartsaga Head Technical Editor Salma Sheriff Technical Editors Juliana Fox Lynn Nguyen Noorhan Amani Max Gruber Rebecca Chen

Core Staff Editors Emma Huie Sharada Saraf Shreya Shriram Daniel Lusk Alejandro Dauguet Xaver Audhya Gayathri Kalla

HEAD ADVISORS

WRITERS

ILLUSTRATORS

James Cooke, Ph.D. Assistant Teaching Professor of Neurobiology

Vickie Kuo Julia Tu Varsha Mathew Alexandra Casison Dexter Tsin Shuhe Wang Ahsan Usmani Nikhil Rao Soha Khalid Sathya Krishnasamy

Varsha Rajesh Hannah Abraham Angel Rivera Sara Kian Phoebe Ahn Lu Yue Wang Cristina Corral

Jaime Estepa Student Engagement Coordinator Division of Biological Sciences

FACULTY ADVISORY BOARD Douglass Forbes, Ph.D. Suckjoon Jun, Ph.D. Carolyn Kurle, Ph.D Jill Leutgeb, Ph.D. Lisa McDonnell, Ph.D. Chih-Ying Su, Ph.D. Elsa Cleland, Ph.D.

PHOTOGRAPHERS Michael Endow Jason Dagoon Katie Clark Mark Jacob Sam Zilberman Bridget Spencer Anne Marie Berry

COVER ILLUSTRATION Sara Kian

TABLE OF CONTENTS ILLUSTRATION Cristina Corral

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ith the diligence and intrigue of a baker watching the delicate process of bread rising in an oven, a student researcher carefully monitors neuronal calcium ion fluorescence on a computer screen. At UC San Diego, neuroscience research laboratories are going against the grain and cooking up tremendous progress by investigating the neurochemical mechanisms that induce and accelerate Alzheimer’s disease (AD). AD is a degenerative neurological disorder characterized by the brain’s inability to retain memories and rationalize thoughts. The development and progression of AD is complex, impacted by factors such as environmental conditions and age. Genetic expression, the phenotypic output encoded by a particular gene of DNA, has a particularly powerful influence over the manifestation and progression of this puzzling disease. Similar to how small adjustments in ingredient types and ratios can produce drastically wide varieties of bread, slight changes in brain chemistry can induce different neurodegenerative disorders. Neurologists at UC San Diego work to develop symptom management models and long-term treatments based on genetic expression research to both extend and improve the lives of the millions affected.

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An image of a bread roll, representing the brain. Its structure and development can be altered to prevent Alzheimer’s Disease.

WHAT’S COOKING? AD develops as brain cells degenerate and their connectivities break down. The origination of the disease and the pathologies observed vary between patients, but the first visible signs of AD arise in the medial temporal lobe, a division of the brain essential for learning, recognition memory, and the processing of short-term memory into long-term memory. As a result, AD patients show progressively pervasive symptoms of memory loss, confusion, difficulties concentrating, and delusion, among the long list of other potential behavioral and social inhibitions. As AD progresses, the disorder spreads to affect other areas, such as the cerebral cortex. Interestingly, autopsies of the brain tissue in AD patients reveal a vital clue to the mysterious development of AD—small build-ups called tangles and plaques in the tissue. The tangles, composed of a protein called tau, replace nerve cells, while plaques, made of a protein known as amyloid beta, lie between dead or dying neural cells. Although these morphologies can be a sign of AD, their exact relationship to the cause of AD is unknown, making it a subject of deep scientific intrigue.

Taking on this interest, Kshitij Gaur, Silvia Viana da Silva, and Rina Patel of UC San Diego’s Leutgeb Laboratory investigated the relationship between the volatility of neuronal dysfunction and different protein types and levels in the development of AD. The functions encoded within genes are carried out by proteins. At the chemical level, a common strategy for protein research is injecting or evoking the production of the protein of interest in a test subject. Calcium imaging is used

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to visualize the activity of a neuron, and changes in calcium are thought to be when a neuron fires action potentials. They observed how A-beta expression changes neuronal function and how this ability influences the development of AD. Observations were also made through a miniscope, a tiny instrument inserted into the body to view internal parts and processes. To discover the effects of proteins on brain output capabilities, these student researchers also had their AD test subjects perform goal-oriented spatial memory tasks, such as navigating through mazes, and compared their abilities to that of the healthy mice. Note that while only humans are susceptible to AD, these transgenic animal models are used to mimic the progression of AD as a basis of neurobiological study. The students utilized these techniques and strategies to analyze the effects of mutant human amyloid beta precursor protein (hAPP), which regulates neural growth and repair, in mice. They concluded that this mutated version of hAPP causes significant spatial memory impairments and reduces neuron sizes. Gene-to-protein expression is a sensitive process. Kshitij Gaur notes that “We were simply using a slightly mutated form of this [APP] gene to generate an Alzheimer’s disease phenotype.” As scientists further investigate the relationships of protein types, common protein mutations, and protein levels on brain health, we advance our understanding of AD initiation and can develop preventative medications.

FLOUR POWER At the forefront of potential AD treatments is research on the relationship between gene-to-protein expressions and the progression of AD. Equate genes of DNA to a recipe for bread, proteins to flour and other baking ingredients, and brain health to the overall texture and quality of the baked bread.

With the correct recipe for delicious and fluffy bread, a baker knows the optimal ingredients and mixing ratios to bake the perfect loaf. Genes should encode the recipe for optimal brain health. Unfortunately, in AD patients, the genes that once encoded for healthy brains are damaged. A potential strategy for curing AD is to increase the expression of certain genes, similar to how adding white flour to a dense bread batter can create a softer and fluffier loaf.

However, just like the effects of gene expression, not all flour causes the overpowering results that cause bread to become brick-dense or even fluffy and soft. In Nigel Thomas Zhang’s research under Dr. David Salmon, Zhang delved into one specific gene: ApoE. This gene codes for the production of apolipoprotein E, a protein whose job is to combine lipids to make the macromolecule lipoproteins. Thinking about the possible differences that the apolipoprotein E ε-4 genotype could have on the progression of AD, his lab hypothesized that the presence of the apolipoprotein allele 4 (ApoE4) would be more prevalent among patients with early-onset AD, as the ApoE genotype is believed to contribute to AD’s severity, similar to that of the protein examined in the Leutgeb Lab. However, after using a statistical analysis test to compare

Genetic expression is defined by the central dogma, where DNA is transcribed to mRNA and then translated to proteins. In Dr. David Salmon’s research, early-onset and late-onset AD patients surprisingly do not demonstrate a significant difference in the expression of the ApoE4 allele on Chromosome 19.

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the severity of AD among patients with varying levels of ApoE4, they came to the unexpected conclusion that there was not a statistically significant difference in ApoE allele distribution based on the test’s results. The researchers compared Dementia Rating Scale (DRS) scores of patients, an assessment with five subtests that memory, attention, preservation, and construction.

Surprisingly, the ApoE allele distribution did not differ significantly in both early and late onset patients. Student researcher Zhang wants to explore this idea further, saying “other measures of cognition other than the score can be analyzed to see if there is a similar trend. Also the sample size can be increased by recruiting more participants since the original study had a fairly small sample size.” In the same way that the amount of all-purpose flour doesn’t significantly affect the texture of the bread as much as other flours,

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the expression of some genes may not make a significant difference on the symptom. It doesn’t affect the time at which the symptoms emerge.

JUST BEAT IT Nevertheless, researchers recognize that some genes have profound effects on AD development—gene therapy could be the cure. Gene therapy is the revolutionary technique of editing cells’ genetic code. This therapy is driven by vectors, small DNA molecules that are engineered to carry and insert new genetic material into cells. Vectors are activated by their promoters, short regions of DNA that control when and where within the organism’s DNA sequence that its associated gene is expressed. Vectors are a subject of heavy research because determining the types of vectors that function with high rates of success and efficiency can enable the development of the most effective AD gene therapy treatments. Vectors

CONCLUSION

The process of testing for the most effective vectors for gene therapies.

are judged by their abilities to enter cells and impact the accuracy of gene editing and strength of resulting gene expression. Nabta Laz, from UC San Diego’s Center for Neural Care—Tuszynski Laboratory, is part of the initiative to test existing vectors and to develop new vectors and investigate their advantages. Laz injects variant lipid acid vectors into mice and observes the resulting strength and specificity of gene expression through techniques, like vector staining for tracking and miniscope imaging and observation.

Combinations of different vector components are also effective. Laz determined that combining the promoter part of one vector with the remaining gene of another vector can lead to a particularly promising methodology for the delivery of gene therapy. The development of gene insertion and editing techniques, coupled with research identifying the relationships between different genes, can lead to breakthrough gene therapies for significant genes in AD development like the ApoE.

AD is a tragic and devastating disorder. Thankfully, the prevalence and baffling nature of this disease is heavily researched, and scientists recognize genetics and gene expression as one of the foundations to this disease. UC San Diego scientists investigate relationships between memory degradation and gene-to-protein expressions, ultimately driving the development of gene therapy techniques to potentially slow AD progression, reduce symptom outputs, and prevent AD altogether. The study of AD also supplements the studies of other neurodegenerative processes. Diverse research results–from studies investigating neuron health to those testing the efficiency of neurons under different environmental conditions–allows for greater progression of understanding the brain, enabling us to rise to the occasion and eliminate AD.

WRITTEN BY

Vickie Kuo & Julia Tu Vickie is a Human Biology major graduating in 2021. Julia is a Molecular and Cell Biology major graduating in 2022.

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THERE’S

MORE:

Female Underrepresentation in Medicine

Representation Matters: An increasing number of female scientists are taking charge and studying previously under-researched areas of women’s healthcare.

WRITTEN BY

Varsha Mathew & Alexandra Casison ILLUSTRATIONS BY

A

Angel Rivera & Varsha Rajesh

PHOTO BY

Katie Clark

man clutches his chest and teeters unsteadily in place. The audience gasps with fear, recognizing that the TV character is exhibiting the most well-known symptom of a heart attack—chest pain. Although chest pain remains as the one of the most common heart attack symptoms experienced by both men and women, women are more likely to experience symptoms such as neck or jaw discomfort, nausea, indigestion, or unusual fatigue when having an attack. Being able to recognize one of these lesserknown symptoms of a heart attack could be the difference between life and death for a woman.

Due to the lack of research being conducted on women’s health, many women have lost their lives to heart attacks, many of which were not properly diagnosed; in fact, according to the Centers for Disease Control and Prevention, 299,578 women died from heart attacks in 2017. As the number of women dying from heart attacks has increased, so has the number of women participating in research.

According to Dr. Christina Chambers, the recent surge of women in the scientific community has allowed for previously unexplored women’s health topics to be expanded upon and understood. For example, student researchers at UC San Diego have been focusing on the involvement of mood disorders in the fields of breast milk production and eating disorders.

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A mother and her newborn share a bonding moment during breastfeeding.

IS CHANGE ALWAYS GOOD? During pregnancy, a mother’s body begins to make hormones that play major roles during and after the pregnancy. These elevated hormone levels remain throughout the entirety of the pregnancy to aid the development of the fetus. However, in the 24-hour period after birth, the mother’s hormone levels suddenly drop to nonpregnant levels. For some new mothers, this abrupt drop can present issues such as postpartum depression and postpartum anxiety, two disorders that entail symptoms such as feeling depressed and having trouble forming an attachment with their newborn.

Conditions such as postpartum depression and postpartum anxiety are not uncommon or rare; according to the Cleveland Clinic, postpartum depression occurs in nearly 15 percent of births. However, despite the significant presence of this condition, research in the field of women’s health is still in its infancy. At UC San Diego, Shyla Butala, a third-year Physiology and Neurobiology major, presented research showing that expectant mothers exposed to marijuana (Cannabis sativa) had a higher risk of developing depressive symptoms, consequently increasing their risk of developing postpartum depression or anxiety.

Under the mentorship of public health epidemiologist Dr. Christina Chambers, Butala created a research project to answer the question of how a mother’s use of substances may affect her and her child’s health. Butala analyzed the results of an anxiety questionnaire filled out by mothers who enrolled in a human milk biorepository. After analyzing the questionnaire, which asked mothers to describe their substance usage and anxiety levels, Butala found that

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mothers who were exposed to marijuana had a significantly higher risk of developing anxiety and postpartum disorders. In order to combat the burdensome psychological symptoms of these disorders, many women continue their substance use after pregnancy. Studies have shown that this continued use might put infants at a higher risk for cognitive impairments, such as problems with memory and learning abilities. This poses a significant health risk for infants exposed to these substances through their mother’s breast milk.

GOT MILK? Babies who consume breast milk with traces of drugs like marijuana are exposed to harmful chemicals that pose significant implications to their well-being. In an interview, Dr. Chambers noted that, while it is well understood that drugs can be transferred from mother to child through breast milk, there has not been enough research done on the effects of substances such as marijuana or antidepressants on breast milk composition. However, the process of how drugs enter breast milk has been well-defined.

Drugs primarily enter breast milk through passive diffusion and secretory methods. When a mother consumes drugs, they enter her bloodstream and travel to her breast. Once there, the drugs pass through her alveolar cells, which secrete milk into the milk duct, a tube which takes the milk to the nipple for her infant to consume. This pathway allows potentially harmful substances such as tetrahydrocannabinol (THC) to enter the mother’s breast milk and subsequently enter her infant’s bloodstream. THC can stay in breast milk up to six days past maternal ingestion and enter the infant’s bloodstream in as short as ninety-five minutes. Knowing the

duration of different recreational substances’ presence in breast milk would provide immensely valuable information for mothers to make informed decisions on behalf of their health and their child’s health.

COMPREHENSIVE HEALTHCARE MATTERS Similar to the mental health disorders seen in postpartum women, conditions such as anxiety are also seen in women living with anorexia nervosa (AN). Nhien Nguyen and Rachel Weber, two undergraduate student researchers in Dr. PeiAn Shih’s lab at UC San Diego, studied elevated erucic acid concentrations in women with AN in order to determine if any of the most well-known unsaturated fatty acids correlated to any clinical phenotypes for AN. Erucic acid is a molecule that is broken down from fats.

Nguyen and Weber found that animals fed a diet high in erucic acid experienced body weight changes. The students recognized that increases in erucic acid levels in the body does not decrease post-meal anxiety in women with AN like it does in the control, and could be a contributing factor for the low body weight characteristic that patients with eating disorders exhibit.

Post-pregnancy symptoms such as attachment issues and depression worsen with the use of substances like nicotine and alcohol.

Although an effort to research the effects of prevalent conditions such as AN on mental health has been made, extensive studies on this topic are scarce. This scarcity has direct negative impacts on women; for example, the lack of studies on pregnant women with conditions such as AN severely limits the resources physicians can provide to new mothers. Improving women’s ability to make informed choices about the well-being of themselves and their child can be

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greatly improved with more research on the mental and physical challenges women experience during pregnancy. By gaining a deeper understanding of the cause or origination of AN, physicians are better equipped to treat patients with AN and provide them with the best outcome possible.

ARE OPPORTUNITIES KNOCKING? Scientists researching women’s health topics oftentimes encounter a multitude of problems during their research, such as unrepresented sample demographics. Butala also faced this challenge when completing her own study–she attributes this issue to women of diverse backgrounds not completing the surveys her study required. Because they did not complete the surveys, many of these women were cut from the research analyses; as a result, Butala was unable to make supported conclusive results. Through allowing any breastfeeding women to donate breast milk and complete the anxiety questionnaire, Butala’s study aimed to be as inclusive as possible. However, the results were not inclusive enough, as a majority of Butala’s sample consisted of Caucasian women. According to Dr. Chambers, the lack of non-Caucasian women in clinical studies is thought to be due to language barriers and lack of time.

Dr. Chambers agrees with Butala that a major limitation of Butala’s study lies in the sample population. Despite attempts to advertise her study through outreach programs, Dr. Chambers noted that many women of minority backgrounds remain unaware of this study because other members of their community are also uninvolved. Most clinical research participants enroll in studies after receiving recommendation from trusted family and friends. These opportunities are not

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as clearly presented in situations where one’s friends and family are unaware about such studies. In cases like these, the connection between the researcher and participant is lost, and the need to build a new network of trust between all parties rises. This can be done through an increased presence of female researchers, as the network between women involved in potentially helpful research studies and women who would benefit from those research studies has expanded. Thus, the increased presence of women in research will allow for better research outcomes and options for the general female population.

BUNDLE OF JOY Research conducted by the World Health Organization shows that 10% of pregnant women worldwide live with some form of mental illness, with a common disorder being depression.

During the postpartum period, this percentage increases to 13%. Although the effects of postpartum depression differ from mother to mother, common symptoms most mothers

Passive diffusion of chemicals through the cross section of blood vessels and alveolar cells in the breast allow for substances, such as THC, to permeate into breast milk.

suffer include having difficulties bonding with their newborn and feeling constant hopelessness. If left untreated, postpartum depression makes it difficult for mothers to care for their newborn and complete daily tasks.

By receiving the necessary help needed to manage symptoms of postpartum depression early on, mothers are better able to form stronger connections with their newborns, especially during breastfeeding. This can be an obstacle for both women who self-medicate with drugs such as marijuana to treat their mental health disorder(s), as these women have to consider if they want to continue to take medication and consequently put their child’s health at risk. For example, if a pregnant woman decides to continue ingesting antidepressants, she has to account for the implicated risks associated with her unborn child’s health. The difficulty associated with making healthy, well-informed choices for new mothers is primarily due to the lack of research being conducted on women’s health. By conducting more female-specific research, the scientific community gives mothers and all women the invaluable power of being able to make independent, wellinformed decisions about their health as well as the health of their child THERE’S MORE TO BE DONE Representation matters everywhere, especially in science, where the applicability of research is directly related to the population that was studied. As women make up nearly half of the world’s population it is necessary for studies that

research the effects of drugs on the human body to include women in their samples. In order to continue to broaden our horizons of scientific knowledge, we must discontinue the practice of extrapolating men’s health data to women, and instead expand the questions we ask to include a diverse range of women.

What makes science so versatile and powerful lies in our ability to make inquiries about topics that pique our interest and resonate with us. The results of such research have had an immense, positive impact on the female patients, as seen in the studies carried out by female student researchers like Shyla Butala, Nhien Nguyen, and Rachel Weber. Their contributions to science illustrate the importance of diversifying the research community; expanding the horizons of questions asked to develop our understanding of scientific knowledge and the world around us. One day, the increased female presence in scientific research might result in television shows being able to show a gasping man clutching his chest and a fatigued woman riddled with nausea, clearly conveying that both characters are experiencing a heart attack.

WRITTEN BY

Varsha Mathew & Alexandra Casison Varsha is a Molecular and Cell Biology major graduating in 2023. Alexandra is a Human Biology major graduating in 2020.

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magine one day, a large group of strangers drove to UC San Diego and occupied all the parking spots across campus, leaving no spaces for commuting students. Bacterial and parasitic infections function in a similar way. Bacteria and parasites fall under the umbrella term of microorganisms. They enter a living host at an infection site, multiply rapidly, and overwhelm the body’s natural defense mechanisms with their sheer numbers. By invading the host in this way, these microorganisms take away energy resources usually reserved for regular cellular work. Currently, the main weapon in the ongoing fight against bacterial and parasitic microorganisms is antibiotics.

While antibiotics have historically proven effective against certain microbial infections, there are some unintended consequences to this treatment. With the historical overprescription of antibiotics and the rapid reproduction rates of bacteria, many microbes have developed immunity to current treatments. The best-suited bacteria survive, creating a community of antibiotic-resistant microbes in an accelerated process of natural selection.

Some microorganisms repeatedly develop resistance to all antibiotics. Researchers at UC San Diego are currently trying to circumvent this issue and devise new methods to use these microorganisms to our advantage.

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Colonies of bacterial growth found on cheese.

ANTIBIOTICS: DEVELOPING NEW TREATMENTS FROM OLD ONES Rapid replication is an important facet of microbial activity that ensures their proliferation. Like any biological process, replication takes energy. The energy currency in most cells is called adenosine triphosphate (ATP). Take ATP away, and suddenly a bacterial cell lacks energy to replicate and dies. To employ this very concept in the fight against parasitic diseases, fourth-year Human Biology major Neda Abu-Gharbiyeh is exploring ATP-inhibiting treatment options for the parasite Giardia lamblia at Dr. Anjan Debnath’s lab.

G. lamblia is a parasitic protozoan that infects 280 million people annually. G. lamblia infections can result in a type of dysentery called giardiasis, an infection that can cause diarrhea and other gastrointestinal troubles. A study performed by Dr. E. Carter from The Hospital of Tropical Diseases shows that, as of 2017, the antibiotic [we/doctors] use to treat giardiasis is ineffective up to 20% of the time.

Abu-Gharbiyeh is exploring a novel course of treatment for giardiasis that works around its antibiotic resistance. Her research project focuses on inhibiting the growth of the G. lamblia parasite using bicyclic nitroimidazoles, which are chemical compounds derived from current antibiotic treatments.

During her research, Abu-Gharbiyeh used bicyclic nitroimidazoles to treat G. lamblia samples. If the results showed decreased ATP activity in the tested G. lamblia colony, that indicated that a specific compound was an effective drug.

To measure the compound’s success in ATP inhibition, Abu-Gharbiyeh used an ATP bioluminescence test, which causes ATP to glow when it comes into contact with specific chemical compounds. A device called a luminometer de-

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tects the ATP bioluminescence to track G. lamblia cell viability. Essentially, the fewer lights in a colony of cells after treatment, the more successful the compound is in killing the unwanted parasite. If the chemical compound tested in the lab successfully inhibits parasite growth, its ATP production would decrease over the course of the treatment, showing fewer lights in the colony overall.

Abu-Gharbiyeh has found four different bicyclic nitroimidazole compounds that showed a significant decrease in ATP activity, and thereby decreased viability, of the parasite samples. At this time, the lab will continue to pursue this promising line of research. The compound identified to be most potent will be tested for toxicity then further studied in animal models. According to Abu-Gharbiyeh, there are several potential drug leads that could culminate in the development of a new treatment for giardiasis.

While this research is rooted in expanding the current options for treatments of microbial infections, choosing to use compounds derived from existing antibiotics, other researchers are seeking more unorthodox methods. Namely, by collaborating with an age-old frenemy: viruses.

JOINING FORCES WITH THE ENEMY: ARE BACTERIOPHAGES SECRETLY OUR FRIENDS? Treating bacterial infections is tricky—what works to eradicate one strain may be ineffective for another. Since bacteria keep evolving resistance to antibiotics, undergraduate researchers in Dr. Rachel Dutton’s lab are getting creative to counteract them.

In Dr. Dutton’s lab, researchers hope to fight bacteria using bacteriophages, which are viruses that target bacteria.

Like all microorganisms, bacteriophages mostly have one

goal in mind: to multiply rapidly. However, because bacteriophages lack the biological components necessary for reproduction, they are forced to use bacteria as their hosts. Once the bacteriophage injects its genetic material into its host bacteria, it can remain for many replication cycles, making as many as a thousand replicates. The bacteriophage then lyses, or breaks open, the bacteria, releasing the viruses into the body and killing the bacteria in the process.

Beuffert, a bacteriophage that was discovered in a soil sample, was further studied through the Illumina genome sequencing tool. Genome sequencing is a process whereby the genetic information of a virus is mapped out. Through this process, the specific sequences of Beuffert’s DNA are listed and can be read like a book. Armed with this new information, researchers can isolate and analyze specific sequences of DNA or genes that have antibiotic potential.

So, scientists and bacteriophages have something in common: they both want to target and kill bacteria. Scientists have already figured out one way to edit genes to their advantage: CRISPR/Cas9, a gene-editing, cut-and-paste tool currently used to bind to and replace unwanted DNA sequences. Through genome sequencing, Beuffert was found to have similar protein components—namely, five of the same enzymatic domains as some CRISPR systems.

These shared enzymatic domains are a vital characteristic of gene editing tools that make identifying and grabbing onto DNA possible.

This discovery is promising for future bacteria-fighting. In the future, the genes that code for the significant enzymatic domains, such as the ones isolated in Beuffert, may

BACTERIOPHAGE

BACTERIA

PHAGE RNA BACTERIAL DNA

PHAGE PRODUCTION

REPLICATION OVER MANY GENERATIONS

BACTERIAL CELL DEATH

Bacteriophage (blue) vs. Bacteria (pink): Only one can win in this fight for existence.

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INTERFERENCE COMPETITION “WEAKER BACTERIA”

P.HAUSERI P.HAUSERI ATTACKS

P.HAUSERI HAS MONOPOLY OVER ATP RESOURCES

ATP CHEESE TIME

be employed to target specific DNA sequences known to be associated with bacterial infections. Though more research is required to test the effectiveness and isolate the specific functions of Beuffert’s enzymatic domains, there is potential to use the Beuffert bacteriophage in a technique analogous to CRISPR’s use today as a delete button for unwanted DNA sequences in host bacteria.

The Beuffert bacteriophage had its humble beginnings in a soil sample, but researchers didn’t stop there. Inspiration can come from any source, and one researcher found her inspiration in cheese.

AN UNLIKELY (BUT DELICIOUS) SOURCE Bacterial neighborhoods exist wherever bacteria are common—in underwater hot springs, in the gastrointestinal tract, and, at a slightly smaller scale, on cheese. When scientists take samples of microbes from their original ecosystems and study them in a lab, they are often unable to maintain the integrity of the environment necessary to keep all the microbes in the neighborhood alive.

Factors like humidity, temperature, and the presence of other organisms are difficult to maintain. This means that the bacteria studied on a petri dish are unrepresentative of the actual microbial community that would be found in

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nature, creating a problem known as the Great Plate Count Anomaly.

By using cheese as their chosen environment to study, undergraduates in Dr. Dutton’s lab can create a more natural environment in which they can study all the interactions between different bacterial species. Keeping a slice of cheese in a lab, with all its bacterial inhabitants intact, is much easier than keeping a slice of all the bacteria in a diverse, sprawling ecosystem. By using cheese, researchers can understand how bacterial colonies interact with each other more authentically and better study how molecular processes occur—like horizontal gene transfer.

While humans can only transfer genes from parents to children, bacteria growing in a populated bacterial community can transfer genes directly to each other through a process called horizontal gene transfer. Using horizontal gene transfer, the genes that have evolved antibiotic resistance can be shared among different bacterial strains. It’s good for the bacteria, but bad for the host. Thankfully, things are not always this harmonious in bacterial communities.

In any place where one bacterial strain lives, it’s likely that hundreds, or even thousands, of other strains share the

Interference competition between bacterial strains, shown here on a delicious battleground: a slice of cheese.

same neighborhood. Maybe you have that horrible neighbor who always takes your parking spot or maybe the group upstairs who throws a loud party every weekend. In these situations, the most drastic action might be sending them an angry note or calling in a noise complaint. Bacteria, however, take this to the extreme. In a process called interference competition, bacterial communities seek to reduce competition for energy supply by killing their neighbors.

Here lies another commonality—researchers and bacteria alike want to kill certain bacterial neighbors. The Dutton Lab thought it may be possible to use one bacterial strain’s competitiveness against the others and harness existing interference competition to kill a targeted bacteria known to cause infection. To isolate the cheese-dwelling bacteria that were the strongest and the best at killing their neighbors, the Dutton Lab ran multiple cultures from a whole smorgasbord of different types of cheeses.

The bacterial species Proteus hauseri was determined to be the best at interference competition, having successfully monopolized energy resources and flourished while other bacterial colonies died. The lab then used the Illumina genome sequencing tool and antiSMASH, a software that scans whole genomes, to identify two gene sequences in P. hauseri that are related to antimicrobial activity.

While the details regarding P. hauseri’s specific mechanism of lethality are unknown, these bacteria show potential for future antibiotic production. P. hauseri could even contain a new class of antibiotics previously undiscovered.

In the future, researchers hope to identify exactly which

genes of P. hauseri function as the antibiotic and how they can be isolated and used as treatments for microorganism infections.

AN ANTI-ANTIBIOTIC FUTURE? The bacteria proliferating today are the best of the best: the ones who have been optimized for their current environment. Bacteria have never been stronger, but then again, researchers have never been better equipped for the fight.

Humans and microorganisms will possibly be locked in the battle of simultaneous coevolution for a long time, but with the unorthodox research conducted daily here at UC San Diego, the goal is for scientific discoveries to keep up with ever-evolving health hazards. This research includes everything from analyzing bacteriophages’ potential use as a gene-editing tool, to searching for potential drug leads against parasitic infections, to using cheese to study bacterial interactions.

Throughout this evolutionary arms race, no idea is too crazy to pursue in the name of science and the optimization of human health.

WRITTEN BY

Soha Khalid & Sathya Krishnasamy Soha is a Human Biology major graduating in 2021. Sathya is a Microbiology major graduating in 2022.

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A New Tool in the

TOOLBOX How biomarkers are the next big break in preventive medicine research

WRITTEN BY

Ahsan Usmani & Nikhil Rao ILLUSTRATIONS BY

T

Phoebe Ann

PHOTO BY

Sam Zilberman

ypically, we think of medicine in terms of treating a sickness once symptoms have appeared. We catch an infection and visit the doctor to get treatment. However, with the rise of chronic illness, such as heart disease, diabetes, and cancer, there has been a growing discussion on preventive care. Preventive medicine relies on taking measures to avoid a health issue before it occurs in the first place. As an example, vaccines are designed to expose us to milder forms of potentially life-threatening diseases, thereby helping us develop immunity. Mammograms and PET scans are examples too, and they detect cancer before it becomes too severe.

For medicine to better implement preventive care, we need to develop quicker ways to detect disease.

For instance, how can we find signs of potential birth defects or premature aging? One powerful approach is using biomarkers. Biomarkers are labels that indicate certain biological phenomena, like disease or environmental exposure, just as a diligent reader may add sticky notes to the book they are engrossed in, or a police officer may activate the siren at the sight of a speeding driver. PET scans use radioactively labeled biomarkers to visualize the brain and locate tumors.

Biomarkers are an essential tool in research on numerous processes, such as aging and development.

Student researchers at UC San Diego have been working towards identifying novel ways biomarkers can be used to study these processes and their application towards preventive medicine.

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Immunofluorescent imaging of a mouse brain section. Images like this use biomarkers to visualize the proteins in the organ.

Taken at the Microscopy Core Facility at the La Jolla Institute.

MICRORNAS AS GENE EXPRESSION INDICATORS TO TRACK PREGNANCY The advent of ultrasound within the past half century has been monumental in helping doctors monitor a child during pregnancy. Creating detailed images of a fetus as early as 5 weeks old gives insight into how the child is progressing.

While ultrasound is useful, it can be difficult to pinpoint the age of the fetus in the first month of pregnancy. These earlier stages present a number of risks to the fetus, making it all the more important to monitor its development.

This is precisely what Goonja Shah, a Biochemistry and Cell Biology major at UC San Diego’s Laurent Lab, intendB to do. Her research uses microRNAs, or miRNAs, as biomarkers to create a model that predicts placental age, which is closely tied to the age of a fetus during pregnancy.

MicroRNAs are small strands of nucleotides (think to the As, Cs, Gs and Ts or Us in DNA and RNA) that serve as molecular switches, essentially turning genes “on” and “off.”

To turn a gene “on” means the product that the gene codes for is created. For instance, bacteria use certain proteins, called enzymes, to digest food. Normally, miRNAs would turn these genes “off,” since bacteria are not always eating, and the enzymes wouldn’t be made. However, when an organism eats, the miRNA would detach from the DNA, and the gene would turn “on,” producing enzymes so the bacteria can digest its food.

Shah used this knowledge to begin developing a model for placental age. Throughout the development of the fetus,

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We all have DNA in our cells that determines specific characteristics, such as left-handedness or green eyes. DNA uses a language of As, Cs, Gs, and Ts to “code” for these traits, just as books use a written language to communicate a story.

miRNA levels are constantly changing to switch “on” and “off” key developmental processes. Shah compiled data in hopes of creating a profile for what normal miRNA levels look like throughout pregnancy. With such a profile, doctors can detect whether the placenta is expressing a certain amount of a particular miRNA, which would correspond to a certain week of pregnancy.

Shah sampled blood from 125 pregnant women and sequenced the DNA using Next Generation Sequencing, a hyper-efficient method of sequencing DNA, to find key miRNAs indicative of placental age. She then examined DNA from mothers at UC San Diego, as well as mothers from a similar study in Israel, to find miRNAs associated with each trimester of development. She is still in the process of analyzing the data, but she has already found that among the twenty-six chromosomes in human cells, Chromosome 19 miRNAs show stronger expression in later stages of development.

The implications of such a model are enormous when it comes to preventive medicine. According to the American College of Obstetricians and Gynecologists, as much as 80% of miscarriages occur within the first trimester, often because of birth defects we currently have no way of tracking. Shah hopes physicians will use this model to determine if a pregnancy is going off track, averting a crisis in development before irreversible damage occurs. With pregnancy issues being a concern of many future parents, Shah’s project represents the focus on making the process of pregnancy safer for both mother and child.

PROTEIN TAGGING TO CREATE SNAPSHOTS DURING DEVELOPMENT Aside from pregnancy, scientists in recent years are also aiming to use biomarkers to track the development of the nervous system. Erika Barth, a Molecular Biology major at the Cline Lab at UC San Diego, analyzed how molecules are transported within the developing brain using protein

tags, another biomarker. Specifically, she uses NHS-Biotin, a compound commonly used to label various molecules.

Barth presents a new way to use NHS-Biotin for tracking these highlighted proteins as they are transported, using the visual system of the brain as a model to demonstrate its application.

First, NHS-Biotin is injected into the left corpus callosum of mouse pups’ brains. The corpus callosum is a bundle of nerves that connect the two sides of the brain. By injecting NHS-biotin at the left side of the corpus callosum, Barth can see how proteins move between the two sides of the brain through the corpus callosum. Barth imaged the pups’ brains both 24 hours and five days after the injection to view where the proteins were located at each time interval. This allowed her to visualize the proteins, labeled with NHS-Biotin, through a series of snapshots, recreating the journey of how the proteins traveled throughout the brain as the mouse pups’ brains developed. This is particularly significant, as it provides a new way to more closely study how specific proteins, which may be essential to normal brain development, are trafficked.

This newly developed technique presents a promising way to better understand brain development. Barth hopes to use this technique on diseased mice, giving insight on the signs of development of brain-related illnesses, such as schizophrenia. Such future endeavors would give researchers a better understanding of the causes of these conditions and serve as a starting point for preventive care relating to neurological illnesses.

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METHYLATED DNA: A POTENTIAL MARKER FOR PREMATURE AGING As we get older, it becomes more important that we monitor how our bodies are physically aging as well. However, monitoring old age goes deeper than just keeping track of wrinkles and counting gray hairs. It goes down to understanding how changes to our DNA can affect our likelihood of age-related complications like arthritis, cancer, and Alzheimer’s. By unlocking the mysteries of aging at the genetic level, it becomes easier to prevent age-related diseases before they get too severe.

In order to examine a potential cause of aging, Cloie Chiong, a human biology major, studied whether lengthy periods of time spent sitting play a role by using methylated DNA as her marker of interest. Methylated DNA is DNA with an attached methyl group, which is composed of one carbon atom and three hydrogen atoms. Methylation “turns off” the gene encoded by that DNA, similar to how miRNAs are used to regulate genes.

Research published in Nature suggests that obesity, caused in part by sedentary lifestyles, is related to increased DNA methylation. Similar research has further found that aging correlates with increased DNA methylation. Seeing DNA methylation as a unifying thread between sitting, obesity, and aging, Chiong hypothesized that increasing sitting time should also correlate with aging. This prediction was also rationalized on the basis that higher methylation has been found to correspond with higher insulin resistance, a major feature of diabetes. She formulated an experiment to test whether DNA methylation patterns are associated with sitting times. She factored out confounding variables

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FUTURE DIRECTIONS by observing that among her subjects, sitting times were not significantly different based on insulin levels, BMI, or demographics.

Chiong specifically tried to find the association by splitting women between those who sat for longer periods of time and those who sat for shorter periods of time. She then analyzed how DNA methylation patterns differed between those two groups and whether those patterns correlate with aging. While her analysis is still ongoing, Chiong hopes to potentially use DNA methylation as a way to link sitting time with aging.

Hopefully, Chiong’s work will further stress that the sedentary lifestyles we live today are causing harm in ways we wouldn’t expect, such as by accelerating aging. By combining our understanding of people’s lifestyles with biomarkers like methylated DNA, we open new doors in understanding aging. Beyond the physical signs, we can better determine if someone is on the path to developing arthritis or Alzheimer’s, whether they may be showing signs of a weakening immune system, and more. By identifying these kinds of age-related diseases earlier, we can address them earlier as well, perhaps by encouraging certain therapies or changes in lifestyle.

A human chromosome is unraveled to display the double-stranded DNA. Methyl groups attach to the nucleotides, acting as biomarkers in the process of DNA methylation.

Are biomarkers the next silver bullet for research in preventive medicine? While they may not be a catch-all for every issue, student researchers at UC San Diego have demonstrated new ways in which they can be used to help combat disease. We’ve seen how biomarkers could potentially be used to help monitor a child’s health during the first weeks of pregnancy, opening many doors to help prevent early miscarriages. At the same time, researchers are also trying to apply biomarkers to better detect signs of aging and deteriorating mental health.

Ultimately, the goal of this student research is to save lives.

It may take years for the medical field to use these results as the standard in medicine, but progress is being made.

By continuing research into this overlooked area, we can expand the reach of preventive medicine and, moreover, shift the focus of medicine from simply treating disease to stamping it out entirely.

WRITTEN BY

Ahsan Usmani & Nikhil Rao Ahsan is a General Biology major graduating in 2020. Nikhil is a Molecular and Cell Biology major graduating in 2023.

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Can You Read

MY MIND?

Researchers are using advanced imaging and recording technologies to study the relationship between neural activities and animal behavior.

WRITTEN BY

Dexter Tsin & Shuhe Wang ILLUSTRATIONS BY

O

Sara Kian

PHOTO BY

Mark Jacob

ften featured in futuristic fictions, mind reading unfortunately still has a long way to go before becoming an actual possibility. Neuroscientists have been trying to record brain signals to better understand behaviors and emotions and even predict them. Their work has led to breakthroughs that either record communication between neurons directly, via methods such as single-unit recording, or indirectly, via methods such as fMRI and calcium imaging.

There are millions of neurons firing in our brains every single second. Within a neuron, an electric pulse is generated by gradients of potassium and sodium ions flowing through channels across the cell membrane. When the signals reach the terminals of a neuron, a gap called the synapse prevents neighboring neurons from physically touching. To transmit the electric pulse from the first neuron to the subsequent one across this gap, neurons secrete small molecules called neurotransmitters into the synapse. Calcium ions flowing into the first–or presynaptic–neuron trigger the release of these neurotransmitters, and the receiving neuron generates electrical signals once it detects the neurotransmitters that have traversed the synapse. These electrical impulses happen all the time in the vast neural network that controls complex behaviors and emotions.

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Rats are a common sight in many labs, including the NEATLabs at the Veterans Affair Hospital. As model organisms, they provide researchers rich insights on neural functioning.

TRACKING NEURONAL COMMUNICATION Scientists have been puzzled for years on how to decipher messages sent by neurons, since neuroactivities are hard to detect without damaging the brain. According to a paper in Oxford Academic, the first attempt to study brain activity was in the 1880s. Italian physiologist Angelo Mosso invented the “human circulation balance” to study the brain. Mosso had a volunteer lie down on a wooden plank and carefully balance like a seesaw. After setting up, Mosso rang a bell. Mosso thought that, since the volunteer’s brain had to process the sound, it would require more blood, and therefore tip the scale toward the head’s side. Indeed, this is what Mosso saw. His discovery established one of the most important ideas of modern neuroscience: the brain is functionally subspecialized. In other words, a region of the brain will require a greater blood supply when the neurons in this brain region instruct physical actions.

But how do we measure blood distribution in the brain? This question was not answered until the late 20th century when scientists found that oxygenated blood and deoxygenated blood have different electromagnetic properties. Based on the theory that more blood is required when neurons are firing, modern neuroscientists invented functional magnetic resonance imaging (fMRI) in the 1990s. This was the first time a vascular response in the brain was detected non-invasively.

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The success of fMRI in clinical trials led to it becoming one of the most useful techniques to study human brains in the late 20th century. However, one limitation of fMRI is that there was a significant delay between blood redistribution and actual neural activities. Two undergraduate researchers at UC San Diego, Tianzhi Tang and Kimi Gabriella Taira, are trying to bridge this delay to more precisely decipher the relationship between neuronal activities and behaviors.

SINGLE-UNIT RECORDING AND OPTPGENETICS Tang did his undergraduate research in Dr. Dhakshin Ramanathan’s lab where, instead of studying the brain as a whole, he decided to focus on the activities of an individual neuron of the mouse’s brain. According to Tang, monitoring the activity of a single neuron can be achieved through implanting a microelectrode above the neuron. The electrical signals caused by sodium and potassium ion flow through channels in the neuron’s membrane are measured by the electrodes, therefore detecting electrical signals.

“The advantage of this neural recording technique is that it raises the resolution to single-neuron,” said Tang. Because electrical signals are directly picked up by the electrodes, the delay between the recorded signals and the actual signals is greatly shortened. Being able to take high-resolution recordings enables neuroscientists to study the function of a specific area of the brain.

Tang’s research does not stop here. He also wants to build up the causality between neural activities and behaviors. “We have solved the problem of measuring neural signals with a short delay and high resolution,’’ said Tang, “but what we really want to know is what behaviors are controlled by these neural signals.” To solve this problem, Tang successfully implemented a technology called optogenetics. Researchers genetically modified mouse neurons to express light-sensitive ion channels which allowed sodium ion influx once they sensed a specific wavelength of light. Once induced, this ion flow triggers neural electrical signals that control both the spiking activities of neurons and the physical behaviors of mice.

Tang gave us an example. A mouse’s ability to smell its predator’s odor is mediated by a group of neurons in the olfactory cortex of the brain. Activating these neurons that represent the odor of a predator would allow the scientists to determine if these particular neurons are necessary for the animal to detect a predator’s odor. Scientists introduce the expression of channelrhodopsin, an ion channel, to these neurons through genetic modification, and they surgically implant a thin fiber-optic tube above the olfactory cortex. The fiber-optic cables transmit light directly to these neurons, inducing electrical signals. In response to the light stimulus on its neurons, the mouse shows behaviors such

SODIUM ION SODIUM GATE LIGHT

Optogenetics enables us to manipulate mouse behaviors.

Mouse neurons are genetically modified to express lightsensitive ion channels that allow sodium ion influx at the sensing of specific light wavelengths. Sodium ions flowing into cells triggers neural electrical signals.

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as freezing—a common reaction when facing predators.

Even when predators are not physically present, the mouse follows neural stimuli; this occurrence of behavior paired with detection of electrical signals by single-unit recording helped Tang and other researchers begin to establish causality between neural activities and visible behaviors.

Neurotransmitters are released from the presynaptic neuron into the synapse when calcium ions flow in. The postsynaptic neuron then generates electrical signals once neurotransmitters are detected. Calcium imaging records the influx of calcium ions.

CALCIUM IMAGING: THE WALTZ OF IONS While we are fine-tuning single-unit recording, another question arises: neurons in the brain are usually spatially organized, so how can we capture the neural activity and anatomy of an area of cells? Vast networks of neurons contribute to the complexity of animal behavior, so measuring neurons at an anatomical level would create a more robust understanding of behavioral neuroscience.

Calcium imaging poses one solution. Considering that calcium ions are essential in neuron-to-neuron communication, scientists used the ions’ concentration to measure neuronal activity. Dr. Roger Tsien at UC San Diego revolutionized calcium imaging through the introduction of more sensitive chemical indicators to track calcium ions. Calcium imaging allows scientists to track neuron communication in real time under the microscope. Compared to fMRI and singleunit recording, calcium imaging provides a better temporal resolution than fMRI and a better big-picture view of neuronal connections than single-unit recording. As neural circuits and networks can be elucidated with the help of these calcium indicators, this technique provides another way to visualize the intricate mechanisms of single neurons driving complex human behavior.

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TAGGED CALCIUM NEUROTRANSMITTERS TRAVELING SIGNAL

PRESYNAPTIC NEURON

POSTSYNAPTIC NEURONS

UC San Diego student researcher Kimi Gabriella Taira in the Isaacson Lab uses calcium imaging to analyze the effect of fear conditioning on neural circuits in our auditory cortex. How the brain stores memory has remained one of the greatest mysteries of neuroscience. Researchers like Taira are interested in how certain neurons link up to one another when the animal is exposed to either appetitive or aversive stimuli. Taira uses one of the most commonly used experimental paradigms in systems neuroscience—a mouse hears a neutral tone and simultaneously receives an electric shock in the foot. The two concurrent events register together in the brain, making the mice anticipate the electric shock when it hears the tone again, turning the neutral tone into an aversive tone.

Taira not only focuses on the auditory cortex, which stores auditory information in the brain, but also the amygdala.

The amygdala is a region in the brain that primarily controls our emotional behavior, translating our perceived external environments into emotions. Previous studies have found that there are a lot of connections between the auditory cortex and the amygdala, which hints that the amygdala might be involved in the neuronal coding of sound. This is where calcium imaging comes into play. Fluorescentlylabeled calcium indicators are injected in the amygdala. Taira investigates the firing of neurons in the amygdala in response to a neutral tone versus the aversive tone; the tail shock is relayed from the mouse’s periphery through the spine to the amygdala. The captured data allows her to determine the neuronal ensemble that reacts a positive or negative cue, which will give her a specific neuronal representation. Using

calcium imaging, Taira’s research seeks to shed light on the amygdala’s neuronal architecture in various conditioning scenarios, ultimately contributing to our understanding of how memories, mediated by emotion, are stored in the brain.

A POTENTIAL FUTURE OF MINDREADING The emergence of fMRI in the early 21st century let us see the possibility of mind-reading in the future. Researchers like Tang and Taira are working on refining imaging technologies to make the dream of deciphering the brain come true in the near future. Technological advances in neuroimaging, such as single-unit recording and calcium ion imaging, may allow us to make more reliable measurements of brains. Future technologies like brain-computer interfaces or nanoparticles that help excite neurons could help further push the boundaries of neuroimaging with higher precision and less invasion. With the rapid research and development of new technology, mind-reading may become a viable reality in the near future.

WRITTEN BY

Dexter Tsin & Shuhe Wang

Dexter is a Bioinformatics major graduating in 2022. Shuhe is a Physiology and Neuroscience major graduating in 2021.

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CURATED BY

Arya Natarajan, Emma Huie, and Sharada Saraf Executive Staff, Saltman Quarterly 2019-2020

QUOTES from

QUARANTINE

perspectives from science communicators in the face of a pandemic Whether in a crisis or not, a mosaic of individuals mediates the day-to-day flow of scientific knowledge. Scientists and researchers serve as beacons of logic and knowledge. Doctors, nurses, and healthcare workers at the front lines share firsthand accounts of medical events. Communicators—artists, journalists, educators—rapidly adapt to using new mediums to make complicated information digestible and accessible. Together, these individual, overlapping nodes comprise systems of understanding that drive society as we know it.

With the surge of the SARS-CoV-2 virus, these systems have fallen under closer scrutiny. Science and ethics have become an increasingly visible part of everyday life, contributing to changes in how statistics and research are communicated. Engagement with this growing network of information may, understandably, be clouded by fear; this often leads to panic or indifference, disconnecting people from the science communicated by the news.

This has prompted the role of “educator” to expand beyond classroom walls. Many biology students did not anticipate being looked to by their families as the spokesperson of health measures. Now, more than ever, many rely on critical thinking exercises taught in the classroom when engaging in everyday conversations. The network of scientific knowledge is always evolving; effectively communicating its dynamic nature is difficult to begin with, especially when faced with a daily barrage of shifting media messages.

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When unmoving opinions are thrown into the mix, this process requires the additional step of balancing logic and emotion to open lines of reciprocal communication—we as students of science must take time to understand diverse perspectives emerging from a global health crisis. With possession of an academic understanding of science often comes condescension to those less well-versed in the subject, and this must be foregone in order to find a middle ground on which to cultivate shared understanding. Rather than simply quoting facts and statistics, educators must share tools for people to take ownership of their individual learning.

We spoke with four interviewees—three graduating students and one professor—about how their experiences with science and communication changed since the beginning of 2020. These individuals share stories of mitigating panic, adjusting to new environments, and changing perspectives—both of others and their own.

As students, we may not be ready yet to face the same set of problems as professionals in our prospective future fields do, but we must use our experiences to help uplift voices of those who know more than us. Acknowledging that we do not know everything is the first step to finding new solutions and making new connections. This is not a battle to reveal who knows the most; rather, it is a collaborative problem-solving process through which systems and networks of learning and communication will be re-envisioned.

Cristina Corral

THERE ARE ALSO ALL THESE VIDEOS AND ADVERTISEMENTS FOR OVERPRICED DISINFECTANTS, AND THEY FEED INTO A SENSE OF PANIC...YOU FEEL LIKE YOU’RE NOT PREPARED. searching things on the Internet; you’re learning from an insider perspective.

Cristina Corral, a General Biology major and SQ Illustrator, has a diverse volunteering, research, and science communication background. With COVID-19 interrupting previous plans, Cristina discusses her experiences moving back home, taking online classes, speaking about the pandemic with her parents, and adapting to an ever-changing environment.

1. WHAT WAS IT LIKE LEAVING YOUR PLACE IN SAN DIEGO? I’m very fortunate in the sense that I was able to say, “I’m going to drive back to LA and go back to my house,” because I still have friends that are at UC San Diego who are struggling to find other people to live with.

Suddenly, all their roommates moved out and aren’t going to pay rent anymore. I have so many friends who say, “I need to find someone to move in with me. Otherwise, I’m going to get evicted, and I don’t know where to go.” People are losing their jobs and they don’t have money to pay rent.

2. WHAT OPPORTUNITIES HAVE YOU HAD AS A BIOLOGY MAJOR, AND HAVE ANY OF THESE EXPERIENCES CHANGED DURING THE PANDEMIC? I liked the flexibility of being a general biology major. There are also so many fun classes to take, and there are a variety of topics with experts in the field. That’s something I don’t think you could get at most schools. I think meeting people who are in the field right now has been really helpful when asking questions. It’s something you can’t get from

UC San Diego has been really great in terms of resources for finding labs and things like that. When I was a freshman, I was hungry one day and I walked into Price Center and saw a sign that said there was a lab expo upstairs. I was like, “Yeah, I’ll go up there,” and that’s how I got into my first lab—I just walked into it. It’s insane how many different resources they have for biology students at this school. I don’t think you could get the same experience [during the pandemic] because everything has to be so structured now. Things can’t just happen, like when I found my lab by just being hungry and seeing a sign for a lab expo.

3. HOW HAVE YOUR CLASSES BEEN IMPACTED

BY THE PANDEMIC? Professors are having a lot of different approaches to things; some of them are doing asynchronous lectures, which is kind of hard for me.

Now you have to watch these lectures three hours before [the next lecture] because you have to catch up on all the material they want you to.

It’s weird in that sense, and I’m still having such a hard time keeping track… I’ve had professors already change their syllabus in one weekend. It’s a lot of trial and error at this point.

I signed up for all these labs and that was one thing I was worried about once they said we’re going to move online. Are they going to accommodate us, or are classes canceled? At least in the lab classes now, I’m not learning the same skills. We’re learning a lot more about the theory behind things. I would say it would be really hard for anyone taking a lab course that’s the first of the series. They will tell you that you’re prepared for future lab courses, but you’re not if you’re just seeing it all online. But, we’ve got to work with what we have.

4. HAVE PROFESSORS BEEN ACCOMMODATING? [Professors] have had asynchronous lectures for people in different time zones, and I think that helps people. Also, all attendance is op-

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tional; it isn’t great for someone like me, but I’ve been making myself go because I want to keep some sense of normalcy by sticking to [my schedule]. I would say most professors are being pretty accommodating about everything.

Hanna Richkind

I’m not complaining in any way because I know some friends who have it a lot harder. Like, their professors say, “we’re going to make [the tests] harder because we know that you guys are probably going to cheat.

We’re going to give you less time for your test.”

You tell yourself, “I’m not going to cheat.” But, you know that people are [cheating], especially when you have a curve in the class. Now, you’re being curved against people who are definitely just going to look up the answers on the Internet. Like, why am I even studying if everyone’s just going to cheat on this thing? If there’s a curve, I’m going to be screwed.

5. WHAT HAS BEEN YOUR EXPERIENCE WITH SCIENCE COMMUNICATION, FROM BOTH THE LISTENER AND SPEAKER SIDE? [As a listener], there is so much saturation of information. Every single story is related to the virus, which makes sense—it’s a global pandemic. I can’t wait for the day [the news] doesn’t say something about the coronavirus. There are also all these videos and advertisements for overpriced disinfectants, and they feed into a sense of panic…you feel like you’re not prepared. The virus is something that is changing every single day in terms of research, and it’s really hard to find credible sources right now. People don’t know what to trust.

[As a communicator], what has been happening recently is that my friends, who are biology majors, would correct their parents with knowledge from courses. But, their parents say, “I don’t know what you’re talking about, you need to respect me as your parent” and things like that. It’s a little hard, especially when you’re talking to your own parents, or people who are your elders, and trying to explain things. But, [your elders] will say, “it doesn’t affect me. It’s the world at large that has the problem.” But in reality, it’s all our problem.

We have to be really careful at this point…the necessary steps are to be informed, and to make sure that our parents understand why they should not be outside...to ask them, “Do you really need to [go outside]? Ask yourself twice. Is it really worth going outside and risking getting this terrible virus?”

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Hanna Richkind, a Human Biology major and Photography minor, is SQ’s Publicity Chair. Her quick wit and charm is recognizable anywhere, from the lab she works in to the on-campus market she manages. Here, she shares how the pandemic has affected her as a science communicator, educator, student, and friend.

1. WHAT HAS BEEN YOUR EXPERIENCE BEING A BIOLOGY MAJOR AT UC SAN DIEGO? I really was worried about being a biology major. When I first got to UC San Diego, everyone talked about how hard STEM classes were. One of the first things they tell you is, ‘only 30% of you are still going to be a pre-med by the time you’re a senior.’ So, it’s not a very supportive environment when you first get here, like, it’s very scary. But then, as you go look through it and you make friends along the way, it totally bolsters your confidence. Coming in as a senior, I feel very proud of what I’ve accomplished.

I am so grateful that I’m a biology major during this time. I have always been really interested in epidemiology and human disease, so all of my biology electives have been disease-related. Because of that, I think that it kind of helped [me] understand the pandemic as it was starting and where we are now. Before, I think there were people in two camps: there were those that said, ’it’s the flu. It’s nothing.’ The others were freaking out. Anyone that understood epidemiology, or at least had

4. DO YOU FEEL CLOSER OR MORE SEPARATED FROM PEOPLE?

THIS IS A TIME WHERE FACTS ARE REALLY GOING TO BE WHAT SET ASIDE THE PEOPLE WHO PANIC AND THE PEOPLE WHO ARE PREPARED. some sort of background (even if they weren’t bio majors), was in the middle, thinking, ‘this is something we need to take seriously, but don’t panic.’ I think that [my experiences] prepared me in a mental way for understanding what’s happening in the world and what steps to take.

2. WHAT HAS BEEN YOUR EXPERIENCE WITH ONLINE CLASSES? I just moved home and I’m with my parents. I haven’t seen them in so long, and I want to do all these things with them. But then, I’m like, ‘I can’t, I have to go study. I’m sorry.’ I’m in this mindset moving home where I think it’s summer break, but it’s not. We’re in the midst of Spring Quarter, so you kind of have to psych yourself out. I think [productivity] is really hard for a lot of people. Everyone’s got something that works for them.

Neither of the two classes that I’m taking require you to actually be there live. It’s all pre-recorded, so you could technically take this class in week ten and just do nothing for nine weeks. I can tell you that, being a student for four years, I know not to do that. If I were a first or second year, I would definitely be procrastinating more, so I worry for those kiddos.

3. WHAT WAS IT LIKE LEAVING YOUR APARTMENT? Right before the quarter, my manager [at the market] called me and said, ‘there are no more hours for students. We don’t even have hours for the non-student workers.’ Because I no longer had a job to make money, I couldn’t really afford to stay there. I was expecting to have another eight months of being in San Diego. Now all of a sudden, I’ve got 24 hours to go get my stuff and move out. It was kind of a whirlwind. It really threw me for a loop at first, and I felt really sad about it, but you have to roll with the punches. But, I think financially and health-wise, it’s much better for me to be with my parents.

I feel like it could really go either way, because my main contact is with my cousin and I’m an only child. We’re like the closest thing that we have to siblings. So, we’ve always stayed really close in touch, like messaging over social media almost every day. Having this pandemic going on, and knowing that we’re not going to get distant even though we’re stuck in our respective houses, has set up the stepping stone to have that firm base of family communication. I also have a roommate who is from the same hometown as I am. Having her in close proximity and being able to keep each other on track really helps. Also, having someone to look after and care about calms me down. It’s like this weird motherly thing. Having someone else care about my study habits and what I’m doing really balances [us] out. So if you have a buddy system for studying, even if you’re not in the same classes, it keeps you on track.

At the same time, [social isolation] is stressful. My grandma was just diagnosed with COVID-19. When my grandma doesn’t respond to a call or something, we all freak out, thinking, “what is she doing? Where is she?” When you don’t hear from [her], it becomes kind of anxiety-inducing—I can’t just drive over there and knock on the door.

5. WHAT DO YOU SEE AS YOUR RESPONSIBILITY WHEN CONSUMING MEDIA AND ALSO YOUR RESPONSIBILITY AS A PERSON IN A MEDIA ORGANIZATION? Everything has to be taken with a grain of salt. Even if it’s from the CDC, even if it’s from the World Health Organization, you have to be able to make your own informative judgments. Even though you are consuming what might be media that you implicitly trust because you think that it is the primary contributor or most unbiased contributor, it still has to be something that we look at with a critical eye.

I think science education is really important. This is a time where facts are really going to be what set aside the people who panic and the people who are prepared. People are scared. That’s when you get misinformation. That’s when you get people who have biased, unpopular opinions coming about. And maybe even spreading hatred, because hatred stems from fear. Being able to properly educate people in the scientific field, and providing them with the best information that you have and can get, is how you keep people well informed.

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Ahsan Usmani

THAT’S SORT OF ONE OF THE HARMS OF BEING IN A POSITION AS A SCIENCE COMMUNICATOR; IF YOU DON’T KNOW THE WHOLE STORY, ESPECIALLY ON SOMETHING AS BIG AS THIS, YOU MIGHT BE PERPETUATING THE PROBLEM. 2. WHAT HAS BEEN YOUR EXPERIENCE WITH CLASSES ONLINE? I don’t imagine people are excited about classes online, especially if they’re paying for in-class courses. I think online classes are good in theory, but it seems like at least half the classes you take right now are just pre-recorded lectures or lectures from a previous year.

Recently graduated, General Biology major Ahsan Usmani has been an Under the Scope writer for four years. As a science writer and current Teaching Assistant, Ahsan finds that the pandemic has been an opportunity to reflect on his responsibility as a science communicator, the importance of transparency during a crisis, and his passion for medicine.

[As a TA], I like the way I normally did [discussion] sections with people—often with small groups, and I would rotate to make sure people were doing things. In theory, breakout rooms should do the same thing.

But, you can only be in one breakout room at a time. In my last section, I was saying goodbye to everyone in one of the rooms, and by the time I got to the third room, everyone was gone. I was like “dang, I prepared my little speech on everyone’s future and it would be nice if they heard it.” I wasn’t looking forward to online classes at all, which is why I’m happy I graduated.

1. HOW HAS YOUR EXPERIENCE AS A BIOLOGY MAJOR CHANGED THROUGH THE YEARS, AND HAVE YOU EXPERIENCED ANY MAJOR CHANGES GIVEN THE PANDEMIC?

3. WHAT HAS BEEN YOUR EXPERIENCE BEING A SCIENCE COMMUNICATOR, BEFORE AND NOW, DURING THE PANDEMIC?

I think it’s only in these last few years where I really felt more like a biology major. This past quarter, I took a class on modeling biology. It was cool because it makes me think about biology not so much as, “protein A interacts with protein B, etc.” It’s more like molecules hitting each other, acting randomly. I think learning about biology in those contexts interests me–realizing that biology is sort of just like modeling what goes on. It’s not just “here’s exactly how it goes.”

The last four years at UC San Diego and doing stuff like SQ made me think more about how I can communicate. Going off of COVID-19, back in January, I was more in the camp of, “this whole thing will blow over.

We should keep our distance, wash hands, and it’ll be fine at the end of the day. For most people, it’s the flu. If you’re older, you should keep away.” That’s sort of one of the harms of being in a position as a science communicator; if you don’t know the whole story, especially on something as big as this, you might be perpetuating the problem. I thought, “COVID-19 isn’t a big deal. This is a contained thing.” The moment it wasn’t contained, I started looking at myself like, “you’re an idiot. Why would you say that?” I was sort of like “ah, I feel really stupid.”

Getting more into research is also something that transformed a bit over the last two years. Now with the coronavirus, one cool thing my lab is doing is that we’re remotely designing protocols, because graduate students are considered essential. I’m not really pipetting anymore, but at the very least I’m still running experiments.

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I’m still gonna do my part to communicate, but it’s definitely made me temper how I want to speak about these things. You’re never gonna be 100% right all the time, it just sucks to be wrong right now.

4. HOW DO YOU FEEL LIKE THE SCIENCE OF COVID-19 IS BEING COMMUNICATED IN THE MEDIA YOU CONSUME? I don’t think the current administration is doing a very good job of it.

[One side] is saying one thing, and then you have smaller interviews with Dr. Fauci and Dr. Birx saying something completely different. The communication is not really there. Then, the news is pretty much always just on COVID-19. I think it’s a tricky job; if you’re someone like Dr. Fauci, I think it’s a really tough position to be in. It’s just a really big data game and I think communicating on that is harder now because we’re trying to catch up.

I think that if anything during the pandemic inspired me, it’s that, despite the lack of resources, medicine is really working at its best right now. And, if I could be a part of medicine and try to help during this time, I’d want to do that.

Dr. James Cooke

If there’s one thing I learned through this whole thing, it is that there needs to be more transparency. If there isn’t, scientists can’t really do much. The best way I can put it is, even if the scientists are performing at their absolute best right now, if they don’t know what they’re dealing with, nothing’s ever going to come out of it.

5. ON A MORE PERSONAL NOTE, HOW ARE YOU HANDLING QUARANTINE? I think one thing I like is spending more time with family. On one hand, it’s really great–you get to see your family more. At the same time, this could be a long pandemic, and hopefully familial ties for most people are going to remain intact.

It’s a difficult thing to adjust to, but I feel like social distancing and staying home is a privilege and a responsibility. Essentially, all I can really do is stay at home, because I don’t want diseases to spread any further. And, I have the ability to stay at home without putting myself at a financial risk. It’s to benefit other people in society as a whole.

6. WHAT ARE YOUR THOUGHTS ABOUT BEING PRE-MED AND THE PROSPECTS OF BECOMING A DOCTOR AMIDST THIS PANDEMIC? I think this makes me more invested in medicine, because right now, the best I can do to help alleviate issues is to just stay at home. That’s the best I can do, within my capacity as a student. I think the fact that doctors are able to be their best in situations like these inspires me to be a doctor even more… to be a physician, to be in that situation where I can really help people and potentially save lives, or at the very least, have conversations on how we can best approach this pandemic.

Dr. James Cooke is an Assistant Teaching Professor at UC San Diego, where his research focuses on undergraduate student learning. Through trial and error in creating a dynamic and unique learning environment, Dr. Cooke ultimately hopes to improve students’ critical thinking skills and retention of course concepts, which in turn helps them grow into better scientists and educators themselves.

1. HOW HAVE YOU CHANGED AS A PROFESSOR IN YOUR TIME AT UC SAN DIEGO? My initial approaches and ideas about how to manage my classroom have changed since I first started here. [I did] a lot of group work [and] student-centered work in my first year. Results weren’t terrible but I got a lot of…constructive feedback about how UC San Diego ‘works’ from the students. So, I had to change my approach.

There’s robust literature on dealing with student and teacher expectations in the classroom. When there’s a misalignment of those things you get what’s called a cognitive dissonance, and I think what I was encountering was a lot of this. I would argue that I was using techniques

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WHAT ACTIVE LEARNING, STUDENT-CENTERED LEARNING REALLY MEANS IS GETTING STUDENTS TO THINK ABOUT THE MATERIAL MEANINGFULLY IN REAL TIME. SO, HOW DO WE DO THAT? that would drive better learning and better learning outcomes for my students, but if the students aren’t expecting or wanting that, then even great approaches may not lead to optimal learning.

[So] there’s been this evolution as I go of how I structure my classroom.

I have a bit of a reputation, which is good or bad, but… I think some of the folks know that when they get in they’re going to have somewhat of a different experience. And I try to spend a lot of time introducing why I teach this way and why we do these things… and since I’ve started taking this more methodical and explicit approach, things have been a lot smoother.

2. HOW HAVE YOU BEEN ADAPTING TO ONLINE TEACHING? There are ways to do [online teaching] to maximally engage with students. The truth is, I don’t have a lot of time to reconfigure my whole course...with my full-time job being compressed into half-time hours.

I’ve been tweaking lectures but still try to make time for students to think. What active learning, student-centered learning really means is getting students to think about the material meaningfully in real time.

So, how do we do that?

I’ve developed a lot of activities over the years to try and get at some of these key issues… I haven’t figured out a great way to get [UC San Diego students] to do group work [online], but I’ve said to them, here’s a question I would normally give, I’d like you to pause the video and take two or three minutes… I try to emphasize the importance of writing down answers, because what often happens is that folks will just skip through and not write down answers and just wait for me to [give] answers and then they go, “oh, yeah, I get it.” And that’s the trap, actually–the sense that one “gets” it, when one hasn’t tried to apply anything they know to a novel problem. There’s fairly robust literature that shows that [feedback] leads to better learning outcomes than just, “I get it.”

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[In current times], I’m trying to continue that approach of being explicit.

This would be a great opportunity to think of novel ways of engaging students and doing group work...but it’s difficult to do that especially taking flexibility into consideration. Pre-recording lectures and putting them up for students when it’s convenient for them is a really nice way to be accommodating, but it’s really difficult for me to do group work in that way. I haven’t fully reconciled that yet, and the truth is I haven’t had time to develop a meaningful way of fixing that issue.

3. DO YOU SEE YOURSELF CHANGING THINGS IN FUTURE ITERATIONS OF THE COURSE BASED ON WHAT’S HAPPENING THIS QUARTER? Assessments are definitely part of my research interests, I’ve been toying with group exams for a number of years now and getting some interesting results with that.

There’s really robust literature looking at the power of testing in driving positive outcomes for students. And it’s not just testing, it could be the studying for the test. That being said, I decided even before coronavirus came around, that this quarter, I was going to try a greater number of lower stakes assessments [as opposed to fewer higher stakes assessments] for a few reasons. I find that students at this institution have fairly high anxiety when taking tests, so how do we help that? There’s some evidence that greater numbers of lower-stakes tests can help... because you have more chances to redeem yourself.

[There’s also] information in the psychology literature that testing more frequently with feedback can drive better learning outcomes, so this quarter what I’m doing for the first time is weekly tests. There’s no midterms...and I drop the lowest score of the quarter. The final exam is summative [to let students show what they’ve learned], but not worth as much. I’d like to continue with that model moving forward. In class, I would not only have the test, but I would also take up the answers right after the fact, because the literature suggests that the timing of that feedback is really important.

4. HOW DO YOU SEE SCIENCE EDUCATION EXTENDING BEYOND THE CLASSROOM? I feel like our undergraduate curriculum is doing a good job. You don’t have to be a virologist or epidemiologist or microbiologists to understand benefits of washing your hands, or keeping distance, or even

broadly understanding how germs spread, and so on… so even a biologist who has never taken any of those relevant courses is capable of thinking critically about what [these measures] mean [and] why this is being implemented.

In talking to my family… they’re just not getting it. I am a little bit surprised when I talk to my family, and maybe this is just part of being in a family, like, I don’t know if you’ve had this experience where you say something really wise and nobody listens to you… my dad was bragging, “oh, I go to the drugstore every day at five before anybody’s there,” and I’m like, “why are you going every day?!”

There’s a lot of literature [that shows the use of] scientific evidence to support an argument when people who disagree aren’t using logic or reason is ineffective. If somebody has a belief or viewpoint that is removed from evidence, you can’t use evidence to crack into that, it doesn’t work.

One of the things we must teach well with our undergraduate population as a whole is reliable sources. We have pockets of populations, even with my own family, where people go to specific places for information that they believe regardless of any evidence you show them. We need to be training people to accurately identify reliable sources. Society is just full of bad sources of information… So how do you tell the good from the bad? And I think that’s part of our job as educators.

5. HOW HAS IT BEEN ADJUSTING TO AN ENVIRONMENT NOT NECESSARILY CONDUCIVE TO TEACHING? The university really has been wonderfully supportive… [in terms of productivity] there’s this internal motivation, too. I didn’t get into this job to

YOU DON’T HAVE TO BE A VIROLOGIST OR EPIDEMIOLOGIST OR MICROBIOLOGISTS TO UNDERSTAND BENEFITS OF WASHING YOUR HANDS, OR KEEPING DISTANCE, OR EVEN BROADLY UNDERSTANDING HOW GERMS SPREAD, AND SO ON… SO EVEN A BIOLOGIST WHO HAS NEVER TAKEN ANY OF THOSE RELEVANT COURSES IS CAPABLE OF THINKING CRITICALLY ABOUT WHAT [THESE MEASURES] MEAN [AND] WHY THIS IS BEING IMPLEMENTED.

do the least amount of work that I possibly can, and you wanna put the best product forward.

The truth is, [online platforms] aren’t a great way to have assessments, because there are academic integrity issues [and accessibility issues].

I’m doing what I can… if I had more time, if I were more creative, if I were more clever, I could come up with something… but the truth is I just don’t have the bandwidth right now to dedicate to weekly tests of that quality.

You have to kind of almost forgive yourself for shortcomings you see in your class. It’s really frustrating, honestly, especially when you see it as plain as the nose on your face, like, this is a problem and glaring hole in my course. I think all of us who are teaching this quarter are all dealing with this issue of how do we do a good job of rolling out something that’s high quality, that’s rigorous, that’s worthy of the standards of UC San Diego but doesn’t drive us into the grave.

6. HOW ARE YOU FINDING BALANCE WITH TRANSFORMING STANDARD RIGOROUS CURRICULUM INTO MORE FLEXIBLE FORMATS? Anxiety levels, stress levels…they all have impacts on education because they impair ability to prepare, ability to study, ability to stay on top of things. At the start of a quarter, I put out a call for students to share one thing they want me to know about them. One person said, “I’ve cried every day since school closed down, my father is an emergency room physician...I’m concerned for my family, I’m concerned for my father,” and… you know, they are scared. And rightly so.

And so you have people who are dealing with a lot of emotional stuff that is very real and very understandable. And from a pragmatic side of things, one person emailed me today and said, “hey, I finally got Wifi in my house!” and I was thinking, “well, okay, I definitely lead a life of privilege because I haven’t lived without Wifi in a [very] long time.”

These are real problems… I don’t have all the solutions, but the best thing to do is just be accommodating in the way you assess folks. We want to be rigorous but we also want to be understanding, equitable, and inclusive. You just have to do your best, and it’s gonna be messy… but we’re all in this together.

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Under the Scope

Division of Biological Sciences University of California San Diego sqonline.ucsd.edu