Uts vol6

Undergraduate Research Magazine with Proceedings of the Biological Sciences Student Research Showcase 2015

Saltman Quarterly Volume 6 2015-2016

LETTER from the

EDITOR Decay.

It seems so odd that the theme of Volume 6 of Under The Scope would be something that many believe is the very opposite of biology — the very opposite of life.

But decay is what gives birth to new life.

When it comes to our research, we encounter forms of “decay” as we undergo the scientific process. The low points in our experience hinder our progress to scientific discovery, but in turn, lead to new ways of thinking, approaching problems, and fine-tuning our path to the breakthrough.

I, like many of the undergraduates that conduct research on our campus, have dealt with troubleshooting an experimental design until every last kink is smoothed out. When our test cultures die instead of expressing antibiotic resistance, or when an unexpected algal bloom disrupts pH measurements, it’s easy to view any misstep as the end. But these obstacles are what allow us to reevaluate our thinking and cultivate pathways to successful scientific outcomes. Decay in our scientific work gives us the pause we need to reevaluate our methods — to take the good elements from our previous plan and weave new ideas in to create something better.

Just like the fungi decompose soil organic matter and use the nitrogen left behind to fuel their own life, the staff behind Under The Scope went through a similar process to create the magazine you hold today. Our writers spent close to ten months in discussion with our editors, finding ways to craft better stories from their drafts — you can see this process by scrolling through any story’s Google Doc documents and taking in the multitude of comments and conversations between writers and editors. Walking into our office, this cycle of creative decay and rethinking our choices for our Production team is apparent in the scraps of paper with mock layouts and illustrations that didn’t correctly convey the story. It’s only because of those 3 a.m. nights messing with InDesign that we have a captivating blend of words and images. Our creative process — the process of letting ideas decay until finding something that lights up the pages — is what leads to Under The Scope Volume 6.

From the human body to model organisms, and cancer to coastal reserves, everything experiences decay. But the stories we bring you show how our undergraduate researchers find something new — something lively — within this process.

It is with great pride that I present to you Volume 6 of Under The Scope. We hope that the stories behind our undergraduates’ research bring you life.

Yaamini Venkataraman Executive Editor, Under the Scope

EDITORIAL BOARD

HEAD ADVISORS

FACULTY ADVISORY BOARD

WRITERS

ILLUSTRATORS

Executive Editor Yaamini Venkataraman

Steven Wasserman, Ph.D. Professor of Cell & Developmental Biology

Eric Allen, Ph.D.

Rachel Sebastian

Connie Mach

Timothy Baker, Ph.D.

Jaidev Bapat

April Damon

James Golden, Ph.D.

Nicki Guivatchian

Grace Lo

Suckjoon Jun, Ph.D.

Kevin Chau

Youree Choi

Jill Leutgeb, Ph.D.

Stephen Calderon

Steven Wasserman, Ph.D.

Joyce Sunday

James Wilhelm, Ph.D.

Jordan Setayesh

Martin Yanofsky, Ph.D.

Rithvik Shankar

Elvira Tour, Ph.D.

Rashi Saxena

David Holway, Ph.D.

Samantha Madala

Features Editor Arushi Atluri Production Editor Madalyn De Viso Features Design Editor Sarah George Head Technical Editor Hanna Tran Technical Editors Maxwell Ruckstuhl Denice Belandres Shuen Sun Sara Hakim

Hermila Torres Manager, do/Bio Center

STAFF ADVISORS Madeleine Picciotto, Ph.D. Director, Writing Center

COVER ILLUSTRATION April Damon

TABLE OF CONTENTS ILLUSTRATION Connie Mach

TABLE of CONTENTS 10

Probing the Possibilities in Cancer Prognosis Stephen Calderon and Kevin Chau

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The Backbone of Research Samantha Madala and Rachel Sebastian

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Coast to Coast Rashi Saxena and Joyce Sunday

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Losing Control: Afflictions of Mind and Movement Nicki Guivatchian and Rithvik Shankar

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Model Science with Model Organisms Jaidev Bapat and Jordan Setayesh

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The Backbone of Research

By Samantha Madala and Rachel Sebastian Cover and Illustrations by Connie Mach

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here is an affliction that can paralyze anyone, even Superman. This danger isn’t magical like Kryptonite, but it puts everyone at risk. This threat of paralyzing power is known as spinal cord injury (SCI). Actor Christopher Reeve, the Superman of the 1970s, damaged his spinal cord in a severe horse-riding accident. Because of this injury, Reeve was never able to walk again. What is it about SCI that makes even “Superman” vulnerable to losing the core human feeling of sensation? The spinal cord, a tight bundle of nerves inside the spinal column, is the partner to the brain in the human central nervous system and, most importantly, serves as a vital link between the body and the brain. Though this nerve channel is crucial to human function, surprisingly little is known about treatment if it is damaged.

UC San Diego, undergraduate students are also getting involved in the investigation of the mysterious spinal cord.

IMPROVING METHODS TO UNDERSTAND SPINAL CORD CELL MECHANISMS

The spinal cord is composed of neural cells, called neurons and glia, and nerve pathways, called axons, that extend from the brain to the lower back. Each spinal nerve contains nerve fibers that correspond to certain regions of muscle and skin. Cellular circuits between these neural cells and their corresponding body parts influence human sense and function through communication to and from the brain and parts of the body. One method used to better understand these cellular circuits is fluorescence imaging, which involves utilizing fluorescent dyes on proteins as labels for observing dynamic molecular structures. Fluorescence imaging in mice allows experimental observations that would otherwise be too dangerous to observe in the spinal cord, such as optical recording of protein expression using voltagesensitive dyes, gene expression, and the molecular activity in cells and tissues. However, factors involving natural motion, such as heart activity, respiratory cycles, and muscular tone, can corrupt the quality of fluorescence imaging. UC San Diego undergraduate student Nima Michael Assad conducted research attempting to improve fluorescence imaging methods in the Nimmerjahn laboratory at the Salk Institute Waitt Advanced Biophotonics Center.

The mystery shrouding the mechanisms of the spinal cord is due largely to the dangers in operating on these indispensable nerves. However, advancements in imaging technology, such as magnetic resonance imaging (MRI), have progressively unraveled the mystery of treating SCI. MRI evaluation of the spinal cord shows possible sources contributing to neuronal loss, the possible mechanism of injury, and the areas of spinal instability. These advancements extend to some of the greatest clinical breakthroughs, such as the application of stem cells to SCI. Through research on the regenerative mechanisms of the spinal cord, neurobiologists are gaining a better understanding of how to improve treatment for patients with SCI. Here at

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Fluorescence imaging is a technique used to visualize the nerve fibers. Imaging methods allow researchers to examine cellular functions as well as gene expression.

Assad’s project aimed to assess and enhance current imaging methods for studying spinal cords in mice at the cellular level. His goal was to create new techniques to compensate for the motion artifacts, errors in the images produced by the mice’s biological activities such as breathing and digestion, in order to directly examine cellular signals with less background noise. Typical algorithms currently used to correct for these motion artifacts, such as TurboReg, are not very effective in reducing the

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interference in the images because of low signal-to-noise ratios. That is, the motion artifacts may not produce a signal that is strong enough to be automatically rectified by conventional algorithms. In his research, Assad employed novel computational methods to determine the shortcomings of current algorithms and to better quantify imaging data.

Using MATLAB, a technical computing language, to analyze images of cellular activity within cells derived from mice spinal cords, Assad explained that he “tried to identify anchors in the images which would reflect motion [...] to look at the anchor and say the frame has been distorted.” By improving the imaging methods we use to study cellular activity in spinal cords, Assad’s research plays an important role in increasing the accuracy of imaging used in future spinal cord studies. His next steps would be to address motion artifacts produced by conscious animal behavior, such as sudden movements or shifts, rather than those created by autonomic bodily functions.

IMPROVING TREATMENT FOR SPINAL CORD INJURY

Spinal cord injury occurs when the vertebrae, the bones of the spinal column which normally provide protection, are broken or dislocated. This can put pressure on the spinal cord.

Damaging a section of the spinal cord means impairing the specific muscular functions linked to that section. Treatment for SCI is complex because neuron damage may occur not only

during the injury, but also after the injury. The environment of the spinal cord changes over the weeks and months following injury. During this time, three events may occur. Firstly, SCI causes the excessive release of neurotransmitters, which kills neurons. Secondly, SCI to the brain may cause the blood-brain barrier to break down and cause an excessive influx of immune cells, which damages spinal cord tissue. Finally, injury-induced production of highly reactive chemicals can overstimulate and kill neurons beyond the injury site. Thus, various therapies have been created to address the different kinds of damage at each stage of the injury. Current research on spinal cord repair focuses on four key goals: neuroprotection (protecting remaining nerve cells from further harm), regeneration (stimulating regrowth of nerve cells), cell repairing (replacing damaged cells), and retraining central nervous system circuits to restore body functions. Anael Shaddai Rizzo, a fourth year undergraduate UC San Diego student, has been working alongside postdoctoral fellow Jennifer Dulin. Their research involves regeneration of nerve cells in the Mark Tuszynski lab at UC San Diego’s School of Medicine Center for Neural Repair.

Rizzo’s research focuses on the corticospinal tract (CST), which transports electrical impulses from the brain to the spinal cord and is responsible for fine motor control that can be impacted

by SCI. So far, researchers have not been very successful in regenerating the CST in patients, but recent studies have reported success in implementing neural stem cell (NSC) grafts to

Neurons on different locations of the spinal cord carry signals to different parts of the body. The divisions include cervical, thoracic, lumbar, and sacral spinal nerves. The cervical spinal nerves, for instance, control signals in the head, neck, shoulders, arms, hands, and diaphragm.

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target and rectify severe SCI. NSC grafts facilitate transmission from neurons above the spine to regions below the lesion site. These NSC grafts have demonstrated strong resilience by effectively developing into mature neurons throughout the central nervous system, which is essential to successful stem cell utilization. Nevertheless, even though CST regeneration has been demonstrated in the NSC graft, patients did not demonstrate any improvement in performing motor tasks.

Researchers’ long-term goal is to use this procedure, along with gene therapy, to further promote the regeneration of CST neurons and restore motor function.

Rizzo’s research entailed utilizing the DCCdp1 gene to incite and sustain the regeneration process. DCCdp1 is an active, pro-growth form of the DCC gene, which has been linked to tumor suppression in colorectal cancer. Rizzo aimed to facilitate regeneration by overexpressing this pro-growth form in the grafts placed in SCI sites derived from rat spinal cords and observing the grafts for changes after six weeks.

Rizzo’s research is ongoing, and if her results are positive and successful regeneration occurs, these methods have the potential to be used as a viable new strategy for treating SCI. Working at the Masuda laboratory, UC San Diego undergraduate student Kevin Cheng also designed a research project to study spinal injury. Cheng focuses on bone loss induced by prolonged exposure to microgravity, or limited-gravity, conditions. In outer

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space, astronauts need to take measures to prevent bone damage that occurs as a result of being in a limited-gravity environment.

Gravity places necessary stress on bones to keep them in place.

Spinal bone loss, especially, can increase astronauts’ risk of sustaining injuries when carrying out routine procedures back on Earth. However, not much is known about the extent of bone loss caused by prolonged exposure to microgravity or about the adaptive biological changes that may occur within an astronaut’s body in response to space conditions.

To investigate these potential biological changes, NASA collaborated with the Russian Institute of Biomedical Problems and launched the Bion-M1 mission. One of the objectives of the mission was to study bone loss in mice spines without the countermeasures, such as structured exercise training, usually taken to mitigate the adverse effects of extended exposure to microgravity conditions. Cheng aimed to study the results of this mission, and hypothesized that being subjected to microgravity conditions for long periods of time would result in lowered bone mineral density (BMD), in addition to changes in bone structure. Cheng conducted Micro-CT analyses on mice spines, which are small-scale CT scans that result in threedimensional images of the spines. He found that the mice’s lower backbones exhibited significant bone morphological changes, as well as lowered BMD after being exposed to microgravity for 30 days, indicating that bone damage occurred. If further exposed to microgravity conditions, severe spine degeneration

could result. Ultimately, Cheng quantified significant changes in the spine, and his findings can be used to prompt better countermeasures for microgravity conditions.

WHAT RESEARCH IN SPINAL CORD INJURY MEANS TO US

Before World War II, a person affected by SCI faced certain death because little was known about treatment. The advances in research have not only helped lengthen patients’ lifetimes, but also improved rehabilitation. The progress of regaining some sensation after being paralyzed is made possible by research like that of Rizzo’s on regenerating axon connections. Developments in research to understand neural mechanisms, like those conducted by Assad and Cheng, are tied to developments in treatment. Developments in rehabilitation not only benefit patients with SCI, but also future physicians. A greater knowledge of neuroprotection, cell regeneration, and cell replacement will assist in spinal surgery and treatment of paralysis.

The unique structure of neurons allows electric signals from the brain to be carried to parts of the body.

Networks of neurons connected together are what compose the spinal cord. research in SCI is knowing that, in spite of any failures, we are going to reach some kind of breakthrough that ensures that we won’t need Superman to save the day from SCI.

For researchers, it is not just about trying to better understand the mechanisms of SCI; it is personal. For Rizzo, working in her lab meant “seeing individuals who are not only brilliant, but wholeheartedly invested. I work with talented scientists who are relentless in their aim to revolutionize the field of SCI, to ultimately pave the way to find a cure to SCI.” As exemplified by Assad, Rizzo, and Cheng, researchers in SCI demonstrate a special kind of drive, one motivated by more than just scientific curiosity. The beauty of

WRITTEN BY SAMANTHA MADALA AND RACHEL SEBASTIAN. Samantha is a General Biology major graduating in 2019.

Rachel is a General Biology major graduating in 2018.

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Probing the Possibilities in Cancer Prognosis

By Stephen Calderon and Kevin Chau Cover and Illustrations by April Damon

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ETHANOL ENCOURAGES EXPRESSION OF MICRORNAS

he human body is constantly becoming bigger, stronger, and more efficient as it develops into adulthood. Cells die and reproduce in a cycle regulated by the universal blueprint of life: DNA. But what happens when this cycle doesn’t go according to plan? What if cells keep multiplying, unchecked?

This is the basis of cancer, one of the leading causes of death in the world and the target of a multibillion-dollar research effort.

HNSCC is a cancer of squamous, or epithelial, cells that is found on the outer layers of skin and on mucous membranes.

These moist membranes are found in various body airways, which include the mouth, throat, and nasal cavities. Through years of research, alcohol consumption has been established as a risk factor for HNSCC. However, the molecular basis of the development of alcohol-related HNSCC remains poorly understood. One hypothesis concerns the role of ethanol in this cancer’s development. Alcoholic beverages contain ethanol, also known as ethyl alcohol or drinking alcohol, but this chemical does not seem to be directly responsible for HNSCC. However, metabolism of this chemical in our bodies produces an intermediate, acetaldehyde. This molecule is thought to be a carcinogen, a substance capable of causing cancer. It may be that this intermediate, rather than ethanol, is influential in the development of HNSCC.

A number of theories arose to describe the cause of cancer.

Doctors in the 16th century first described cancer as an infectious disease. In the 19th century, cancer was thought to be caused by extreme trauma or mortal injury. Now, it is known that cancer is caused by mutations that alter how cells grow and divide.

Because cancer is so complicated, many researchers are looking into different avenues to understand this broad disease, such as working backward from how the cancers manifest. This way, they can follow cancer’s progression and understand the intricate mechanisms of its development. This in turn gives researchers and patients a sense of what to expect as the disease progresses, thus opening up a new avenue for preventative care. Current research concerns the mechanistic understanding of cancer development and novel predictive advancements that have shown potential to revolutionize cancer medicine. Here at UC San Diego, several labs have made great strides in studying the mechanisms behind the development of cancers, specifically head and neck squamous cell carcinoma (HNSCC) and melanoma, and their implications in the prognoses for patients with these diseases.

UC San Diego undergraduate Maarouf Saad is working with an Associate Adjunct Professor in the Department of Surgery, Dr. Weg Ongkeko, in exploring the role of microRNAs (miRNAs) in the pathogenesis and progression of HNSCC as well as elucidating how ethanol’s role in that regard. In the body, miRNAs regulate gene function and are complementary to messenger RNAs (mRNA) that encode proteins. miRNAs correspond to certain sections of the mRNA. Specifically, the binding of miRNAs to

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epithelial cells with ethanol in vitro (in a laboratory vessel). The same process was done with acetaldehyde. Promising miRNAs at this stage were tested for their effects on cell replication and tumor development, sensitivity to the chemotherapy drug cisplatin, and their effects on genes that would eventually lead to cancer development.

Ethanol and its metabolic derivative, acetaldehyde, have been increasingly associated in the development of head and neck squamous cell carcinoma. mRNA regulates gene expression. “Typically we have DNA to RNA to protein. But then we have some of the non-coding RNA [e.g., miRNAs] with different regulatory roles,” Saad states. “We want to find some of these non-coding RNAs that play a critical role in potentially regulating the progression of these diseases.”

Saad collected the RNA sequencing data (a method used to quantify genetic expression by looking at RNA) of 136 HNSCC patients and compared over 1,000 miRNAs “between drinking and non-drinking cohorts.” The miRNAs observed in the clinical patient data through RNA sequencing were verified by treatment with both ethanol and acetaldehyde. This was done by treating

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Eight miRNAs were shown to be upregulated, or have increased activity, in alcohol-associated HNSCC. Of these eight, the two miRNAs that most consistently followed the predicted effects of treatment were further studied. Overexpression of these two miRNAs led to the induction of an anti-cell-death gene BCL-2, causing the proliferation of the cancer. Saad concluded that excessive alcohol consumption induces the overexpression of these miRNAs, contributing to the development and progression of HNSCC. He further states that research into miRNAs would prove useful in understanding this particular cancer, and is possibly translatable to other cancers as well.

MODERN MARKERS IN MELANOMA

UC San Diego researchers are also looking for significant methods to predict cancers. Lawrence Liu, a recent UC San Diego graduate who has worked with Associate Adjunct Professor, Dr. Pradipta Ghosh, in the Department of Medicine is one such researcher. In Ghosh’s lab, Liu looked for novel markers in blood that correlate with the prognosis of melanoma, a type of cancer that develops in pigment-containing skin cells. Recent studies have shown that

the presence of particular proteins is a useful indicator of cancer progression. For example, it is known that S100A4, a protein secreted by tumor cells, is a negative prognostic indicator for patients with melanoma, meaning it is linked to diminished patient survival. This protein stimulates angiogenesis, the development of new blood vessels; overexpression of this protein has been shown to lead to tumor growth and by extension lower patient survival.

marker is an indicator of the presence of melanoma, but it is not a good indicator of how the cancer would progress. Liu’s ongoing research involves looking for better markers for melanoma. Due to the severity of melanoma, early detection of the cancer is crucial to patient survival. Liu argues that the markers found in his research, when examined together, produced much more significant results than S100A4.

Like Saad’s research, Liu’s research may be translatable to a number of other cancers. He states, “We can utilize these markers to detect various types of cancer, not only melanoma but also colon, breast, etc.” Liu hopes that his research will lead to the discovery of significant markers for the detection of various cancers. He further states, “With our new marker we hope to generate much more significance, allowing earlier detection of cancer before [it] develops into later stages,” which could lead to better prognoses of patients diagnosed with melanoma or other life-threatening cancers.

The ongoing study began with blood samples collected from 205 Australian melanoma patients. The Ghosh lab found that a combination of variants of a certain protein had very significant results in predicting outcome of this cancer. These proteins inhibit the Wnt signaling pathway, which regulates development and cell differentiation. These results were verified through quantitative real-time polymerase chain reaction (qRT-PCR), a technique used to amplify and quantify a sample’s DNA, which is obtained from transcribing the available RNA via the reverse transcriptase enzyme. This technique is much more precise than traditional PCR since it takes measurements as the amplification occurs. It is a widely used, powerful technique today. The resulting data was used to generate Kaplan-Meier graphs, which statistically compare lifetime survival rates.

CELLULAR COMBINATION CAN CAUSE CANCER CHEMORESISTANCE

Cancer’s tendency to aggressively metastasize, or spread, is part of what makes it so life-threatening and difficult to treat. This behavior tells us that cancer cells are able to interact dynamically with our bodies’ immune systems and can develop ways of eluding it entirely. UC San Diego undergraduate Endi Santosa worked under Dr. Jack Bui, a clinical pathologist and director

Despite S100A4’s significance as a marker of the cancer’s presence, according to Liu, “[It] did not generate significance when predicting relapse and has less prognostic capabilities.” This

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of diagnostic immunology at UC San Diego, and has observed a novel cellular event highlighting cancer cell interactions with immune cells. This phenomenon increases chemoresistance, or the resistance of the cancerous cells to cancer treatments, and the probability of cancer relapse through an event known as cell-cell fusion: single-nucleus cells fuse with other cells to form multi-nucleate cells known as a syncytium (plural, syncytia).

Syncytia are common and can be observed in important normal developmental processes, such as muscle-cell differentiation and embryo development.

Santosa studied this phenomenon by culturing melanoma and fibrosarcoma cells with immune cells. He then observed that cancer cells were able to fuse with immune cells to enhance their own survival and ability to spread. This was visualized using a Crelox reporter system which involves Cre recombinase, an enzyme with DNA recombination abilities. This allowed the insertion of a fluorescent protein, tdTomato, in which the fluorescence of the protein upon exposure to UV light was evidence of a fusion event.

Cancerous cells can fuse with normal immune cells forming hybrid cells, or synctia. These multi-nucleated cells now contain mixed genetic information from both predecessors. They can then divide normally, perpetuating those mutant genes from the cancerous progenitor cell.

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By fusing with normal cells, tumor cells are able to increase their phenotypic and genotypic diversity. Using melanoma and fibrosarcoma cell models, Santosa has shown that cell-cell fusion not only promotes metastasis, but also contributes to chemoresistance and tumor evasion. He states that the “very scary� implication here is since these hybrid cells have adapted over time, evolving with these survival mechanisms, they could

potentially account for one possible avenue of resilient cancer recurrence. Thus, a good understanding of these hybridization mechanisms may lead to the development of effective countermeasures and successful therapeutics in the future.

brighter prognoses. Saad’s research sheds some light on said mechanisms. Exploration of miRNAs could possibly mean more effective predictive measures can be developed, leading to brighter prognoses for those diagnosed individuals. Saad states that, as far as the clinical implications of his team’s research goes, the data supports the idea that miRNAs are notable candidates for prognostic indicators.

TURNING TOWARD A TUMOR-FREE TOMORROW

Cancer and its avenues of progression are major points of discussion in today’s realm of biological research and medicine.

Santosa’s research shows the alarming possibilities of cancer relapse and chemoresistant cancer cells. Fortunately, research into these hybrid cells is burgeoning; there are still many approaches to explore, and Santosa’s studies can help open new strategies of chemotherapeutic treatment. Research into this mechanism of chemoresistance can elucidate ways to prevent cancer relapse, resulting in brighter prognoses for cancer patients.

All of this research is part of an ongoing effort to reach a common goal: understanding and eventually curing cancer. The past several decades, from approximately 1979 to 2011, have seen great strides in providing better prognoses for those diagnosed with cancer according to the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute; survival rates have been steadily increasing in the United States. This is all thanks to the research being done here at UC San Diego and at numerous other institutions. Saad describes the scientific community quite well when he says, “[in] science, we’re all standing on each other’s shoulders.”

Liu’s research has significant implications in the field of cancer detection. Melanoma is a severe form of cancer, but early detection can allow doctors to stop the disease from developing into later stages. The ability to translate these concepts of early detection to other cancers is a significant step in order to, as Liu states, “hopefully create ... much better biological marker[s] to [predict the outcome of] cancer[s].”

WRITTEN BY STEPHEN CALDERON AND KEVIN CHAU. Stephen is a Biochemistry and Cell Biology major graduating in 2016. Kevin is a Bioinformatics major graduating in 2017.

Understanding the mechanisms of cancer development is also crucial to developing treatments that ultimately lead to

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COAST to

COAST

By Rashi Saxena and Joyce Sunday Cover by April Damon and Illustrations

by Grace Lo

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uman life is built upon relationships, from relationships with other humans to those with the environment.

These diverse connections affect how we interact with and live in the world, similar to the integral relationships that are necessary to maintaining diverse species in ecosystems. An ecosystem includes all the biotic (living) and abiotic (nonliving) factors in a particular area. For example, the symbiotic relationships that plants develop are crucial to upholding the well-being of ecosystems. To carry out necessary life functions, plants depend on abiotic factors, such as carbon pools, and on biotic factors, such as soil microbes.

as rain, wind, temperature, altitude and soil. Such pools play an important part in the global carbon cycle and enable the exchange of carbon between the atmosphere and living organisms. In the past century, an increase in the amount of carbon dioxide released in the environment has caused an imbalance in the global carbon cycle, leading to climate changes including higher temperatures and lower precipitation levels.

Kirk Hutchinson, a second year General Biology major in Dr. Elsa Cleland’s lab at UC San Diego, conducted research to determine how these climate changes affect native and invasive plants. This project was carried out at the Santa Margarita Ecological Reserve, which housed equipment to perform extended, controlled rainfall experiments. To collect rainwater, researchers covered small plots of land with plastic and gathered the water in a storage tank. During this experiment, the researchers delivered different amounts of rainwater to plots of land. Some plots of the land were used as control groups, some only received half the amount of the average rainfall, and the rest got twice the average amount of rainfall. The plots were also separated into shrub-dominated and grass- dominated sections. Although the shrub seedlings of the control group got average amounts of rainfall, they still suffered a high death rate because the amount of water they received was not enough for their survival.

The student researcher came to the conclusion that lower

Without these links in ecosystems, life would not be sustainable.

A variety of factors, however, can alter these links. Carbon pools and microbes are affected by changing precipitation levels and the introduction of invasive plant species—species that are not native to a particular ecosystem. Researchers at UC San Diego have been conducting studies to determine the effects of these factors on plant life at the Scripps Coastal Reserve and the Santa Margarita Ecological Reserve.

EFFECTS OF PRECIPITATION ON CARBON POOLS AND THE ECOSYSTEM

Carbon pools are reservoirs of carbon that can accumulate or release carbon and are driven by abiotic components such

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rainfall amounts are harmful to the native shrub species. If precipitation levels continue to fall, the native shrub seedlings may not survive the changing conditions.

The carbon cycle is the process by which carbon is exchanged throughout the environment.

Carbon pools facilitate this exchange, driven by abiotic factors such as temperature, plants, and soil.

With changing precipitation patterns, exotic grasses are able to invade shrublands because of their ability to grow faster following a disturbance.

This allows them to quickly use up the surrounding available resources.

This hypothesis was further explored in another experiment conducted by Laurel Brigham, a third year Ecology, Behavior, and Evolution major in Dr. Cleland’s lab. Brigham studied how the soil carbon content is affected by the type of plant cover on the soil.

After plants die and become dead matter, they are broken down through biotic and abiotic processes. Biotic decomposition of dead matter heavily relies on microbes, and different plant materials have different rates at which

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they break down. When dead matter breaks down more easily, the carbon in the matter returns to the atmosphere more quickly, thus altering the size of the carbon pool in the soil. From this observation, Brigham postulated that the soil beneath the grass plots would have a lower carbon content than soil beneath shrub plots since shrubs might decompose slower than grasses.

She also hypothesized that northern UC reserves would have greater carbon content because of higher precipitation and greater plant mass entering the soil as dead plant matter.

to understand how the carbon cycle will affect climate change, we must study how different vegetation types impact carbon pool sizes.

HOW SOIL MICROBIOMES CONTRIBUTE TO THE ENVIRONMENT

Soil is known as one of the most diverse ecosystems on Earth; it consists of many interspecies interactions as well as inorganic matter. Many members of soil microbiomes have symbiotic relationships with plants. However, invasive plants can alter these relationships. Determining how invasive plants affect the soil microbiome can give us insight into the relationships between plants and microbial communities.

Research at UC San Diego in this field helps add to an ongoing microbiome project to better understand how microbial communities contribute to the ecosystem. The UC San Diego Microbiome and Microbial Sciences Initiative aims to research the role of microbes and how we can manipulate them to benefit the environment. As part of this project, undergraduate biology students in the lab class BILD 4 conducted original research and collected data to contribute to the on-going project. According to Dr. Stanley Lo, professor of BILD 4, the goal of this class is to understand how microbes function in the soil and contribute to the environment.

To test these hypotheses, Brigham conducted an experiment that was carried out along the coast at eight UC Natural Reserves, where soil samples were collected from plots of land dominated by either invasive grasses or native shrubs.

She collected 50 soil cores per reserve, totaling 400 soil cores.

The soil samples from each plot were analyzed to calculate the percentage of moisture content, and combustion was used to determine the organic carbon content.

Brigham found that the grass plots had lower soil carbon content than the shrub plots. As invasive grasses replace the native shrubs in the plant community, less carbon is stored in the soil. In turn, the amount of carbon dioxide in the atmosphere increases, significantly accelerating climate change. Soil carbon pools are the main components of terrestrial carbon pools and the global carbon cycle. In order

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Microbes play an important part in the ecosystem, developing many symbiotic relationships with plants. Researchers are focused on learning how these relationships work to understand how microbial communities affect our environment.

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Sophomore UC San Diego student Kshitij Gaur, along with a research group from the BILD 4 class, conducted experiments to investigate whether soil microbes associated with the native California sage or the invasive crystalline iceplant had significant functional and genetic differences.

Functional differences measure how an organism interacts with other organisms and the ecosystem while genetic differences show the presence of multiple species. The students conducted their research at Scripps Coastal Reserve, where they began by collecting soil samples during the fall and winter to account for differences in soil moisture. The group first tested the functional diversity of the soil using Biolog Ecoplate, a tool to analyze the stability of microbial communities.

The Ecoplate uses common carbon sources to test which sources the microbial communities use through a metabolic fingerprint that these communities leave. The changes in the

fingerprint pattern over time indicate the different way plants metabolized the carbon sources. To test for genetic diversity, the students isolated DNA directly from the soil, amplified the DNA sequences, and finally identified the specific species based on the samples. The test was used to measure evenness, referring to how abundant a particular species is compared to other species in the same area.

climate patterns, it has become even more important to study the relationships between plants and microbial communities in the soil to understand the effects on our environment. Due to climate change, Southern California has become drier, hotter and prone to more extreme precipitation events, such as this season’s El Niño. These changes have impacted the relationships between the plants, affecting how native and invasive plants survive in the changing climate. However, since invasive plants are not fully adapted to the new environment, their addition to the ecosystem can lead to problems such as improper water usage, increased amount of carbon dioxide in the atmosphere, and the extinction of the native plant species.

While much of this research is in its early stages, further studies will help scientists and researchers determine how changes in our climate will affect the species that form our ecosystem. Learning how relationships in the environment work will help us understand how to preserve the world we live in and foster the relationships of which we are a part.

In this experiment, the functional diversity test did not show significant differences, indicating a similarity in the carbon source utilization of both types of soil samples. However, the test for genetic diversity showed that many species in native plant soil had a higher evenness when compared to species in invasive plant soil, meaning that the California sage was able to survive better than the crystalline ice plant. According to Gaur, “At the natural reserve, invasive plants tended to die after raining as they were not utilizing water properly.”

These plants were not suited to the new environment and could not adapt while the native plants were able to survive.

However, continued study of these relationships is important to fully understand the effects to our environment.

WHAT THESE RELATIONSHIPS MEAN FOR US

WRITTEN BY RASHI SAXENA AND JOYCE SUNDAY. Rashi is a Bioinformatics major graduating in 2018. Joyce is a Biochemistry and Cell Biology major graduating in 2016.

Relationships between organisms in the environment are integral to maintaining many diverse species. With changing

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Losing Control: Afflictions of Mind and Movement

By Nicki Guivatchian and Rithvik Shankar Cover and Illustrations by Grace Lo

I

f there’s one thing that all humans share, it is the sense of freedom that comes with dancing like nobody’s watching.

Movement, dance, and rhythm are all parts of being fully alive; they are a universal language. The wide range of human motion is controlled by the complex and enigmatic nervous system. The tiniest error in wiring or a misfiring neuron can result in a devastating loss of motor abilities. Neurological conditions like Huntington’s Disease (HD) and epilepsy cripple movement and a person’s ability to live freely. Both of these conditions are puzzling to scientists and researchers at UC San Diego are working to learn more about these movement-impairing ailments.

may slow its progression. Lifestyles involving regular exercise that may also give patients better control over their movements for a longer period of time.

In the La Spada lab at the Sanford Consortium for Regenerative Medicine, researchers are on the verge of a potential breakthrough for HD therapeutics. Dr. Albert La Spada and his team, including UC San Diego undergraduate senior Martin Arreola, are evaluating pharmacological drug candidates for HD therapy by testing if the candidates cross the blood brain barrier and protect neurons from the mutant huntington protein. To do this, researchers did immunoblotting of brain tissues from HD mouse models. Immunoblotting is a technique used to analyze individual proteins in a protein mixture taken from cells. Arreola and various postdocs, including Dr. Audrey Dickey, treated mice genetically programmed to develop HD with KD3010, a promising drug candidate. This drug prevented the HD mice from developing motor problems and greatly extended their lifespans. Then, the researchers determined that the specific drug candidate did in fact lead to a dramatic reduction in toxic protein aggregation that is the cause of HD. KD3010 is a drug previously tested as a treatment for diabetes in humans, and found to be safe in a Phase 1 clinical trial. Right now, the lab is in the planning stage for a human Phase 2 clinical trial in HD patients, and Dr. La Spada hopes that these trials will be initiated in a year and a half to two years. “The approach we’re taking at the La Spada lab has the potential to help not only these

HUNTINGTON’S DISEASE

HD is an inherited condition in which nerve cells break down over time. The disease usually begins in one’s 30s or 40s and results in progressive physical, psychiatric, and cognitive symptoms. Since HD is an autosomal dominant disease, offspring who receive a mutated form of the huntington gene from a parent will develop the disease. The huntington gene (HTT) has the instructions to make the huntington protein, which plays an important role in nerve cells in the brain. A mutation in this HTT gene causes HD. As HD progresses, intellectual and motor tasks become increasingly difficult. Symptoms often include involuntary muscle movements and problems with coordination, impairing control over one’s body. Patients also experience paranoia, anxiety, and mood swings, affecting everyday interactions and relationships.

While there is no cure for HD, there are drugs being tested that

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Huntington’s Disease patients but also many other aging people predicted to develop related neurological diseases for which we have no cure or prevention,” said Arreola.

Another lab working on HD therapeutics, led by Dr. Jody CoreyBloom and Dr. Elizabeth Thomas with undergraduate Anthony de los Reyes, is testing a pharmaceutical drug called Copaxone (also

A mossy fiber tract is visible in the hippocampus of epileptic patients. Since these changes occur prior to seizures, Dr. Leutgeb’s lab believes that the memory impairments should occur prior to seizures as well, potentially making them a biomarker.

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known as glatiramer acetate) on mice with HD. HD is linked to deficiency in a growth factor called brain-derived neurotrophic factor (BDNF) in cells in the striatum in the forebrain, which is needed for neuron development, function, and survival.

Copaxone is used to treat multiple sclerosis, a disease in which the immune system breaks down the coverings of nerves, which distorts signals traveling to and from the brain. The team at the Bloom-Thomas lab believes that Copaxone could have a beneficial effect on patients with HD, as HD also involves the degeneration of neurons. The lab breeds mice that are designed to express part of the human HTT gene, and the observable progression of HD symptoms in these mice is similar to that in humans. After receiving the drug on a dosage schedule for a few weeks or months, the mice were put through a series of tests to measure motor control, like strength and ability to climb. Dr. Thomas reports that the lab has generally been successful in improving the movement of the mice.

is incapable of clearing them out. This is how the aggregates form. Dr. Bloom and Dr. Thomas believe that their drugs might be helping the UPS clear out more by increasing its activity.

With this information, it becomes easier to manufacture drugs targeted for helping the patient.

EPILEPSY

Another neurological condition that affects motor control is epilepsy, which is a disorder involving excessive and abnormal brain activity that can lead to seizures. The disorder develops from abnormalities in brain wiring and ion channels (rather than dying nerve cells, like in HD), imbalances in chemicals and neurotransmitters, and additional unknown factors. Symptoms occur mostly during seizures, when one experiences muscle twitches or spasms and the sensation of pins and needles. Like HD, epilepsy is not curable, but for many it is manageable as life between seizures proceeds with less severe interference on health and brain function. For some people, with proper medication, diet, devices, or surgery, epilepsy can be controlled.

Additional studies in the Thomas lab are trying to learn the mechanisms by which the drugs, such as Copaxone and histone deacetylase (HDAC) inhibitors, improve disease symptoms in HD mice. The researchers do this by taking out the mice’s brains, slicing them, and looking at protein aggregates. One hypothesis is that the product of the mutated HD gene gets misfolded after synthesis. If a protein is misfolded, it is usually cleared away by the ubiquitin proteasomal system (UPS). When a large number of proteins are misfolded, the UPS gets overloaded and

Dr. Jill Leutgeb and her lab, including UC San Diego undergraduate Mika Kamimura, hope to understand the functional impact of the anatomical changes that occur in the hippocampus, a small region in the temporal lobe of the brain. Specifically, they are interested in determining how circuit reorganization associated with epileptogenesis relates to seizure generation in epilepsy and associated memory dysfunction. Epileptogenesis is the period

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The temporal lobe contains structures critical for memory.

These structures are under investigation by the labs of Dr. Carrie McDonald and Dr. Jill Leutgeb for the role they play in epilepsy.

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during which seizures are developed as healthy brains begin to support seizure activities. The hippocampus and associated temporal lobe are essential brain regions for memory. Prior to experiencing spontaneous seizures, epileptics undergo structural changes in the dentate gyrus, a portion of the hippocampus that is responsible for encoding similar experiences as distinct memories.

These changes may result in some of the memory impairments associated with temporal lobe epilepsy. It is unknown when impairments associated with epilepsy first emerge. Dr. Leutgeb and her team hypothesize that because the alterations in the dentate gyrus happen prior to the appearance of seizures, the memory impairments would also precede seizures. To test this, rats are given kainate, a marine acid found in seaweed, to induce epilepsy. Rats are useful models for epilepsy as the changes in circuit organization are similar to those of patients. After given kainate, the rats are tested with behavioral pattern separation tasks during epileptogenesis. The study is currently ongoing and unpublished. However, if their hypothesis is correct, dentatedependent pattern separation tasks could be used as a marker of epileptogenesis. Pattern separation tasks are used to exercise memory in studies to determine whether one can accurately recall or recognize a stimulus. Failing these tasks would be an indicator of the memory impairments that accompany epilepsy.

Treatment could be started before the disorder becomes too severe, which would greatly benefit patients.

FREEDOM ON THE DISTANT HORIZON

In another lab, Dr. Carrie McDonald and UC San Diego undergraduate Richard Loi are studying the pathology of white matter degeneration in the temporal lobe. White matter is composed of myelinated axons of neurons. Temporal lobe epilepsy patients show degeneration in white matter tracts in the medial temporal lobe, a region critical for long term memory.

Dr. McDonald and her team examine maps of the whole brain using diffusion tensor imaging (DTI), which is used to detect microstructural changes. Loi is looking at advanced diffusion models in conjunction with traditional DTI. With standard diffusion measures, there are a lot of limitations, such as fibers crossing and other extracellular events that interfere with one’s ability to understand the underlying anatomy of the fiber tracts.

Loi is looking at an advanced diffusion model, called Restriction Spectrum Imaging (RSI), that may better explain pathology in epileptic patients by taking these different ways of imaging data and applying them to a normative group of patients. This way, the lab can distinguish true structural deviation from normal interpersonal variation. So far, he has found that by using RSI in conjunction with improved imaging registration techniques, one can show lateralized or lobe-specific patterns of white matter damage close to the seizure focus. Mapping these changes may benefit research in treatment for epilepsy.

The study is still ongoing, and Dr. McDonald says that the study requires a larger sample size to confirm these initial findings.

Very little is known about HD and epilepsy, so the research done at these UC San Diego labs are especially important for patients. By better understanding how epilepsy affects different brain regions, scientists can make better drugs that target and negate the effects it would have, making the condition more manageable. The drug testing on rats with HD helps researchers understand what is happening in the neurons of patients and contributes to the efforts to find a cure as well. Using the mice as models, researchers can develop drugs to help moderate the motor impairments that come with these life-changing conditions. There is still much to understand about these mysterious motor-impairing diseases, but continued research has great potential to help us give people their movement and freedom back.

WRITTEN BY NICKI GUIVATCHIAN AND RITHVIK SHANKAR. Nicki and Rithvik are Physiology and Neuroscience majors graduating in 2018.

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By Jaidev Bapat and Jordan Setayesh Cover by Youree Choi and Illustrations by Connie Mach

Model Science with Model Organisms

W

hile most people of this generation take the polio vaccine for granted, it might not have been made without first studying the polio virus in rhesus monkeys. In fact, many scientific breakthroughs would not have been possible without looking at model organisms, which are organisms that are studied to serve as a parallel to humans.

Important traits of model organisms include their small size and quick reproduction rates. For example, researchers often use the house mouse (Mus musculus), a murine (mouse) model, to study human diseases. Although not all diseases affect every organism the same way, many of the underlying biological mechanisms within model organisms can be applied to humans.

circulation efficiency is reduced, in relation to heart function.

Cardiomyopathy as a result of diabetes limits the heart’s ability to circulate blood throughout the body. Furthermore, it is thought that elevated blood glucose leads to changes in the muscle cells of the heart that leads to dysfunction, but the exact mechanisms are unclear. Cardiomyopathy is a multifactorial condition with various environmental and genetic factors, and one of these major environmental factors is diet. Nguyen’s experiment sought to explore the diet’s role in the development of this condition. In order to investigate the effects of diet alone, Nguyen studied the effects of long-term consumption of “westernized” diets filled with fats and sugars on the progression of cardiomyopathy in murine models.

Undergraduate students at UC San Diego utilize murine models to study arthritis and diabetes. While researchers acknowledge the limits of using mice as a model for human diseases, it is clear that, as was the case with the polio vaccine and rhesus monkeys, murine models have the potential to serve as important vehicles for scientific advancement.

The actual experiment involved feeding one group of mice with normal diets and another group of mice with diets containing a “Western” diet. Then, the experiment involved tracking the development of various structural and functional changes in the heart. The two different high-fat diets were differentiated by the amount of fat versus carbohydrate content. One diet contained 60% fat with 4% fat as a control, and the other diet contained 45% fat with 10% fat as a control. Nguyen utilized echocardiography technology to create ultrasound images of the heart and characterized the function of the heart. Two standard metrics used to quantify such efficiency are fractional (FS) and ejection fraction (ES).

FS is a measure of the shortening in diameter of the left

AT THE HEART OF MODEL ORGANISMS

In Professor of Anesthesiology Dr. Hemal Patel’s laboratory, UC San Diego undergraduate Alexander Nguyen studies diabetes-associated heart disease using mice. Many diabetesfocused cardiac studies have emphasized the importance of diabetic cardiomyopathy, a condition in which blood

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ventricle. ES measures the amount of blood that is pumped out of a filled ventricle with each heartbeat. Shifts in the heart’s function with diet alteration occur over a long period of time — Nguyen took these measurements every three months over a period of 18 months.

Nguyen’s results indicated that after six months, the mice on high-fat and high-sugar diets developed Type 2 Diabetes Mellitus (T2DM) and exhibited cardiac hypertrophy, an abnormal enlargement and thickening of the heart muscle. However, mice exposed to both high-fat and high-sugar content had statistically

Diabetic cardiomyopathy causes structural changes to the heart, decreasing the blood circulation efficiency. One of these changes, as illustrated above, is a decrease in the size of the left ventricular cavity. Due to having a smaller cavity, less blood can be pumped per beat, causing the decreased efficiency and a higher risk of heart failure.

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significant decreases in ES and FS in comparison to mice on just high-fat diets. This suggests that diet-induced obesity that results in T2DM leads to physiological changes in the heart, but higher sugar levels are necessary to amplify the severity of the heart’s dysfunction. However, after eight months, systolic blood pressure did not differ between normal and western diet mice, indicating that altered blood pressure may not be a factor in the development of cardiomyopathy. Overall, these findings support the idea that diet contributes significantly to cardiomyopathy.

More experiments are underway to examine the physiological changes going on within the T2DM murine model, but as Nguyen remarked, it is clear that “for both mice and man, our diets remain key in leading healthy lives.”

bind to cartilage and cause swelling. Dr. Corr and her students observed that the swelling peaked after seven days and decreased afterward in the resolution phase. During the resolution phase, only the female wild-type mice ceased experiencing pain.

The Corr Lab showed that such reactions could be due to the presence of TLR4 (Toll-like receptor 4) in male mice. Tolllike receptors are proteins that respond to certain bacterial components, but have also been shown to bind to molecules associated with autoinflammation (inflammation caused when the body’s immune system incorrectly responds to its own tissues). Wong’s research, which looked at receptor and signaling pathways in arthritic mice, showed that the TLR4 pathway regulates pain (by preventing pain from receding) in male mice, and is the main contribution to arthritis-related chronic pain in this case. Wong arrived at this conclusion by studying the relationship between TLR4 and MD2, a receptor that binds to TLR4. She induced arthritis in mice that lacked TLR4 and those that lacked MD2, and studied the sensation of pain in these mice. Wong used a technique known as Von Frey pain testing to study the pain sensation, in which mice feet were prodded with thin and thick nylon filaments. The mice that experience more pain will react to both thin and thick filaments, while the mice experiencing less pain will only react to the thicker filaments. The pain testing showed that the pain in TLR4-deficient mice subsided earlier than in MD2deficient mice and also that the absence of MD2 delayed the

MODELING ARTHRITIC PAIN

Arthritis is another human disease that is being studied using murine models. Dr. Maripat Corr is a Professor of Medicine at the Rheumatology, Allergy, and Immunology Division at UC San Diego’s School of Medicine. Under Dr. Corr, undergraduate students Stephanie Wong and Cody Ocheltree have used murine models to study pain caused by rheumatoid arthritis, an autoimmune disease. Individuals with this form of arthritis suffer from inflamed joints and continue to experience pain even after joint swelling is reduced.

In the studies conducted in Dr. Corr’s lab, arthritis was passively induced with K/BxN serum, which contains antibodies that

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sensation of pain. The exact mechanisms of why this is the case are not yet understood.

Ocheltree’s research also looked at the function of TLR4 pathways in arthritis. TLR4 is the only Toll-like receptor whose signals travel through two different signaling pathways. These two pathways are signaled through the MyD88 and TRIF proteins. To study these pathways, Ocheltree looked at mice that lacked different sections of the two pathways. Through Von Frey pain testing, Ocheltree found that the MyD88 pathway was responsible for early-stage pain sensations, and that the TRIF pathway was responsible for late-stage pain. Ocheltree hopes that this discovery will serve as a framework for future studies of pathways involved in both early and late-stage arthritic pain.

In Von Frey pain testing, mice feet were touched by thin and thick microfilaments. Mice that experience more pain are more sensitive, and will react to both the thick and thin filaments, while mice that are experiencing less pain are less sensitive, and will usually only react to thin filaments.

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Dr. Corr admits that there are many issues with using murine models. “Mechanical distribution is different in mice than in humans,” says Dr. Corr; mice walk on four legs while humans walk on two. Additionally, Wong acknowledges that mice don’t always cooperate with researchers. For example, during pain testing, mice will often struggle and move their feet when being touched by a microfilament to which they should not be reacting. Differences between how mice and humans move may be significant, because it is a joint disorder. Nevertheless, the conclusions gathered in Dr. Corr’s lab still have potential real-world applications. According to Ocheltree, the lab is “in collaboration with numerous other [labs at UC San Diego]

and these collaborations allow [Dr. Corr’s researchers] to work with people who are studying pain as well as laboratory drugs to target TLR4 and other TLR involved immunology in arthritis.” Already, Dr. Corr’s lab has explored the use of morphine derivatives (also known as binder) that interrupt TLR4 signaling. Because TLR4 is one of the receptors involved in arthritis pain, Dr. Corr hopes that these binders will help resolve this pain.

disease and use murine models to determine the mechanisms by which these causes occur. Thus, model organisms are powerful tools to study the effects of controlled manipulations.

While diabetes and arthritis are two diseases studied by UC San Diego researchers, the scope of the murine model spans much wider. Mice can be used to study any disease that occurs through a biological mechanism that is similar in both mice and humans; therefore, studying disease in mice is only half of the process.

Researchers must develop an understanding of how the disease in humans can be translated into murine model studies that will effectively elucidate the causes of the disease. Thus, the study of diseases using mice is a two part process. First, one must understand how the disease and its causes in humans correlate to that of mice. Secondly, mice can be utilized to systematically study that disease in depth. As we have seen, developing an understanding of how to model diseases in mice pays off by allowing researchers to take a perspective not possible in humans. Ultimately, mice serve as a different lens through which diseases can be studied, and perhaps this different perspective is all that is needed for the development of a cure.

WHERE MODEL ORGANISMS CAN TAKE US

Murine models allow researchers to study biological mechanisms associated with disease without the risk, complications, and ethical concerns associated with humans. Furthermore, using mice allows for the control of various aspects of the disease, such as the disabling of specific Toll-like receptors, making systematic studies of the disease possible. Such systematic studies allow the many facets of a disease, such as physiological, genetic, or environmental factors, to be studied in isolation so that causes, rather than correlations, of the disease can be deduced. Once a deep level of understanding of the biological causes of these diseases is achieved, cures can be developed.

Through the use of a murine model, UC San Diego researchers were able to study the role diet plays in the development of cardiomyopathy and the chronic pain associated with arthritis.

Both experiments sought to isolate one cause of a multifactorial

WRITTEN BY JAIDEV BAPAT AND JORDAN SETAYESH. Jaidev is a Molecular Biology major graduating in 2018. Jordan is a Physiology and Neuroscience major graduating in 2019.

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BIOLOGICAL SCIENCES STUDENT RESEARCH SHOWCASE 2015

POSTER WINNERS

CELL AND DEVELOPMENTAL BIOLOGY Alexander Nguyen

NEUROBIOLOGY Anael Rizzo

ECOLOGY, BEHAVIOR AND EVOLUTION Laurel Brigham

MASTER’S RESEARCH Tiffany Guan

GENETICS AND MOLECULAR BIOLOGY Scott Fassas IMMUNOLOGY, VIROLOGY AND CANCER BIOLOGY Maarouf Ahmad Saad

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ECOLOGY, BEHAVIOR AND EVOLUTION The Effects of Competing Species on the Timing of Germination and Fitness of Stipa pulchra

Justin Andrew Bain

Dr. Elsa Cleland

How Stereotyped is the Call of a Humpback Whale? An Investigation Using Acoustic Tags from Los Cabos, Mexico

Brooke Lynn Hawkins

Kerri Seger and Dr. Aaron Thode

Carbon Storage Along a Natural Precipitation Gradient Under Shrub and Grass-dominated Communities

Laurel Marie Brigham

Dr. Elsa Cleland

Interactive Effects of Altered Precipitation and Community Composition Regimes on Seedling Establishment in a Coastal Sage Scrub Ecosystem

Kirk Jackson Hutchinson

Dr. Elsa Cleland

Functional and Genetic Analysis of Soil Microbiomes of Native vs. Invasive Plants at Scripps Coastal Reserve

Kshitij Gaur

Dr. Stanley Lo

Effects of Altered Precipitation on Native and Exotic Biomass Production in a Coastal Sage Scrub Ecosystem

Tania Erandy Romero

Dr. Elsa Cleland

CELL AND DEVELOPMENTAL BIOLOGY Understanding the Role of Wnt9a Proteins in Hematpoiesis

Stephen Calderon

Dr. Karl Willert

Severity in the Progression of Cardiomyopathy Dependent on Dietary Content in a Murine Type 2 Diabetes Model

Alexander Dung Nguyen

Dr. Hemal H. Patel

The Role of MAP4K3 in Autophagy Induction

Xuan Yu Elian Lee

Dr. Albert La Spada

Plg-RKT has an Important Role in Mouse Mammary Gland Development

Alex Valenzuela

Dr. Nissi Varki

Role of Heparan Sulfate in Adipocyte Biology

Irene Sandley Lew

Dr. Jeffrey D. Esko

SIGNAL TRANSDUCTION H2O2 Wound Response in Mammalian Epithelial Cells

Deepika Suresh

Dr. Roy Wollman

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NEUROBIOLOGY Correlation Between the Severity of Several Neurodegenerative Diseases and the Levels of the Anti-aging Protein Klotho

Andrew Michael Arner

Dr. Robert Rissman Evaluating Huntington’s Disease Therapeutic Targets for Reduction of Toxic Huntington

Martin Arreola

Dr. Albert La Spada Computational Extraction of Cellular Signals from Mouse Spinal Cord Imaging Data

Nima Michael Assad

Dr. Axel Nimmerjahn Role of Reduced Protein Translation in Normal Neuronal Health and in Neurodegeneration

Angela Tung Chang

Dr. Albert La Spada Extreme Binocular Plasticity and Dynamic Strategy Implementation Sustains Visual Prey Capture in Cephalopod Cuttlefish

Victoria Cheung

Dr. Andrew D. Huberman

Individual Differences in Methamphetamine Self-administration Model Methamphetamine-addicted Phenotype and are Associated with Differential Cell Death in Dentate Gyrus of the Hippocampus

Avuveer Kaur Joea

Dr. Chitra Mandyam Blockage in Autophagic Induction as a Mechanism for ALS4 Disease Pathogenesis

Sarah E. Jordan

Dr. Albert La Spada Hippocampal Anatomical Changes Accompanying Memory Impairments in a Chronic Model of Temporal Lobe Epilepsy

Mika Kamimura

Dr. Jill Leutgeb LncRNA in Lithium Treatment of Type 1 Bipolar Disorder

Elizabeth Yuhjin Kim

Dr. Evan Snyder and Dr. Tannishtha Reya Profiling Epigenetic Alterations in Neurodegenerative Diseases: Histone Modification Alterations

Michelle Seowon Lee

Dr. Paula Desplats

Repurposing Glatiramer Acetate for Huntington’s Disease Therapeutics

Ab Anthony Mendoza De los Reyes

Dr. Jody Corey-Bloom and Dr. Elizabeth Thomas

A Drosophila Pheromone Circuit Described by an Incoherent Feed Forward Circuit Motif

Emily Pui Mun Leung

Dr. Jing Wang

Alpha-synuclein: Its Relation with the Alzheimer’s Disease

Wonjae Jang

Dr. Robert Rissman

Human Neural Stem Cell Grafts in Spinal Cord Injury: Integration and Maturation

Justine Jane Liang

Dr. Ephron Rosenzweig

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Visual Stimulation as a Strategy to Regenerate Retinal Ganglion Cell Axons After Injury

Brian Van Lien

Dr. Andrew Huberman

Phenotypical Characterization of iPSC-derived Neurons from Monozygotic Twins Discordant for Schizophrenia

Julien George Roth

Dr. Fred H. Gage

Charcot Marie Tooth Disease Type 2B: Study of a Mouse Knockin Model of Rab7V162M

Huayu Liu

Dr. Chengbiao Wu

Physiologic Soft Tissue Connections Affect Strain Distribution in Rat Sciatic Nerves

Jaemyoung Sung

Dr. Sameer Shah

Detecting Underlying White Matter Pathology in Temporal Lobe Epilepsy

Richard Qi Zhi Loi

Dr. Carrie McDonald

Repurposing Glatiramer Acetate for Huntington’s Disease Therapeutics

Brian Dat Tran

Dr. Jody Corey-Bloom

Screen for neurons involved in innate olfactory attraction behavior in Drosophila

Pavel Morales

Dr. Jing Wang

Changes in Hippocampal CRF Signaling Components with Alzheimer’s Disease Progression

Uyen Dao Vo

Dr. Robert A. Rissman

Profiling Of Npas4 Expression In the Hippocampus

Pouya Parsa

Dr. Brenda Bloodgood

Developing an in Vivo Disease Model to Study Fragile X Syndrome in Xenopus laevis Tadpoles

Tyler James Wishard

Dr. Hollis T. Cline

Delivery of a Constitutively Active Mutant Of The Netrin-1 Receptor, Deleted in Colorectal Cancer (DCC), to Promote Corticospinal Tract Regeneration Following Spinal Cord Injury

Anael Shaddai Rizzo

Dr. Mark Tuszynski

Identification of DNA Methylation Changes Associated with Inflammatory Genes During the Progression of Alzheimer’s Disease

Roxana Ellen Wishwell

Dr. Paula Desplats

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IMMUNOLOGY, VIROLOGY AND CANCER BIOLOGY Chromatin Immunoprecipitation of H3K27Me3 and H3k4Me3 in WT and Ezh2-/- Murine Neutrophil Progenitors During Differentiation

Syed Amaan Abidi

Dr. Rafael Bejar

Molecular Dissection of WNT Signaling in the PCSD New Series of Patient-derived Xenograft Models of Bone Metastatic Prostate Cancer

Theresa Jhoana Ramos Mendoza

Dr. Christina Jamieson

Enhancement of Potency of a TLR7 Ligand by Conjugation to Polysaccharides

Alast Ahmadiiveli

Dr. Dennis Carson

Ebola Prevention and Health Care Projects in Kpando, Ghana - A Cultural Perspective

Marlyn Moradian

Dr. Thomas Csordas

Investigation of EPCR Regulation of Dendritic Epidermal γδ T Cell Rounding

Darlene My Chi Diep

Dr. Wendy Havran

TLR4 Signaling Contributions to Arthritic Swelling and Pain in the K/BxN Mouse Model of Arthritis

Cody Leland Ocheltree

Dr. Maripat Corr

Survival Rate and Time of Death After Being Diagnosed with Medulloblastoma is Dependent on the Gene Amplification of MYCN, ALL3, and ODZ3 Genes.

Colby Warren Glazer

Dr. Sahoo Debashis

Alcohol-Dysregulated miR-30a and miR-934 in the Pathogenesis of Head and Neck Squamous Cell Carcinoma

Maarouf Ahmad Saad

Dr. Weg M. Ongkeko

Characterization of mTOR Pathway in Bladder Cancer

Goutam Krish

Dr. Donna Hansel Oncogenic Isoforms of the RON RTK Gene Are Constitutively Activated And Display Altered Signal Transduction Pathways

Raymond L. Lam

Dr. Andrew Lowy Nicotine Signaling in Caco-2 Cells to Define Biochemical Readouts

Ophelie Zoe Lavoie-Gagne

Dr. Brian Eliceiri

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Group A Streptococcus Survival in Macrophages Results in Cell Death and Inflammation

Jordan Steven Todd

Dr. Victor Nizet MD2 as a Regulator of Arthritis Pain in a Murine Model

Stephanie Yasue Wong

Dr. Maripat Corr Cell-Free DNA is an Endogenous Mediator in Inflammatory Arthritis

Joshua Young Cynming Yang

Dr. Maripat Corr

GENETICS AND MOLECULAR BIOLOGY Comparative Genomics of Mycobacteriophage Kersh

Teva Wu Bracha

Dr. Madeline Butler

Chemical Control of Gene Expression in Drosophila

Vaishali Talwar

Dr. Jing Wang

The Characterization of Human Specific Genes, CHRFAM7A and TBC1D3, in Myeloid Cells

Glory Thaonguyen Bui

Dr. Brian Eliceiri

Phage Hunting: A Survey of the Mycobacteriophages Isolated by UC San Diego Students

Elena Adrienne Westeinde

Dr. Madeline Butler

Isolation and characterization of ER-derived pre-peroxisomal vesicles

Scott Neil Fassas

Dr. Suresh Subramani

SIRT1 Gene Expression in Mouse Tail-Looping Models of Induced Disc Degeneration

Keianne Dale Yamada

Dr. Koichi Masuda

Studying the Structure-Function Relationship of Syndecan-1 in Hepatic Uptake of Remnant Lipoproteins in Mice Using Adeno-associated Viral 2/8 Vectors

Tiffany Lee

Dr. Jeffrey Esko

The Role of Varying RUNX1 3’UTR on RUNX1 Expression

Andrew Dy Yang

Dr. Dong-Er Zhang The Inhibitory Role of ISG15 in Antigen Presentation Pathway

Yue Zhang

Dr. Dong-Er Zhang

Predicting and Confirming Putative Functions of Genes in the Mycobacteriophage Kersh

Gregory Ryan Tadashi Lum

Dr. Madeline Butler

The Roles of the Cell Adhesion Molecule Cadm4 in Zebrafish Cardiac Outflow Tract Development

Chunsheng Zhou

Dr. Deborah Yelon

Isolation and Purification of Mycobacteriophage from Soil

Rachan Venkat Narala

Dr. Madeline Butler

SYSTEMS BIOLOGY Electron Microscopy of Human Urinary Exosomes in Diabetic Pregnancy

Ahish Chitneni

Dr. Satish P. Ramachandrarao

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BIOCHEMISTRY AND BIOPHYSICS Electrohypersensitivity: A Connection With Oxidative Stress

Nelish S. Ardeshna

Dr. Beatrice Golumb Microgravity During 30 Days Space Flight Induced Bone Morphological Changes and Bone Mineral Density Decrease in the Mouse Lumbar Spine

Kevin Cheng

Dr. Koichi Masuda

Structural Motifs of Sleepless That Facilitate Regulation of Nicotinic Acetylcholine Receptors

Clifford Zhuo Liu

Dr. William Joiner A New Marker in the Peripheral Blood of Patients Correlates with the Prognosis of Melanoma

Lawrence Liu

Dr. Pradipta Ghosh

MASTER’S ABSTRACTS Functional Characterization of the Tumor Suppressor RASSF2 in t(8;21) Acute Myeloid Leukemia

Elizabeth Tara Andrews

Dr. Dong-Er Zhang

Investigating a Role for DNA Damage Response in the Decline of Beta Cell Growth After Birth

Tiffany Kwok-Quew Guan

Dr. Maike Sander

Mechanisms of Ubiquitylation and ER-Associated Degradation of P23H Mutant Rhodopsin in Retinal Degeneration

Allen Chen

Dr. Jonathan Lin

Administration of Probiotics Normalizes Deficits in the Microbiota-gut-brain Axis Induced by DSS-colitis

Kevin Huynh

Dr. Melanie Gareau

Chronic Administration of Psychostimulants Reduces Hippocampal Neurogenesis in Young Adult Non Human Primates

Rahul Ryan Dutta

Dr. Chitra Mandyam

Vibrissae growth rates and foraging and migration patterns for juvenile male northern fur seals (Callorhinus ursinus) from St. Paul Island, Alaska using stable isotope analysis

Christina S. Kelleher

Dr. Carolyn Kurle

A New Axonal Splice Variant of HDGF-related Protein 3 Increases Mature Oligodendrocyte Numbers

Shereen Georges

Dr. Fred H. Gage

The Genetics of Language and Social Behavior in Autism

Mohammad Reza Khorsand

Dr. Karen Pierce

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Regulation of Cell Fate Specification in hESC-derived Pancreatic Cell Types

Dieter Ka Yeung Lam

Dr. Maike Sander

Abundance and Spatial Distribution of Juvenile Corals on Palmyra Atoll

Nicole Elizabeth Pedersen

Dr. Jennifer Smith

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