UTS Vol 8 (2017-2018)

Undergraduate Research Magazine with Proceedings of the Biological Sciences Student Research Showcase 2017

Volume 8 2017–2018

LETTER FROM

Hubris drives innovation, while humility facilitates remediation.

While great ideas drive accomplishments, for many of us accomplishments are not stumbled upon; on the contrary, they are built upon hundreds of failures. Our ability to grow from failure is what allows society to change, to live longer and tolerate societal development. Remediation, both objectively and subjectively, is what allows our world to change and revolutionize.

Science revolves around remediation not only as a field, but also as part of the scientific process. As researchers we must remedy issues and improve our methods. Much to our dismay, most experiments do not turn out the way they are intended. Not every gastrocnemius muscle withstands a fatigue inducing experiment, and sometimes results don’t yield a p-value less than 0.05. But not every experiment needs to yield positive results; science is grown from failures. We strive to remedy a solution and create better, more robust models from the data that we already have.

Similar to a thorough experimental procedure, the staff behind Under the Scope has gone through multiple trials to remedy and create a polished product. Our writers spend hours interviewing the brightest undergraduate researchers and drafting up brilliant pieces

highlighting top-of-the-line research at UC San Diego. Illustrators meticulously sketch out experiments while the production team crunches deadlines and harmonizes design and writing. All this hard work ultimately is torn apart by our editors, who provide insight to remedy mistakes and shortcomings. This common goal to improve is why we are able to present volume after volume of Under the Scope each year. From Alzheimer’s risk factors to dangerous microbes to even fatty livers, remediation is grounded in the principle of improvement from nothing. Whether it’s a failed experiment or a paragraph that does not flow, remediation is a central part of societal development and allows humanity to grow.

It is with great pride and pleasure that I present to you Under the Scope Vol 8. May each article inspire a passion to improve and a will to grow.

Madalyn DeViso Executive Editor, Under the Scope

EDITORIAL BOARD

HEAD ADVISORS

FACULTY ADVISORY BOARD

WRITERS

ILLUSTRATORS

Executive Editor Madalyn DeViso

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

Timothy Baker, Ph.D. James Cooke, Ph.D. Suckjoon Jun, Ph.D. Elvira Tour, Ph.D. James Wilhelm, Ph.D. Carolyn Kurle, Ph.D. Chih-ying Su, Ph.D.

Catherine Frusetta Michael Herron Michelle Pablo Daniel Fan Emma Huie Ayesha Mukhtar Peter Chew Ahsan Usmani Edward Abarado Ashni Vora

Qiuwan Liu Connie Mach April Damon Varsha Rajesh Vicky Hoznek

Features Editor Samreen Haque Production Editor Dominique Sy Features Design Editor Zarina Gallardo Head Technical Editor Jaidev Bapat Technical Editors Chinmay Kalluraya Alicia Ho Rebecca Hu Andrea Pedneault Jordan Raus

Manager, do/bio Center Hermila Torres

COVER ILLUSTRATION April Damon

TABLE OF CONTENTS ILLUSTRATION Varsha Rajesh

TABLE OF

18

contents

THE SYMPHONY OF HUMAN DEVELOPMENT Ashni Vora and Edward Abarado

THE 6 SOLVING PUZZLE OF

ALZHEIMER’S DISEASE Emma Huie and Ayesha Mukhtar

12 4 • Under the Scope • Vol 8

WHAT’S EATING YOU? Catherine Frusetta and Michael Herron

30

THE MISSION IS PRECISION Michelle Pablo and Daniel Fan

24

36

BIOLOGICAL SCIENCE STUDENT RESEARCH SHOWCASE 2017

MICROBES: THE UNSEEN LIFE ALL AROUND US

Peter Chew and Ahsan Usmani

sqonline.ucsd.edu •

5

SOLVING THE

puzzle of

ALZHEIMER’S DISEASE

t

here’s no sound more satisfying than the clattering of puzzle pieces being dumped onto a table. Whether it’s made of just four pieces or an intimidating one-thousand, somehow, each of the parts have to connect. Looking into the chaos of an unsolved jigsaw puzzle can be quite daunting. However, where some see a mess, others see a worthy challenge.

together the inside. In the same way, it is important to understand the frontiers of Alzheimer’s in order to know what to work with.

The current understanding of the disease is that it is an age-related illness, which has additional risk factors including genetics, head injury, heart health, and neuroinflammation.

FINDING THE EDGE PIECES

Here at UC San Diego, student researchers are at the forefront of the biological sciences, approaching a plethora of data and information as an opportunity to find truths, not unlike those seeking to complete a puzzle. A challenge that some have accepted is to study the nebulous Alzheimer’s disease (AD), a progressive form of dementia which affects memory, behavior, and thinking. As the sixth leading cause of death in the United States, Alzheimer’s looms over the lives of millions, and it is up to scientists and researchers to connect the puzzle pieces together to understand and hopefully cure this debilitating illness.

One prevalent theory is that AD is caused by plaques and tangles.

Plaques consist of protein fragments of beta-amyloids, which build up between nerve cells. Meanwhile, tangles are made of tau proteins, which twist and entwine within cells. An accumulation of plaques and tangles interferes with proper brain functions, eventually resulting in Alzheimer’s. The development of plaques and tangles can be predicted by genetics. Risk genes, like apolipoprotein E-ε4 (APOE-ε4), increase the chance of developing Alzheimer’s, while deterministic genes guarantee the development of the disease.

A common strategy to solve puzzles is to find the edge pieces, because filling out the border of the puzzle will ultimately help piece

One gene which has caught the attention of many researchers is the risk gene phospholipase D3 (PLD3). Genes which code for the

6 • Under the Scope • Vol 8

WRITTEN BY

Emma Huie and Ayesha Mukhtar

COVER AND ILLUSTRATIONS BY April Damon

enzyme family phospholipase D are essential for cell cytoplasm growth. PLD3 is generally expressed in neurons, but suppression of the gene causes a build-up of the beta-amyloid proteins found in plaques. Many scientists, including student researcher Armen Zeitjian, are beginning to understand the extent to which PLD3 affects neuroinflammation and the development of Alzheimer’s.

One way to understand the PLD3 gene is to find the extent to which PLD3 can be eliminated from neurons. In the Nemazee lab, Zeitjian genetically modified mice to suppress the PLD3 gene. He did this using the gene-editing technique CRISPR-Cas9, which essentially identifies, cuts, and pastes sections of DNA to create mutations.

Zeitjian used this technique to insert bases in mice DNA. This introduced a premature stop codon in the gene coding for PLD3, resulting in a high yield of neurons without the PLD3 enzyme.

Another way to study PLD3 is to see how its expression is linked to other cellular pathways. One of the many risk factors for Alzheimer’s is neuroinflammation. The interferon (IFN) pathway can mediate inflammatory responses such as the neuroinflammation associated with Alzheimer’s. Zeitjian studied the relationship between specifically the IFN-1 response and the PLD3 protein with a method called enzyme-linked immunosorbent assay (ELISA), which uses the color change of antibodies to identify and measure the amount of proteins in a sample. His findings showed that a binding of PLD3 proteins to DNA polymers may alter the IFN-1 response, triggering neuroinflammation. While more research still needs to be done, Zeitjian’s project helps to establish a greater understanding of the extent to which factors like PLD3 affect Alzheimer’s.

8 • Under the Scope • Vol 8

CONNECTING PARTS OF THE PUZZLE After making the border, many like to piece together individual sections of the puzzle and bring them all together at the end. By narrowing in on a particular part of the puzzle, it is easier to find connections and understand how things fit more clearly. Clarice Anne Resso, from Dr. Maho Niwa’s lab, does this by linking together the effects of stress in cells to age, and ultimately to Alzheimer’s.

Resso’s experiment focused on the endoplasmic reticulum (ER), an integral organelle which is responsible for the synthesis, modification, and transport of proteins in a cell. A cellular process that is heavily related to the ER is the unfolded protein response (UPR), which is initiated after an accumulation of misfolded proteins. The UPR will stop protein production, destroy the deformed proteins, and stimulate the production of molecules which aid in protein folding. If these steps are not executed, the UPR will prompt cell death.

By comparing two strains of yeast, Resso was able to observe the effects of stress and age on cell population growth. One of the strains (wild strain) was drawn from an ethanol rich environment, which is known to cause ER stress. The other was a common yeast lab strain. When exposed to stress, like the antibiotic tunicamycin, the wild strain had faster population growth over time compared to the lab strain. Genetic analysis shows several differences in key components of the UPR between the wild and lab strains; this could point to particular attributes which allow the wild strain to show such resilience in the presence of stress.

Resso conducted further tests by measuring the levels of a protein called inositol-requiring enzyme 1 (IRE1), which is essential to sensing ER stress. She found that over different phases of cell growth, the wild strain was able to produce more IRE1 and grow under stress compared to the lab strain.

One of her observations was that the production of IRE1 depended on the age of the cells; chronologically older cells were less able to produce IRE1 and could not respond to stress effectively. This key point can offer insight to age-related diseases like Alzheimer’s and connects the effects of age to molecular processes.

FILLING IN THE GAPS Another step to solving a puzzle is to take what is connected and fill in the gaps. Taking bits of what we know and forming a bigger picture adds definition to common knowledge. Undergraduate researcher Kristina Maria Lapira does this with her research, by studying the effects of mild traumatic brain injury (mTBI) and the APOE-ε4 risk gene on the development of Alzheimer’s.

Measuring levels of the protein Inositol-requiring enzyme 1 (IRE1) can give information about the age of the cell. Decreased levels of IRE1 are correlated with increased age of the cell, offering further insight on the relationship between molecular processes and age-dependent diseases, such as Alzheimer’s.

sqonline.ucsd.edu •

9

Cortical thickness is a measure used to determine the thickness of the cerebral cortex in mammals, and is commonly used when describing the effects of diseases affecting the brain. Lapira’s research uses this as a key measurement when determining the effects of mild traumatic brain injury (MTBI) and the APOE-ε4 risk gene on Alzheimer’s development.

10 • Under the Scope • Vol 8

In Dr. Lisa Delano-Wood’s lab, Lapira studied the combined effects of the apolipoprotein E-ε4 genotype and pulse pressure on cortical thickness in four regions of the brain associated with Alzheimer’s.

The goal of the research was to determine the relationship between higher vascular risk and APOE-ε4 presence being involved in cortical thinning in brain regions already vulnerable to Alzheimer’s in veterans with previous instances of mTBI. The subjects of Lapira and Delano-Wood’s study underwent magnetic resonance imaging (MRI) to examine brain activity, APOE-ε4 genotyping to determine the presence of the known risk factor alleles, and blood pressure assessment to measure vascular health. Delano-Wood and Lapira found that the presence of APOE-ε4 changed the relationship between cortical thickness and pulse pressure in the regions of interest. On one hand, the researchers found that subjects with lower pulse pressure and the presence of APOE-ε4 had cortical thinning in the four regions of the brain.

On the other hand, they found that participants who were missing the APOE-ε4 gene and had higher pulse pressure also had cortical thinning in the same regions of interest. They concluded that the combination of poor vascular health and increased genetic risk can lead to an impact on cortical thickness in regions of the brain known to be affected by Alzheimer’s.

This conclusion implies that Alzheimer’s is not a simple disease to treat, as it appears that higher pulse pressure may actually be helpful for those patients already dealing with higher genetic risk of

Alzheimer’s, while those without the genetic risk do not benefit from higher pulse pressure. Nonetheless, these experiments allow us to improve our understanding of the risk factors for the disease, thereby filling in some of the gaps of this puzzle.

FINISHING THE PUZZLE The pressure to discover prevention and treatment options for Alzheimer’s is greater than ever. The research completed on genetic and environmental risk factors such as brain injury, age, and presence of genes such as APOE-ε4 and PLD3 are all pieces of a puzzle that can lead to a potential cure and methods of prevention.

Researchers, once able to narrow down the scope of the disease with more certainty, can develop drugs that can target Alzheimer’s pathology and potentially treat patients with the debilitating disease.

These components of Alzheimer’s research may seem like individual puzzles in their own right, but they all connect to ultimately help scientists understand the larger puzzle of Alzheimer’s disease.

WRITTEN BY EMMA HUIE AND AYESHA MUKHTAR Emma is a Human Biology major graduating in 2020.

Ayesha is a Human Biology major graduating in 2018.

sqonline.ucsd.edu •

11

WHAT’S

e

eating YOU?

ntering college is a rite of passage. Many students are on their own for the first time and find themselves making a plethora of decisions for themselves. They can now choose to go out when they want, study whenever they please, and most importantly, eat whatever they can get their hands on.

It is difficult to have a balanced diet in a college environment. The term “freshman fifteen” is notorious across many college campuses for good reason. Eating right is especially difficult given the high availability of junk foods on campus, which, when coupled with the constant stress from the omnipresent midterm or final looming around the corner, is a recipe for disaster. Stress eating as a coping mechanism can be a huge temptation, and fatty foods such as pizza, chips, and donuts, are often the main perpetrators.

Consumption of a high fat diet over a prolonged period of time takes a toll on the endocrine system, especially the liver and its metabolic performance. The National Center for Health Statistics listed liver diseases such as liver cancer to be the ninth most common cause

12 • Under the Scope • Vol 8

of death amongst individuals in their 20s, which could suggest a higher risk of development for college-age students.

One type of liver disease closely linked to a high fat diet is nonalcoholic fatty liver disease, or NAFLD, which affects between 30–40 percent of adults in the United States. NAFLD is characterized by the buildup of fat within the liver and typically afflicts individuals who have been diagnosed with insulin resistance, type II diabetes, or high blood cholesterol levels—all of which are metabolic disorders that can develop from a high-fat diet.

There are four stages of NAFLD, with the first stage known as simple fatty liver. Simple fatty liver is the reversible stage of excess fat accumulation in the liver and does not cause permanent cell damage.

Without treatment, however, simple fatty liver leads to nonalcoholic steatohepatitis (NASH) which is the irreversible second stage, marked by inflammation and subsequent damage to liver cells. NASH can then progress to one of two outcomes: cirrhosis or hepatocellular carcinoma (HCC). Cirrhosis is the formation of irreversible fibrosis

WRITTEN BY

Catherine Frusetta and Michael Herron

COVER AND ILLUSTRATIONS BY Qiuwan Liu

scarring in the liver caused by repeated inflammation. This excess scar tissue strains the liver by reducing the blood supply of the hepatic portal vein from the liver to the heart. Cirrhosis of the liver is usually connected to the primary liver cancer, HCC, but the exact connection of the two is not well understood.

According to the National Institute of Health’s 2016 annual report, NAFLD is prevalent in 40–80 percent of people who have type 2 diabetes and in 30–90 percent of people who are obese. Thus, the primary treatment for NAFLD patients is to reverse simple fatty liver preventing simple fatty liver from progressing into NASH. However, UC San Diego students and faculty are methods to making NASH more reversible.

I. THERMOGENESIS: BAT Undergraduate student Norah Al-Azzam is one of these researchers.

She helped to conduct research on mucopolysaccharidoses (MPSIIIA), a disease that negatively affects fatty triglyceride levels in the plasma and liver, and causes a huge shift in energy metabolism that can lead to the wasting of the body in a condition known as cachexia.

MPSIIIA, a lysosomal storage disease, is caused by a deficiency of the enzyme sulfamidase. This enzyme normally breaks down sugar carbohydrates known as glycosaminoglycans in the lysosome. The lysosome is essential in the digestion of damaged organelles such as the mitochondria. However, without sulfamidase, the lysosome becomes impaired and unable to perform its usual function. This defect results in the accumulation of defective mitochondria in cells which manifests as the metabolic shift known as cachexia.

14 • Under the Scope • Vol 8

Brown adipose tissue (BAT) is specifically abundant in mitochondria, so the damaging of the organelles greatly affects the function of this tissue.

To investigate how MPSIIIA effects BAT, Al-Azzam utilized mice that cannot produce sulfamidase and studied the mitochondria and lipid droplets in their BAT. She used fluorescent antibodies designed to tag the failed mitochondria and found that there was a significant amount of damaged mitochondria in the BAT using the energy reserves of the body to generate excessive heat instead of ATP via thermogenesis. This leads to cachexia, or the wasting of one’s fat and muscle reserves.

However, there have been studies that suggest this may be reversible. Al-Azzam and her research team are currently testing the reversibility of MPSIIIA through enzyme replacement therapy, reintroducing the offending enzyme, sulfamidase, into the body.

This could potentially be useful in preventing elevated plasma triglyceride levels and therefore inflammation in the liver.

II. ENERGY HOMEOSTASIS: METABOLIC DISEASE AND INSULIN RESISTANCE Youngju Choi is another UC San Diego undergraduate researcher looking into urocotin 2, a corticotropin-releasing factor family neuropeptide that serves as a ligand for CRF type 2 receptors.

This enzyme plays a role in stress response and is currently used for clinical development for NAFLD-related conditions, such as congestive heart failure.

The ACOX1 gene is found in peroxisomes and encodes the enzyme peroxisomal straight-chain acyl-CoA oxidase, which breaks down very long-chain fatty acids. The ABCA1 gene encodes for ABCA1, which is an ABC transporter responsible for maintaining cellular cholesterol and phospholipid homeostasis. FABP1 encodes fatty acid-binding protein, frequently known as liver-type fatty acid-binding protein. This is because the protein is primarily expressed in the liver where it is involved in the binding, transport, and metabolism of long-chain fatty acids.

In the case of a deficiency of sulfamidase, the cell cannot dispose of mitochondria that are damaged by a heightened amount of triglycerides. The damaged mitochondria experience overactive energy expenditure in the BAT and ultimately lead to wasting syndrome.

Ras2 is a Saccharomyces cerevisiae gene encoding the guanine nucleotide-binding protein that undergoes activation in the presence of GTP when glucose is present in the environment. It affects growth regulation and one’s starvation response. ADRB3 encodes the beta adrenergic receptor ADRB3, which mediates catecholamineinduced activation of adenylate cyclase through the action of

sqonline.ucsd.edu •

15

G-coupled proteins. This receptor is located predominantly in the adipose tissue and is involved in the lipolysis and thermogenesis regulation.

The two arrays of 96 genes completed of the human insulin signaling pathway and human fatty liver were assessed for a twofold visual expression change to note its regulation. Thus, out of the myriad of genes upregulated and downregulated within either assay, only ABCA1 was upregulated in both the human fatty liver and human insulin signaling pathway arrays. Thus, ABCA1 may be useful in prevention of insulin resistance, as well as reversal of NAFLD. Therefore, urocortin-2 in relation to ABCA1 may be regulated in order to alleviate the onset of NAFLD.

III. DISEASE PROGRESSION: NASH, HCC Alleviation of cirrhosis symptoms, which eventually lead to NASH and HCC, may even be possible through the immune system.

Ingmar N. Bastian, a graduate student at UC San Diego, worked with mice and tested how their immune systems reacted to a high fat diet and its effect on the liver cirrhosis.

It is already known that drugs that inhibit the programed cell death-ligand 1 (PD-L1) can induce liver cancer regression, but Bastian specifically analyzed the roles of cytotoxic T cells, which attack cancerous cells, and immunoglobulin A (IgA), antibody cells that express PD-L1. Bastian notably used the MUP-uPA mouse model in this experiment due to the MUP-uPA mouse’s tendency to develop NASH from a high fat diet in a human-like manner. In

16 • Under the Scope • Vol 8

With the enzyme sulfamidase working properly, the lysosome is free to break down damaged mitochondria in brown adipose tissue (BAT), leading to a healthy liver metabolism.

NASH, IgA is often found to be accumulated in the liver, and with it comes an influx of PD-L1. It is suspected that the PD-L1 destroys the cytotoxic T cells, rendering them ineffective in the recognition of early onset cancer cells.

Bastian tested NASH development in MUP-uPA livers by knocking out IgA development in one trial and cytotoxic T cell development in another trial. Because cytotoxic T cells are responsible for identifying and destroying cancer cells, he found that the mice lacking these cells had greatly accelerated liver cancer development. On the other hand, the IgA-deficient mice were shown to decrease fibrosis, due to the lack of PD-L1 cells inhibiting the cytotoxic T cells.

Bastian’s experiments served to emulate the effect of the anti-PD-L1 drugs by knocking out their source, the IgA antibodies. Research such as this serves to create a greater understanding about the NASH and HCC as well as the general understanding of the functions of the liver.

CONCLUSION Fat build up in the liver is a worldwide problem that can often fester unbeknownst to the afflicted. This is why the research efforts by students such as Al-Azzam, Choi, and Bastian are so important. Both the greater general awareness of nonalcoholic fatty liver disease and the proposed solutions are vital to improving the quality of life for millions of individuals.

In fact, within the next couple decades, these ingenious treatments could come to fruition and significantly reduce the number of deaths related to the usually irreversible stages of liver disease, such as HCC and NASH. Whether the treatment is an enzyme supplement, a series of localized genes turned on or off, or the implementation of anti- PD-L1 drugs, research by students and faculty at UC San Diego will certainly play a role in its development.

WRITTEN BY CATHERINE FRUSETTA AND MICHAEL HERRON Catherine is a Biochemistry and Cell Biology major graduating in 2018. Michael is a Biochemistry and Cell Biology major graduating in 2018.

sqonline.ucsd.edu •

17

THE SYMPHONY

p

of human

DEVELOPMENT

icture the violins upfront, followed by the woodwinds, the harps, the French horns, the piano off to one side, and finally the percussion all the way in the back. The music begins slowly, increasing in complexity as it reaches a crescendo. You’re faced with what seems like a wall of sound, but if you listen closely, you can hear every instrument, every kind of different sound, timed to perfection to create one concerted symphony. A large orchestra can have between 20 to 50 different instruments, each one with its own unique sound. If all the members of an orchestra were to play all at once, they would lack synchrony and achieve nothing but a cacophony of sound, one that would barely qualify as “music.” What differentiates music from sound is its organization; every part of a song or a composition is well-timed and reads almost as if it were trying to paint a whole story.

Your body, in many ways, creates its own fantastic symphonies. The various proteins such as transcription factors, receptors and enzymes are its members, and the complex web of signaling pathways its compositions. In order to fully appreciate both an orchestra and the functioning of body at a molecular level, it is important to fully understand

18 • Under the Scope • Vol 8

each member of it and the role they play in the big picture. Only upon having this knowledge can one trace back to the mistakes that may be causing a composition to sound different or wrong. Similarly, to understand why our bodies may be suffering from a disease, one must identify and study the molecular players involved in that process.

THE CONDUCTOR A conductor in a symphony decides the pace, volume and instrumental balance of the symphony and is often the one to troubleshoot poor performances. In the same way, our body also has regulatory molecules which decide the paths of different proteins or products based on the needs of our body. These regulators are also needed as “checks” to ensure that a process has been completed successfully. If not, it recruits other molecules to either break down the faulty product or to fix it.

An example of one such regulator is heparan sulfate. Heparan sulfate is an important regulator of cell signaling pathways. It is responsible for controlling many of the processes that occur downstream in the

WRITTEN BY

Ashni Vora and Edward Abarado

COVER AND ILLUSTRATIONS BY Vicky Hoznek

Heparan sulfate is a regulator of many essential signaling pathways responsible for cell growth.

Researcher Erica Trinh found that in the absence of heparan sulfate, there was a significant increase in the rate of cell growth, suggesting that it acts as an antagonistic regulator of said pathways.

cell signaling pathway. Specifically, it is involved in the cell growth pathway. The absence of heparan sulfate can lead to excessive cell growth, which can cause problems within the body. Multiple hereditary exoteses (MHE) is a disease in which abnormal growth is observed in bones, eventually altering the shape and hampering their function. This case of a chaotic symphony producing “noise” that disrupts the structure and purposefulness of its composition, suggests that a key component is missing; the conductor appears to be on leave. Undergraduate researcher Erica Trinh working at the Esko lab chose to investigate the hypothesis that the regulatory molecule heparan sulfate was the missing conductor of our symphony. She hypothesized that in the absence of heparan sulfate, rapidly increasing cell growth was what caused the onset of MHE. To fully investigate the role of heparan sulfate in cell growth, she first created heparan sulfate-deficient mice and observed their wound repair phenotype. As wound repair is a process that requires cell growth, this allowed her to simulate the cell growth seen in MHE. She found that heparan sulfate-deficient mice did in fact have the ability to repair wounds faster than wild-type mice. This suggests that cell growth did occur faster in the absence of heparan sulfate,

20 • Under the Scope • Vol 8

thus further characterizing heparan sulfate as a key cell cycle regulator.

THE COMPOSITION A skilled orchestra can master several compositions over its career.

Different compositions have entirely different notes, tempos, and arrangements, and while the diversity of music is what attracts the crowds, each unique composition requires its own specific preparation and rehearsal process. A small fraction of our cells such as stem cells and other progenitor cells are also capable of this impressive diversity in function, but just like an orchestra, there is an extensive preparation period that precedes the diversification of a cell’s function. The process to differentiate stem cells or progenitors into more specialized cells requires a whole “crew” of molecules, which are specific to the specialized cell being made.

The immune system in our body frequently carries out cell differentiation in response to pathogens such as bacteria and viruses that may enter our bodies and cause disease. Akin to the pressure faced by an orchestra when performing a composition for the first time, our immune system also comes under the pressure to differentiate new cells to ward off invading pathogens. A chronic infection can stress the immune system and exhaust its crew’s ability to produce differentiated cells that can fight the infection. T-cells are one such type of cell that are produced specifically for the purpose of fighting off infection. During chronic infection, the immune system can exhaust its T-cells; this is suggested to happen due to the programmed death 1 protein (PD1). Like fatigued players that may be forced to quit the orchestra due to the physical and mental

stress, T-cells are thought to be forced to undergo cell death by PD1, under the stress of an infection. To avoid the death of these T-cells, one must regulate the protein PD1 first. Undergraduate researcher Clara Toma found that BRD4, a protein that alters gene expression by changing how DNA is unwound, may be the key to downregulating the function of PD1 and thus promoting T-cell differentiation during an infection.

THE MAINTENANCE A brand new, fine-tuned instrument is something to behold. Every stroke of the key, every contact with the hammer delivers a perfectly measured note. Our cells are like brand new instruments, precise in expression and tuned for efficient function. Once differentiated, somatic cells have pre-programmed routines that they perform as part of the symphony of development. Over time, repetitive usage wears the mechanisms of the cell, much like the wear-and-tear of instruments. Instruments gather dust, become out of tune, and lose timbre; notes become hollow, hammer strikes seem flat, and strings sound spent. Similarly, as the aging process wears cellular function, cell DNA accrues methylation. DNA methylation progressively silences the expression of multiple genes and allows only limited expression of genes. Eventually, essential genes also begin to perform incorrectly and recruit various enzymes to initiate apoptosis; the cell will continue to a programmed cell death, just as a musician retires an instrument.

However, undergraduate researcher Chan Nam Ao found that vitamin C treatment may be able to reverse this type of methylation. Chan found that vitamin C treatment of growing cells were able to increase

sqonline.ucsd.edu •

21

BRD4 is a protein domain involved in altering gene expression by modifying DNA histone interactions.

These interactions negatively impact the function of the PD1 receptor, preventing T-Cell apoptosis, and allowing for differentiation.

Note: This figure is based on tentative research and is largely hypothetical.

22 • Under the Scope • Vol 8

the expression of their target gene, gene X. Vitamin C regulates gene expression as an important cofactor for Ten-eleven (TET) 1 hydroxylase, an enzyme responsible for the DNA demethylation.

The vitamin C treatment decreased the aging phenotype of cells, increased proliferation rates, and reinvigorated gene expression.

Like an instrument finding its sound, treated cells reintroduced genetic components that had long been silenced.

CONCLUSION Bodily functions are elaborate compositions of protein harmonies, expressive genetic crescendos, and conducting proteins and substrates. The regulators mediating a variety of physiological pathways to optimize the perfect molecular harmony, control of cellular composition through the removal of infectious agents and mediation of cellular differentiation, the renewal of genetic instrumentation through the utilization of vitamin C treatments: all pieces of a grand bodily orchestra that continues the suspenseful piece called human development. The balanced performance does not last forever. Regardless of molecular conduction and pathway orchestration, the bodily harmony must compromise to continue function. Eventually, all orchestras come to an end. The only difference is that modern research is trying to get the body to prolong the symphony by finding novel ways for the instruments of the body to play one more beautiful arrangement.

WRITTEN BY ASHNI VORA AND EDWARD ABARADO Ashni is a Biochemistry and Cell Biology major graduating in 2019. Edward is a Microbiology major graduating in 2019.

sqonline.ucsd.edu •

23

MICROBES:

the unseen life

t

ALL AROUND US

hey might be invisible, but microbes are everywhere in our daily lives! Microbes can be found on every surface of our homes, in the soil we walk on, and inside our very own digestive tracts. There is little cause for fear, however, as a large majority of these microbes are relatively harmless and are an integral part of the ecological processes that support life on Earth.

For instance, microbes are essential in the recycling of energy and organic matter. Without such recycling, we would quickly find our ecosystem overloaded with dead biomass. This would not only be inconvenient and unsightly, but it would also be a death sentence for the ecosystem as increasing amounts of material and energy become trapped in waste. A similar relationship between us and microbes can be found at a much more intimate distance: in our guts, to be precise.

We human beings house a veritable garden of microorganisms in our stomachs. This symbiosis involves many digestive and metabolic benefits for humans, such as the ability to break down some forms of fiber and the ability to synthesize essential vitamins that human organs would not be able to produce by themselves.

Other times, microbial activity is less aligned with human interests.

24 • Under the Scope • Vol 8

Some microbes, known as pathogens, can cause infectious, and sometimes fatal, diseases in humans. However, medical researchers are continuously investigating new ways to combat pathogens. By understanding and then utilizing the mechanisms by which microbes function, researchers have turned those very processes to our advantage as well. Here at UC San Diego, students are helping lead the charge to further investigate microbes and ways to combat them.

MINING FOR MEDICINE Because of the microscopic world microbes inhabit, microbes must employ a variety of unique tactics in order to survive in their environment. One such technique is to saturate their surroundings with toxins to kill other microbes. Over the past century, humans have adopted a similar strategy by cultivating these very toxins, employing them in what are known as “antibiotic” drugs. These toxins are directed weapons that are often specific enough to disrupt the target microbes without harming other cells, which is a highly desirable characteristic in pharmaceuticals. However, because

WRITTEN BY

Peter Chew and Ahsan Usmani

COVER AND ILLUSTRATIONS BY Varsha Rajesh

E. Coli produces secondary metabolites that inhibit the growth of their microbe competition, making them useful for discovering new antibiotics.

these toxins are unable to kill all of the microbes they target, microbes have been rapidly evolving to adapt to current antibiotics. As such, antibiotic-resistant strains have emerged as a huge obstacle in medicine as they’ve rendered older antibiotics obsolete. The emergence of antibiotic-resistant strains have forced researchers to start anew and scour the world to develop new antibiotics. But with how widespread and diverse microbes are, sometimes the best place to find new antibiotic weapons is by looking at the seemingly mundane bacteria all around us. This is precisely what Ji Eun Shin of the Pogliano Lab at UC San Diego decided to do when searching for new Streptomyces strains that may yield effective, antibiotic compounds against bacteria that have developed defenses against current, widely-used antibiotic compounds. In fact, such novel strains can be found near the vicinity of the UC San Diego campus. Shin and her colleagues gathered over 40 different Streptomyces strains

26 • Under the Scope • Vol 8

by collecting soil samples from local areas throughout San Diego.

They proceeded to isolate the strains and test the effectiveness of the natural antibiotics that the Streptomyces strains produced against Escherichia coli and Bacillus strains in various growth media conditions. Shin found that some of those Streptomyces strains successfully inhibited the growth of their targets, presenting new possibilities for antibiotic treatments. But what Shin’s research truly highlights is not only the utility of microbes, but also that finding effective biological tools may be as simple as looking in one’s own backyard.

ILLUMINATING ANTIBIOTIC PATHWAYS The discovery of new antibiotics that humans can use against antibiotic-resistant bacteria is invaluable, but it is also important that scientists understand the mechanisms by which these antibiotics inactivate other bacteria. Undergraduate researcher Christine Peters of the Pogliano Lab investigates the mechanisms of action of various antibiotic compounds on bacteria. As previously mentioned, antibiotics target and disable only very specific vital systems in bacteria. By studying how antibiotics affect the bacterial cell, researchers can determine how to best use an existing antibiotic drug, or use this knowledge to develop new drugs that target a recently discovered mechanism of action. In order to facilitate the study and discovery of such mechanisms, Peters uses a method called bacterial cytological profiling (BCP), which uses fluorescence microscopy to examine how bacterial structures and pathways are affected by compounds suspected to have antibiotic properties.

Fluorescent dyes are used to stain structures of interest thus can

help identify how these compounds interact with bacteria. Using BCP, Peters screened the effects over 2000 compounds on E. coli.

Through BCP, Peters was able to determine which compounds lethally inhibited E. coli and how they worked mechanistically. As a result, Peters discovered that five compounds which previously weren’t being used in antibiotic research could be used to combat E. coli and S. aureus. Additionally, Peters was able to successfully identify three compounds with entirely unknown mechanisms that could effectively combat the bacteria B. subtilis. Thus, Peters highlights in her findings that BCP method is especially useful in the search for new weapons against recent, multi-antibiotic resistant strains. As such, the use of BCP presents a promising way to build an entire arsenal of potential new treatments against various strains of bacteria.

AMOEBA ABSENTIA Harmful bacteria, however, aren’t the only microbes we should be armed against. Take Naegleria fowleri, a particularly infamous protozoan that is better known as the “brain eating amoeba” for its ability to infect and damage the human victim’s central nervous system. Though infections are quite rare, N. fowleri infections pose a significant health risk with a fatality rate of 95 percent. Yet in spite of such a high fatality rate, little has been done in the way of developing potential treatment for N. fowleri. However, Goubin Fan at the Debnath Lab in the UC San Diego Skaggs School of Pharmacy proposes a new mechanism for the treatment of N. fowleri infections.

In his research, Fan outlines how RNA interference, a process that uses RNA molecules to suppress certain genes, can

sqonline.ucsd.edu •

27

Small fragments of RNA that are complementary to mRNA transcripts direct the destruction of said transcripts. This is useful as a defense mechanism against parasitic microbes.

inhibit N. fowleri’s ability to further infect and damage its host.

Specifically, Fan sought to target and inhibit the genes that produced DNA topoisomerase II, an enzyme which plays a crucial role in the replication of DNA. To accomplish this, Fan grew cultures of N. fowleri which he then mixed with 11 synthesized compounds that he was primarily investigating. To find compounds that could successfully inhibit topo II, Fan determined how much RNA each experimental culture could produce and compared the production of RNA to positive and negative controls. Through this method, Fan was able to find that six of the compounds were able to strongly inhibit topo II while the other five still managed to moderately inhibit topo II. In spite of these findings, Fan indicated that additional screening must be done in order to properly understand inhibitory mechanism of these compounds before a drug can truly be developed out of any of them. Even so, Fan hopes that his research can illuminate the role that topo inhibitors could play in the development of a better drug treatment for deadly N. fowleri infections. Moreover, Fan’s research further underscores how interference can be used to inhibit

28 • Under the Scope • Vol 8

the spread of other similarly infectious microbes by suppressing the genes that are crucial to their function.

MICROBIAL MECHANIZATION: LOOKING FORWARD Although microbes are instrumental in keeping both the planet and our own bodies going, we must remain wary of them. The staggering variety and adaptability of microbes, while beneficial to us, can at times be a danger as seen in drug resistant bacterial strains and N. fowleri. Microbes like these show us just how crafty microbial life can be. To that end, we need to find ways to be craftier by exploring new avenues of microbial research. By understanding the processes harmful microbes like N. fowleri use to propagate themselves, we can target those very processes and essentially shut them down with the right tools. By looking further, we can find ways to turn harmful microbes to our own side as we explore ways to develop new drugs and antibiotics. Ultimately, the constantly evolving nature of microbes presents a constant boon and struggle for us, one that we must both fight against and harness as we already have many times before.

WRITTEN BY PETER CHEW AND AHSAN USMANI Peter is a Molecular Biology major graduating in 2018.

Ahsan is a General Biology major graduating in 2020.

sqonline.ucsd.edu •

29

the mission

d

IS PRECISION

isease is a malicious entity that has always plagued humans. It causes great amounts of suffering, and as humans, we instinctively fight such a fate. We work to prevent these diseases and if that fails, we try to minimize the suffering and cure the disease. Disease treatment has progressed significantly over the ages, but many are still incurable and continue to torment humanity. As we and our treatments evolve, so do diseases, making every day a new challenge. In the face of these adversities, brilliant researchers are heroes in their own right; they work every day towards innovative treatments that exemplify precision, effectiveness, and beneficial results.

MICROBIAL MECHANIZATION LOOKING FORWARD OF V. CHOLERAE As antibiotic use increases, one challenge that researchers face is the growing number of resistant strains of bacteria. Normally, antibiotics target bacteria through certain characteristics that differ from human cells, such as having a cell wall. This antimicrobial method lacks specificity and precision as it often affects good bacteria too.

30 • Under the Scope • Vol 8

So what if we did not need antibiotics at all? Denny Bao, under the supervision of Dr. Soumita Das, explores one antibiotic free method to treat cholera, a disease of the small intestine. Cholera is a disease that causes diarrhea in patients, especially infants, and can often be fatal if not treated. The treatment routine for cholera is typically rehydration and antibiotics. However, the bacteria, Vibrio cholerae, causing this disease are building resistance to the usual treatments, rendering many antibiotics inert. Thus, Bao aims to treat the disease without subjecting the body to antibiotics. Instead, Bao wants to use a mixture of biology and technology: nanoparticles.

Nanotechnology shows great promise in disease treatment. Through Bao’s research, nanotechnology within the human body becomes a revolutionary method in battling cholera. Nanoparticles can be utilized to imitate the structure of the cells that V. cholerae typically infect. Imitating the target cells is a strategy used to trick the bacteria. It’s a basic decoy strategy in which the enemy’s attack is foiled by leading it to a trap disguised as its target. How does this work? First, the nanoparticles are engineered to be identical to specifically host cell receptors. Receptors can be thought of as a

WRITTEN BY Michelle Pablo and Daniel Fan

COVER AND ILLUSTRATIONS BY

Connie Mach

As toxins try to attach to target cell receptors, nanoparticles intervene using an enticing latch site that redirects the toxins. Once bound to the nanotechnology, the toxin is barred from affecting the cell, rendering it ineffective.

medium for cell communication; through them, instructions from outside the cell (extracellular messages), can be transmitted to the inside in order to produce a cellular response, such as triggering cell death. However, the receptors on host cells only allow specific things to latch onto them, a method called receptor specificity. This method ensures proper communication and cellular function. It is as if the cell has its own phone number, so the messenger must dial the correct number to share its message to the intended target.

Malicious bacteria are akin to spam callers in that they can obtain a host cell’s theoretical number, deceive it, and wreak havoc. However, nanoparticles turn the tables on the V. cholerae. Because the nanoparticles are imitations of target cell receptors, they attract the

32 • Under the Scope • Vol 8

bacteria away from the body’s natural cells.

The nanoparticles are engineered so they are not susceptible to infection, thus they can keep hold of the bacteria until destroyed by the host cell.

Bao’s research proved that the nanoparticles were able to neutralize the threat, inhibiting the toxins that cause diarrhea. Using nanoparticle decoys is more precise than antibiotics because they are engineered to target specific bacterial mechanisms rather than attacking general characteristics of bacteria. And, because Bao’s method uses host cell receptor specificity, resistance is not a major problem because the receptors do not mutate as often as bacteria.

Bao’s nanotechnological treatment may be unconventional, but that is what makes it a promising alternative to conventional antibiotics.

BINDING AFFINITY OF APY PEPTIDE INHIBITOR FOR ALS Though it is not infectious, amyotrophic lateral sclerosis (ALS), more commonly called Lou Gehrig’s disease, is another disease that presents many obstacles on the road to treatment. Because it is currently incurable, ALS is a prime example of how precision is imperative. If researchers could accurately narrow down the cause of the disease or the manner in which it develops, they would be one step closer to preventing or curing it. Lou Gehrig’s disease is like cutting the phone line between the brain and the body because the brain loses its ability to communicate with muscles, due to the death of neurons (the phone line). People diagnosed with ALS will experience a loss of muscle control; usually it is the voluntary muscles that are affected. These are the muscles that we consciously tell ourselves to use such as leg or arm muscles. As the loss of muscle control spreads, patients will eventually die because they will lose the ability to eat, swallow, and ultimately, breathe.

Since Lou Gehrig’s has proven extremely difficult to treat, undergraduate Jonathan Ly felt encouraged to search for a new way to approach it. Using biochemistry, Ly looked within the mechanisms of the cell. Cellular mechanisms explain the relationships between different cell parts and their functions. For example, neurons send and receive signals that are the extracellular messages meant to latch onto the targeted cell receptors. As previously discussed, the receptors are meant to regulate communication among cells to

assure proper behavior. Some receptors, however, can malfunction and improperly regulate the expression of a signal to be too little or too much; in this case, the receptor is not limiting the signal. Think of this overproduction in terms of a computer: when the electric signal becomes too intense and goes unchecked, the circuit board will short and the computer will not function. In ALS, researchers have discovered a problematic receptor called EphA4. This receptor is overactive and causes a “short” in the body’s circuitry.

In order to counter receptor overactivity, Ly looks to a specific protein. Proteins are crucial cellular components that play a role in cellular function and regulation. After studying the inhibitory ability of EphA4, Ly aimed to alter a protein that can regulate the receptor activity. The alteration is meant to help the protein latch onto the receptor with ease and follow its intended function. Narrowing down and focusing on the cause of the disease helps infiltrate and shut the system down before it destroys itself.

SMALL MOLECULE IDENTIFICATION OF P. FALCIPARUM Malaria, a well-known infectious disease, has also proven itself to be a worthy opponent for researchers. Malaria is common in extremely hot and humid environments, where mosquitoes make a home.

Millions of people are at risk of contracting malaria, and it causes hundreds of thousands of deaths each year. It is a highly prevalent disease that still eludes comprehensive treatment. While antimalarial

sqonline.ucsd.edu •

33

Cell signals travel throughout the body by diffusing across cellular junctions. Once the target cell receptors receive a signal, a cellular response is generated. To avoid neuron death, over signaling must be inhibited.

drugs do exist, genetic resistance to these drugs is on the rise. Thus, researchers must continuously innovate new ways to fight malaria.

Erika Sasaki, with the guidance of Dr. Elizabeth Winzeler, specifically selected for resistant strains of malaria to identify certain genotypes that may be responsible for higher resistance. In other words, the researchers searched for specific types of genes within the parasites that displayed a resistance to antimalarial treatments.

Resistance arises from certain genes that the pathogen “turns on” which decreases the effectiveness of the drug. Parasites and bacteria alike can produce certain macromolecules that inactivate drugs used to treat malaria, or can express a different set of proteins that

34 • Under the Scope • Vol 8

the medicine does not recognize. Regardless of the mechanism that confers immunity to the microbe, Sasaki deliberately treated the malaria parasites with such drugs to specifically search for those few strains that were not killed by conventional anti-malarial drugs.

The next step was then to identify what gene was responsible for the resistant strain, using the revolutionary technique CRISPR-Cas9.

CRISPR-Cas9 was recently developed in order to edit sequences of DNA with high precision using a mechanism that is found in bacterial cells. Therefore, if there is a suspected DNA sequence causing certain characteristics such as resistance, CRISPR-Cas9 can be used to edit the DNA to see if the gene is affected, much like turning a light switch on to see which light is connected to it.

The end result of the research identified several gene locations that were responsible for conferring resistance to malaria. Sasaki’s findings will prove integral for future biochemistry specialists and for pharmaceutical development. Through definite identification of what causes the resistant characteristics of the parasite, novel drugs with increased power can be created to fight the resistant strains.

SIGNIFICANCE OF NEW TREATMENT METHODS AND RESEARCH TECHNIQUES There is a constant arms race between evolving diseases and developing treatments. With newer advancements in biological techniques, technological barriers that once limited treatment options are gradually breaking down, allowing for innovative and more precise techniques to be explored and tested. Though all of the treatment methods discussed are still in their early stages, they all share one common theme: targeting a particular component of the disease. Whether it be taking advantage of natural specificity, the specific targeting of a protein, or accurately identifying genes propagating disease, all of these treatments are meticulous.

These experimental techniques truly revolutionize how we look at disease, showing that precision when exploring treatment is highly advantageous. As these methods become more refined, they will hopefully ripple throughout the scientific community promoting the notion that the mission is precision.

WRITTEN BY MICHELLE PABLO AND DANIEL FAN Michelle is a Human Biology major graduating in 2019.

Daniel is a Human Biology major graduating in 2020.

sqonline.ucsd.edu •

35

BIOLOGICAL SCIENCES STUDENT RESEARCH SHOWCASE 2017 BIOCHEMISTRY AND BIOPHYSICS ARYA DADHANIAARYA DADHANIA BIOLOGY EDUCATION KIMELTON JIM & JAKE SY

poster winners

IMMUNOLOGY, VIROLOGY AND CANCER BIOLOGY INGMAR BASTIAN NEUROBIOLOGY MANDY LAI & MARISSA JUSTEN

CELL AND DEVELOPMENTAL BIOLOGY CHRISTINE PETERS

SIGNAL TRANSDUCTION JORDAN SETAYESH

ECOLOGY, BEHAVIOR AND EVOLUTION CAROLINE IACUANIELLO

MASTER’S RESEARCH SAHAR ZARBAR

GENETICS AND MOLECULAR BIOLOGY LEAD: GAYATHRI KALLA

systems biology Loss Of Caveolin-1 Alters Cardiac Mitochondrial Function and Increases Susceptibility To Stress

RAVINA VERMA DR. HEMAL PATEL

36 • Under the Scope • Vol 8

Function of BAG3

PAUL SHICHAO ZHOU DR. JU CHEN

biochemistry and biophysics Molecular Mechanisms Regulating Scrunching in Dugesia Japonica

Missing Protein Node Prediction and Protein Quantitationin Bipartite Network Representations of Complex Proteomes

ARYA VINAYKANT DADHANIA DR. EVA-MARIA S. COLLINS

MIRANDA MONTGOMERY DR. JOHN YATES

Improving the Binding Affinity of the Apy Peptide Inhibitor for Future Treatment of Als

Site Directed Mutagenesis of Acp to Determine the Sequestration Location of a Pantetheine Analogue Probe, 4-Dmn

JONATHAN LY DR. PHILLIP E. DAWSON

MARY KATHRYN SWINTON DR. MICHAEL BURKART

Finding Novel Protein Structures in Chlamydomonas Reinhardtii in Order to Engineer Algae for Biofuels

Substrate Stabilization as a Means of Identifying Erad-M Retrotranslocation Suspects

MERYSSA MAILY TRAN DR. MICHAEL BURKART

DELLA SYAU DR. RANDOLPH HAMPTON

Conformational Changes in Tertiary and Quaternary Structure of Human Acetylcholinesterase Inhibited

by Paraoxon, Analyzed Computationally

Expression and Purification of Dimers of Recombinant Human Acetylcholinesterase and Computational Analysis of Dimerization Interface in Alpha/Beta-Hydrolase Fold Proteins

SAGAR MEHTA DR. ZORAN RADIĆ

NANCY CHAU DR. ZORAN RADIĆ

signal transduction Novel Mechanisms of Non-Coding Genomic Regulation Identified in Cardiac Disease-in-a-dish Models

Urocortin 2 Effects on Liver Metabolic Gene Expression in Mice with Insulin Resistance

DANIEL SING HAN CHEAH DR. ADAM ENGLER

The Role of Wnt-Fzd Specificity in Hematopoietic Stem Cell Development

JORDAN ALI SETAYESH DR. KARL WILLERT

YOUNGJU CHOI DR. MEI HUA GAO

Rare Protein Kinase C Variants in Alzheimer’s Disease

YIMIN YANG DR. ALEXANDRA C. NEWTON

sqonline.ucsd.edu •

37

neurobiology The Role of Astrocytes in Regulating Blood-Brain Barrier Properties in Response to Neural Activity

TAMARA CERA CHAN DR. RICHARD DANEMAN

Structural Differences Between MRGC Dendrites in on Sublamina vs. off Sublamina

BENJAMIN HENDY FINANDER DR. SATCHIDANANDA PANDA

Lower Nucleus Accumbens Volume is Associated with Reduced Reward-Based Decision Making in Veterans with History of Mild Traumatic Brain Injury

SAMREEN NEHA HAQUE DR. LISA DELANO-WOOD

5-HT2AR Agonists May Cause an Impairment in Probabilistic Reversal Learning in Mice

OMRON RAMZI HASSAN DR. SUSAN POWELL

Do the Acute Antipsychotic-Like Effects of Oxytocin Endure After Chronic Administration

BENJAMIN ELI KIAEI DR. DAVID FEIFEL

Development of a Noninvasive Blood-Based Molecular Test for Monitoring Disease Progression in Huntington’s Disease (HD)

AERI KIM DR. JODY COREY-BLOOM

Circadian Alterations Impact the Regulation of Insulin Degrading Enzyme in the Brain of Alzheimer’s Patients

TAEYEON KIM DR. PAULA DESPLATS

38 • Under the Scope • Vol 8

Characterization of Forelimb or Hindlimb Corticospinal Tract Regeneration into Neural Progenitor Cell Graft after Upper Cervical Spinal Cord Injury

DANIEL PETROVICH KULINICH DR. MARK TUSZYNSKI

Target-Specificity of Auditory Cortex Projections

MANDY LAI DR. JEFFRY ISAACSON

Apolipoprotein E-ε4 Genotype and Pulse Pressure Interact to Affect Cortical Thickness in Alzheimer’s Disease Vulnerable Regions in Veterans with Mild Traumatic Brain Injury

KRISTINA MARIA LAPIRA DR. LISA DELANO-WOOD

Neural Stem Cell Graft Differentiation and Interaction with Host Central Nervous System after Spinal Cord Injury

BRIAN VAN LIEN DR. MARK TUSZYNSKI

Evaluation of Neural Stem Cell Impacts on Pain Modulation Following Spinal Cord Injury

RANI SHIAO DR. MARK TUSZYNSKI

Investigation of Kisspeptin Neurons as Mediators of Stress Induced Disruption of Reproductive Function

CHRISTOPHER INJOON SONG DR. KELLIE BREEN CHURCH

Identification and Classification of Pacsin-1 as a Novel Ligand for Lrp1 in Schwann Cells

CURTIS GREGORY TRIEBSWETTER DR. WENDY M. CAMPANA

Evaluating Learned Behavior of Flies Using Aversive Operant Conditioning

EMILY CARMELA SERENO DR. RALPH GREENSPAN

Lipocalin-2, Energy Homeostasis, and HIV-Induced Neuronal Damage

ROHAN LOMESH SHAH DR. MARCUS KAUL

cell and developmental biology Natural Muscle Loss in the Lesser Egyptian Jerboa as a Model for Muscular Degeneration

Identifying the Mechanism of Action of New Antimicrobial Compounds Using Bacterial Cytological Profiling

JOEL MILAN ERBERICH DR. KIMBERLY COOPER

The Effects of Kappa-Opioid Stimulation Post-Cardiac Pressure Overload on Cardiac Function

MUGDHA ANIRUDDHA JOSHI DR. HEMAL PATEL

Interactions between the Basement Membrane Proteins PXN-2 and SPON-1 in C. Elegans Embryogenesis

CASSIDY CARINA LIU KOO DR. ANDREW CHISHOLM

Persistent Expression of Developmental Genes in Digits of Heparan Sulfate Deficient Mice: Proposed Mechanism for Multiple Hereditary Exotoses (Mhe) and Enhanced Regeneration

ERICA TRINH DR. JEFFREY D. ESKO

A Naturally Occurring Homeotic Transformation: Differential Hox10 Expression Causes a Vertebral Identity Shift in the Lesser Egyptian Jerboa

FAYTH HUI TAN DR. KIMBERLY COOPER

Discovery of Drugs Against Deadly Amoebic Encephalitis Caused

by Naegleria Fowleri

PATRICIA SHERRY OTO DR. RUBEN ABAGYAN

CHRISTINE ELISE PETERS DR. JOE POGLIANO

Identification and Validation of Small Molecule Targets in Plasmodium Falciparum

ERIKA ANNE SASAKI

DR. ELIZABETH WINZELER

Identification of the Targets of a GRAS Family Transcription Factor of Maize via Transposon Insertional Mutagenesis and Virus Induced Gene Silencing

ANH-DAO LE TONG DR. STEVE BRIGGS

Nanoparticle Decoys for Treatment of Infection with Vibrio Cholerae

DENNY BAO DR. SOUMITA DAS

The Effects of Human Milk Oligosaccharides on Parasitic Organisms

SHAMS A AL-AZZAM DR. LARS BODE

CRISPR/Cas9 Disection of Heparan Sulfate

JING LI DR. JEFFREY D. ESKO

Enhanced Wound Repair in Heparan Sulfate Biosynthetic Mutant Mice

LU LI DR. JEFFREY D. ESKO

sqonline.ucsd.edu •

39

genetics and molecular biology Genomic and Host Range Analysis of Novel Bacteriophage Dubu

RAVI KUMAR AGARWAL DR. JOE POGLIANO

Impaired Mitophagy in Sanfilippo A Mice Causes Hypertriglyceridemia and Brown Adipose Tissue Activation

NORAH AL-AZZAM DR. PHILIP GORDTS

CHAN NAM AO DR. KANG ZHANG

Effects of Methylation on Cell Aging by Vitamin C Treatment

Streptomyces Phage Isolation and Host Range

BENJAMIN GEENWA CHAN DR. MARCY ERB DR. JOE POGLIANO

Interrogation of the Cryptic Biosynthetic Gene Cluster IPF38-51 in Microcystis Aeruginosa PCC7806 Using Improved Genetic Tools and Methods

JIAYING CHEN DR. JAMES W GOLDEN

GUOBIN FAN DR. ANJAN DEBNATH

Targeting DNA Topoisomerase II—Developing New Drug Leads for the Treatment of Primary Amebic Meningoencephalitis

Using Genome Mining to Search Streptomyces Strains SFW and JS for Potential Antibiotic-Producing Gene Clusters

GAYATHRI A KALLA DR. MARCY ERB & DR. JOE POGLIANO

Impact of APOE on Heart Disease

VINEET TUMMALA DR. PHILIP GORDTS

40 • Under the Scope • Vol 8

Elucidating the Mechanism of KaiC Localization in Synechococcus Elongatus

BRIANA MARIE MCKNIGHT DR. SUSAN GOLDEN

New Interaction Between Galectin-3 and Cystinosis Reveals Mechanism of Kidney Pathogenesis in Cystinosis

ROY MILLER DR. STEPHANIE CHERQUI

Loss of Talin Protein from the Cardiac Myocyte Causes Early Onset Cardiomyopathy: Talin is Essential for the Structural Integrity of Costameres and Membrane Stability of Cardiomyocytes

EMILY MORENO DR. ROBERT ROSS

Phage Alvy: An Annotation and Analysis

EDWARD ALEXANDER MUALLEM DR. MARCY ERB & DR. JOE POGLIANO

Isolating Streptomyces and Producing Antibiotics

JI EUN SHIN DR. JOSEPH POGLIANO

Nuclear Factor of Activated T Cells (NFAT) and its Role in the Adult Drosophila Heart

SEAN J PAKNOOSH DR. ROLF BODMER

Does Age Affect the Unfolded Protein Response Signal Transduction Pathway?

CLARICE ANNE RESSO DR. MAHO NIWA

Age and Diabetes-Related Urogenital Muscle Atrophy and Fibrosis

SARAH CHI LOK TO DR. MAHADEVAN RAJASEKARAN

Employing CRISPR/Cas9 Screens to Synthesize Novel Therapeutic Treatments and Construct de novo Gene Interaction Networks Across Multiple Cancer Cell Lines

KYLE SALINAS SANCHEZ DR. JOHN PAUL SHEN

Identifying Novel Functions Of Rad53 And Mec1 In S. Cerevisiae that Mediate Replication Of Duplex Telomere DNA

WAVERLY TSENG DR. VICTORIA LUNDBLAD

biology education Understanding Students’ Knowledge Frameworks about Biology Research

KIMELTON MADRIGAL KIM DR. LISA MCDONNELL

Using Social Network Analysis to Examine Small-Group Interactions in an Academic Setting

JOSHUA PEI LE DR. STANLEY LO

Engagement With Biologist Guest Speakers in a Course-Based Undergraduate Research Experience Reduces Scientist Stereotypes Held by Students

AKSHITA TANEJA DR. STANLEY LO

ecology, behavior and evolution Effects of a Bee Pathogen, Nosema spp, and a Relatively New Systemic Pesticide, Flupyradifurone, on Honey Bees (Apis mellifera L.)

Molecular Methods for Exploring Diet And Microbial Ecology Within the Vast, Unknown, Twilight World of Mid-Water Fish

JOSEPH FRANCIS DI LIBERTO DR. JAMES NIEH

The Effects of Sivanto on Honeybees Sucrose Response Threshold and Learning

CORINA NOELLE GLOOR DR. JAMES NIEH

Zooplankton Community Structure Across an Elevational Gradient in Yosemite National Park

BROOKE LYNN HAWKINS DR. JON SHURIN

CAROLINE M IACUANIELLO DR. ERIC ALLEN

Photobiological Responses of a Common Coralto Natural Gradients of Light and Inorganic Nutrient Availability in the Southern Line Islands, Kiribati

ELLIS ANN JUHLIN DR. JENNIFER SMITH

Using the Tea Bag Index to Study Decomposition Within a Nutrient Addition Experiment

KARA LYNNE POWELL DR. ELSA CLELAND

sqonline.ucsd.edu •

41

immunology, virology and cancer biology Role Of Cytotoxic T Cells in the Development of Non-Alcoholic Steatohepatitis Related Fibrosis and Progression to Hepatocellular Carcinoma

INGMAR NIELS BASTIAN DR. MICHAEL KARIN & DR. SHABNAM SHALAPOUR

Irf7 is Essential for Collagen Induced Arthritis in Mice

ANTHONY MINH-TRI HUY BUI DR. MARIPAT CORR

Characterization of Imaging Changes in Brain Metastases Following Combination Therapy with Srs and Immune Checkpoint Blockade

ELENA JEAN SOJOURNER DR. DANIEL SIMPSON

The Non-Apoptotic Roles of Caspase-8 in Tumor Cell Malignancy

WILLIAM THIEN-TRI QUACH DR. DWAYNE STUPACK

Evaluation of IL-10 in an Animal Model of Rheumatoid Arthritis

Bromodomain-Containing Protein 4 (Brd4) Regulates Cd8+ T Cell Differentiation During Viral Infection

YUYA FUJITA DR. MARIPAT CORR

CLARA GORGES TOMA DR. ANANDA GOLDRATH

Chronic E-Cigarette Vapor Inhalation Induces Hepatic Fibrosis in Mice

Topical Therapy of IL-10 Using a Thermosensitive Drug Delivery Platform to Treat Murine Colitis

CHRISTIAN JASPER JAVIER DR. LAURA CROTTY ALEXANDER

The Orientation of Cer Shapes Kappa Light Chain Repertoire in B Cells

JIADAI MA DR. ANN FEENEY

The Role of Gene PLD3 in the Immune System

ARMEN HOVHANNES ZEITJIAN DR. DAVID NEMAZEE

Sex Differences in Toll-Like Receptor Regulation of Arthritic Pain in Mice

STEPHANIE YASUE WONG DR. MARIPAT CORR

42 • Under the Scope • Vol 8

ANIKA NAWAR ULLAH DR. AIDA HABTEZION AND DR. SIDHARTHA SINHA

P2XR and Caspase Deficiency Affect Arthritis in Males More Than Females

KEVIN YANG DR. MARIPAT CORR

Rna-Sequencing Reveals Hpv-Specific Dysregulation of Piwi-Interacting Rnas in Head and Neck Squamous Cell Carcinoma

YUANHAO QU DR. WEG M. ONGKEKO

master’s research Invasion Dynamics and Removal Strategies of Rhodactis Howesii at Palmyra Atoll

CORINNE GALIT AMIR DR. JENNIFER SMITH

Nuclear ABL Programs Extracellular Vesicles for Transmission of Ionizing Radiation-Induced Bystander Effects

JOSOLYN CHAN DR. JEAN Y. J. WANG

Molecular Mechanisms of ATF6 Mutations in Photoreceptor Diseases

PRISCILLA CHAN DR. JONATHAN LIN

Where, When, and Why Corals Grow, Shrink, and Die: Exploring Patterns and Natural Variations in the Spatial Distributions and Life History of the Scleratinian Coral Genus Pocillopora

SHO MICHAEL KODERA DR. STUART SANDIN

Dysfunctional Mitochondria May Promote Fatty Liver Disease and Tumorigenesis

KIRSTEN NICOLE MALO DR. GEN-SHENG FENG

Visualization of the Interaction Between Wnt9a and its Specific Fzd Receptors

Transduction of DRG Neurons Following Intrathecal Infusion of AAV9

Potential Role of Siglec-XII in Human Carcinomas

Microalgae as a Biotechnology Expression Platform: Visualization of Recombinant Protein Expression in the Microalga C. Reinhardtii with a Self-Cleaving Fmdv 2A Peptide

YUHSIANG CHENG DR. MARK TUSZYNSKI RAYMOND DO DR. NISSI VARKI

Insight into the Mechanism of Oximes Against Organophosphate Nerve Agents in Acetylcholinesterase

WILLIAM CHARLES HOU DR. PALMER TAYLOR

Conservation Applications of Stable Isotope Analysis: Can Pups Be Used as Proxies for Adult Females in Dietary Studies on Northern Fur Seals?

TANNER JAMES HOWARD DR. CAROLYN KURLE

Circulating Triglycerides and the Brain’s Reward Circuit

MOHAMMAD ALI SHENASA DR. THOMAS S. HNASKO

NICOLE QUYNH-THU NGUYEN DR. KARL WILLERT

EMILY NOELLE SCHMIDT DR. STEPHEN MAYFIELD

Effects of New Insecticide (Flupyradifurone) and Low Quality Sucrose on Honey Bee Flight and Mortality

LINDA TONG DR. JAMES NIEH

Type I Interferon Regulates Chemoresistance in Breast Cancer Cells

HRISHI VENKATESH DR. JACK BUI

PHLPP2 Negatively Regulates Phenylepherine (PE)-induced Cardiac Hypertrophy

SZU-TSEN YEH DR. NICOLE PURCELL

sqonline.ucsd.edu •

43

Under the Scope

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