The Beaker Spring 2016

the beaker Spring 2016

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Dear Readers, It’s here: the second issue of The Beaker for the 2015-2016 school year!

We are excited to share this edition before next year’s leadership team takes the reigns. Trust us when we say it will be in good hands!

Our issue features a wide variety of topics that we think you’ll love. A new invention allows users to create working circuits using a simple pen, an Italian professor claims to have performed the first head transplant, and lobotomies today pull from methods used in the mid-1900s. Hopefully one of those descriptions sparked your interest! Aside from the bizarre, we’ve included some more personal and serious topics, like threatening coral reef bleaching and the biochemical causes of depression. We hope that the following pages will inspire you to delve deeper and become as fascinated with the world of science as we are.

Because a majority of the writers and staff for this issue are current seniors here at Del Norte, we wanted to highlight a couple unique things you’ll find.

We’ve written about our original research from last summer and included a helpful perspective for students who revel in the humanities and may be a little unsure about pursuing a STEM career.

We hope you enjoy this installment of The Beaker. Cheers!

Singing Off, Gokul Swamy and Sona Trika

Visit us online at radix-education.org/beaker to read our previous issues. If you would like to give us feedback, join our team, sponsor, or advertise, contact us at beaker@radix-education.org.

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Contributors Editors in Chief ----------------------------------------------------------Gokul Swamy Sona Trika Content Editors ---------------------------------------------------------Ahana Chakraborty Flora Park Design Editors ----------------------------------------------------------Gokul Swamy Writers --------------------------------------------------------------------Gokul Swamy Sona Trika Flora Park Ahana Chakraborty Janelle Uy Zongyi Li Ivana Mai Abhi Nathan Revati Thatte Advisor --------------------------------------------------------------------Frank Liao

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Table of Contents Letter from the Editors ----------------------------------------------- 1 Contributors ------------------------------------------------------------ 2 Table of Contents ------------------------------------------------------ 3 Your Ad Here ----------------------------------------------------------- 4 Teen Depression ------------------------------------------------- 5 El Ni単o ------------------------------------------------------------ 7 ... And Coral Reef Bleaching? -------------------------------- 8 Circuit Scribe ---------------------------------------------------- 9 Monkey Head Transplant ------------------------------------ 10 The Lobotomist Today ----------------------------------------- 11 Why I Chose STEM --------------------------------------------- 12 Computerized Eyes --------------------------------------------- 13 Protein Kinases: ------------------------------------------------- 15 Citations ----------------------------------------------------------------- 17 3

Your Ad Here Interested in having an ad in the Beaker? Please email beaker@radix-education.org if you’d like to hear more about our rates and readership.

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Teen Depression

A look at one of humanity’s biggest plagues

By Ahana Chakraborty Depression. 20% of teens develop depression before they enter adulthood [4]. We have all heard of it. Some of us have experienced it. Not many of us know what is truly is. There are two causes of depression that have come to the forefront. The first is the scientific, biochemical cause the severe disorder, resulting from an imbalance in neurotransmitters. The second is the social pressure characteristic of teenage years.

There are three main neurotransmitters in our brain that are responsible for controlling our emotions: dopamine, noradrenaline, and serotonin. When an individual does or experiences something positive and the brain feels that the person deserves a reward, dopamine is fired through the neural synapses. These hormones promote general feelings of pleasure and calm. Drugs such as cocaine and acetaminophen can create effects similar to those produced by dopamine and are used to thus feel artificial ecstasy. Serotonin is responsible for mood and social behavior, appetite and digestion, sleep, memory, sexual desire and function. This neurotransmitter is in fact the cause of many depressive symptoms. The final key factor in depression is noradrenaline or norepinephrine. Noradrenaline creates what is known as the fightor-flight response and is also stress hormone. It provides people with a burst of energy [1].

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So how do these neurotransmitters play a role in depression? If these three factors are not balanced, the individual will no longer feel “happy.” When dopamine is in low supply, an individual is unable to feel pleasure, even in a positive situation. He or she may also have difficulty thinking.

Low serotonin levels can induce mood swings, aggression, and heavily suicidal thoughts. Suicide is the second leading cause of death in 15-24 year olds [5]. Finally, lack of noradrenaline reduces alertness.

People with depression are more vulnerable to bouts of extreme sadness and guilt. Other symptoms include complaints of physical pain (in lower back and head), fatigue, difficulty concentrating, anxiety, hunger loss or compulsive eating, substance abuse, and of course an obsession with death [3].

While depression can occur through genetics and an imbalance in neurotransmitters, teen depression is more often than not a social disorder. Expectations from society or from friends and family may cause a young teenager to feel unwanted and alone. Grades, sexual orientation, social status, or even bullying can transform once-jovial children into teenagers trying to end their lives. The first step in curing teen depression starts with the parent. Teenagers must be willing to speak with their parents, or a parent-like figure, about what is distressing them. Then the next step

If you or someone you know has depression or shows symptoms of suicidal thoughts, please call 1-(800)-273-8255 (National Suicide Prevention Hotline).

is diagnosis. Based on interviews and conversations with a psychologist, a teenager’s levels of depression and risk of suicide are determined. Lastly, the treatment.

The best treatment is a change in everyday habits. A healthier diet as well as appropriate amounts of exercise can increase levels of serotonin, which will in turn decrease the chance of suicidal thoughts. Talking to others and opening up also often helps to alleviate the stress of depression and allows the teenager to feel more comfortable in their skin. While antidepressants such as Effexor, Cymbalta, and Prozac are useful in such situations, they can cause a slight increase in suicidal thoughts. Therefore, it might be better to seek lifestyle changes rather than medication [3].

A person who has never felt true depression will never be able to exactly understand the fear and shame associated with the disorder. Individuals with depression are unable to put one foot in front of the other. Those affected have said that it feels as though a disease has crawled into one’s chest and made itself a home, plaguing every part of the body. Depression is essentially a black chasm into which one swirls as a result of environmental, internal, and biochemical neglect. It is exceedingly important to treat a depressed person with caution and care. Though you may not be able to understand exactly what he or she is going through, you must show your support no matter what, and you must let your friend or sibling, whomever suffers from this disorder, know that it is alright to feel what they feel. You just have to help them feel comfortable in their own skin. It only takes a few words of genuine encouragement.

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HAVE YOU MET “EL NIÑO”?

The weather pattern that changed our nation

By Ivana Mai El Niño and La Niña are the names given to the “complex weather patterns of the El Niño-Southern Oscillation (ENSO) cycle.”

Similar to many sibling pairs, El Niño and La Niña are opposites; El Niño refers to the warm phases of the ENSO climate pattern and La Niña refers to the cold phases. These patterns also trigger disruptions—unruly disturbances to “temperature, precipitation, and winds.” [2] The siblings live in the Equatorial Pacific, and reappear approximately every two to seven years. El Niño last surged in 2009, so it is no surprise that the weather system is back in play for the winter of 2015-2016. But who exactly is El Niño and how is he affecting us?

El Niño was discovered in the 1600s by fishermen off the coast of South America, who noticed uncharacteristically warm water in the Pacific Ocean. This can be simply explained as a complex series of climatic change, but more accurately refers to “the fluctuations in temperature between the ocean and atmosphere” [1]. The water cycle, taught to children in as early as elementary school, accounts for these fluctuations, which occur as part of the normal mechanics of evaporation, condensation, and precipitation. Clouds tend to form over warmer oceans, especially over the sun-drenched Equator. In usual situations, Pacific winds will carry the warm water west towards Indonesia and away from Central and South America. As this warm water departs, deeper cold water rises and prevent increased condensation. Little cloud formation yields little rain, which in turn creates drier weather for the Americas. El Niño arises when the Pacific winds are diverted or weakened. It is then heralded by the appearance of uncommonly warm, nutrientpoor water, leading to a period of warmer sea surface temperatures. The heated water along the West Coast of the Americas invites warm temperatures and accordingly, deeper rainfall.

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Although El Niño only occurs in the tropical Pacific region, the disturbances that it creates in the large-scale air movements bring about global consequences. In the United States, the weather will be hotter in the Northwest, drier in the Northeast, and wetter in the South. Globally, the Southern Hemisphere will be drier, affecting areas like Indonesia and northern South America. El Niño is often associated only with an increase in rain, but it rides upon Nature’s seesaw. The excess rainfall near the Equator is balanced by a decrease of rainfall in the Indian Monsoon. Thankfully, El Niño’s presence in California is of the “wetter and cooler” type.

However, this blessing of rain does not mean California’s infamous drought will disappear. The rain may “bring some relief” [3] to reservoirs and snowpacks as well as shocking floods and mudslides, but climatologist Dr. Patzert laments that El Niños are too irregular to put a dent in the drought: “Over a 25-year period, over the long term, El Niño provides only 7% of our water” [3]. El Niño is fierce, but also fast. Water conservation should not be put on the back burner just because some roads have become swimming pools. Therefore, El Niño must be treated like a very distant relative triple times removed—don’t count on seeing him soon.

CORAL REEF BLEACHING & EL NIÑO Is there a Dark Side to the Pop Science Term?

By Abhi Nathan

g?

In April 2014, researchers at the University n occur of Queensland analyzed “Porites” coral and corals colonies. Porites are known to be pretty ae), which resistant to environmental changes. The causes thescientists found that “there was a significant d turn white correlation between mass coral mortality events the and spikes in sea surface temperature over the he past 150 years.” The researchers began rine Science worrying about two things: the long-term susceptible effects of climate change and the short-term temperature effects of El Niño [2].

What heating What is El Niño? perature as The Earth Observatory at NASA explains y.” [3] that as a result of receiving more sunlight that any other part of the Earth, the Pacific Ocean s right tostores a lot of heat. The Pacific trade winds drag warm surface water towards the west, and colder water in the east rises to create the ute of s clear thermocline tilt. Thermocline is the depth of the o cycles ocean at which the rate of decrease of temperature with increase of depth is the connected.” een more largest. cause of the While the trade winds typically lose 2 build-up.strength in the spring, the Asian Monsoon usually replenishes them. tia is Sometimes, the trade winds don’t more m water isreplenish at all, however, and “the large central and eastern Pacific regions warm up (over a ers of of about 6 months) into an El Niño.” [1] it cannot period be t is

omfort in the will be reefs. The ool will d deeper, ffect outer ño’s off s that El ill decrease rrelevant [3].

What is Coral Bleaching?

Coral Bleaching can occur when water is too warm, and corals expel zooxanthellae (algae), which lives in their tissue. This causes the coral to lose all color and turn white [4]. In collaboration with the Australian Government, the Australian Institute of Marine Science writes, “Corals become susceptible to bleaching if the water temperature exceeds historical limits. What matters is the amount of heating rather than absolute temperature as this varies geographically.” [3] Were earlier researchers right to worry about El Niño?

The Australian Institute of Marine Science says “it is clear beyond doubt that El Niño cycles and mass bleaching are connected.”

For example, there has been more greenhouse warming because of the increased amount of CO2 build-up.

Additionally, thermal inertia is causing oceans to warm more slowly. Much of this warm water is settling in the surface layers of tropical oceans because it cannot be dispersed as quickly as it is accumulating.

But, we can take comfort in the fact that this connection will be temporary in most coral reefs. The Western Pacific Warm Pool will continue to get wider and deeper, making its central core affect outer reef regions during El Niño’s off years. The thermal peaks that El Niño currently delivers will decrease and eventually become irrelevant [3].

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Circuit Scribe

New invention combines imagination with circuitry

By Janelle Uy Have you ever wondered how common objects such as a refrigerator or an oven stay powered? The answer can be found in the concept of circuitry. A simple circuit needs a power source (typically a battery or electrical outlet), a conductive path which would allow for the movement of charges (typically made of wire), and resistor, which is any object that uses electricity to do work (refrigerator, computer, light bulb, etc.). Circuits are found in almost everything we use, and allow electricity to flow through and power these objects. For example, the wiring in a home is a very large scale circuit that delivers power to lights. Refrigerators are built with circuits that sense and control temperature. Ovens and stoves have circuits that transform electrical power into heat, sense the machine’s temperature, and allow users to select specific settings. The monitor screen I am currently looking at as I write this article consists of an incredibly complex circuit that is controlled by a computer system, which is an even more intricate circuit. All the circuits in these gadgets have one thing in common: wires. A new invention, Circuit Scribe, eliminates the hassle of wire and allows the user to create a circuit using pen and paper.

Creating a circuit is now as easy as counting “one, two, three.” Developed by S. Brett Walker and Analisa Russo, Circuit Scribe has revolutionized circuitry with a simple rollerball pen that writes in a conductive silver ink. The ink is created by placing an aqueous solution of silver nitrate into a flask of water combined with polyacrylic acid (PAA) and diethanolamine (DEA). The result is a smooth, non-toxic, conductible ink that does not smell

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and dries quickly; there is less time waiting for your circuit to dry and less chance of smudging your circuits [1]. How can we use Circuit Scribe? Simply grab one of these pens and a piece of paper (printer paper, construction paper, cardstock, etc.) and start doodling away.

Aside from the pen itself, there are also a variety of magnetic components that snap right into the circuit such as LEDs, buzzers, and buttons.

Now one can easily doodle their idea while simultaneously create a working circuit.

With a Circuit Scribe pen and MaKey MaKey (a device that turns everyday objects into touchpads) youtuber Jay Edry created his own self drawn pad in which he could control his own computer.[2] He drew and doodled in the different buttons and a mouse so that he could scroll and click, easily bring up his media center and internet, and control the volume of his computer. If someone could create this computer control pad using Circuit Scribe, the possibilities of what could be created in the future are endless. With a renewed focus on science, technology, engineering, and mathematics (STEM), teachers can use Circuit Scribe to give their students hands-on learning experiences inside of class and without the tedious use of breadboards (the surface on which circuits are generally made). Aside from this, circuits can also be easily drawn and cut as well as used alongside other electronic platforms. This invention will certainly transform the incorporation of circuitry into school curriculum. The potential and promises this invention brings are limitless due to the unique combination of circuitry and imagination.

Monkey Head Transplant

Frankenstein’s monster has come to life

By Zongyi Li Many of us have been to the Department of Motor Vehicles, infamously known as the DMV. We all know how it feels to wait in line for two hours, just watching people spend ages filling small paperwork jobs. Some of these papers, though, allow people to register to be an organ donor.

Currently, the list of donatable organs includes hearts, livers, kidneys, etc.

However, because of the work of one scientist, the entire head could become donatable as well.

Italian Professor Sergio Canavero, Director of the Turin Advanced Neuromodulation Group, claimed to have performed the first successful head transplant on a monkey. Canavero worked with a group of researchers at the Harbin Medical University in China to complete this operation. The head and body were stitched together and according to Professor Canavero, “The monkey fully survived the procedure without any neurological injury of whatever kind.” However, the spinal cords were not connected, leaving the monkey immobile. After twenty hours, the monkey was put to rest.

Following the success of the transplant, Canavero claimed to have a solution to connect the spinal cords of the body and transplanted head. He had already succeeded in performing this procedure on mice and hopes to move onto bigger test subjects; researchers in China have already conducted experiments on human cadavers. Canavero is optimistic that next year, he will be ready to perform a head transplant on a human being.

At this point, we expect Papa Franku to run out, carrying his gigantic clock, screaming “It’s time to stop.” And there are reasons for criticism. There is the ethical concern of individuality. How is a person defined? Is someone with the same head but a different body still the same person?

There is also the fear of how little is known about the results. Mary Shelly’s novel Frankenstein no longer seems to be a work of science fiction.

However, Canavero, unlike Frankenstein, has a purpose to his research.

His first human patient will be the 31-yearold Russian Valery Spriridonov. A new body would mean another chance at life for him, for he has a debilitating muscle deteriorating disease.

In the end, whether head transplants are a good or bad thing depends on how they are used. To quote author and journalist Lisa Ling, “There's so much grey to every story—nothing is so black and white”.

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The Lobotomist Today Has the Past come back to Haunnt us?

By Flora Park

Most modern psychologists agree that the mid 1900s was one of the darkest periods for mentally ill patients. In this era, one of the popular treatments for psychiatric conditions such as depression and attention deficit hyperactivity disorder was frontal lobotomy. This was a surgical procedure performed on the brain to destroy the neural connections of the frontal lobe to the rest of the cortex. A particularly gruesome method to alleviate the symptoms of some psychiatric disorders, frontal lobotomy often involved hammering through the skull of a patient with an ice pick in order to reach the frontal lobe—the main cognition center of the brain. it is no wonder that the lobotomy was declared “the worst idea on the mind” in history by the Royal Institution in 2006 [1]. However unethical this may seem, there is a similar procedure is still being performed on epileptic patients, but of course, in a more methodical and clinically safe way.

Lobotomy is widely used to combat seizures resistant to epilepsy medication.

Temporal lobe epilepsy is one of the most common forms of localization-related epilepsy, affecting approximately 60% of all epileptic patients [2]. It causes seizures of varying intensity, and is commonly associated with head trauma, loss of consciousness, neurological infections, childhood injuries, and even brain tumors [2].

Temporal lobe epilepsy is not easily treated by medication, so many individuals choose to undergo a temporal lobe resection, in which a section of the brain is removed from the temporal lobe to

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lessen the frequency of the seizures. In most cases of temporal lobe resection, the patient is anesthetized, the corresponding section of skull is removed, and the dura (a tough outer membrane of the brain) is pulled back to reveal the temporal lobe. The neurosurgeon then removes the specified part of the brain, and the patient is placed on the road to recovery. In some cases, however, the patient is anesthetized only to a “twilight state,” where he or she is conscious but sedated heavily. In this case, the surgeon can stimulate different parts of the patient’s brain with electrical probes while monitoring the patient’s responses and reactions in order to avoid removing vital sections of the lobes [3].

Temporal lobe resection has been proven to successfully eliminate or reduce the frequency of seizures in 60% to 90% of patients; usually, with a skilled neurosurgeon, vital areas of the brain are not harmed in the process [3]. Though the infamous “icepick lobotomy” is rarely practiced in the United States today, this does not mean that every type of lobotomy has been banned. Because of the horrors of mid 1900s lobotomic procedures, the whole idea of lobotomy, and even the word itself, is widely stigmatized in the modern world.

However, temporal lobe resection practiced in the medical field most often does quite the opposite of the “lobotomy” envisioned by the public—that is, improves the quality of life rather than ruining it.

Why I Choose STEM To Get it Right, You Gotta Get it Wrong

By Revati Thatte

I’m a humanities person at heart. English is my first love, and my favorite subjects to study have always been social sciences and languages. I had this fear of math—I could never quite put my finger on why that was, but it was a fear that always lingered in the back of my head.

Now that I think about it, I was always afraid of getting the answer wrong. Every time I slipped up on a timed multiplication test or mixed up my decimal places, that little jolt of terror would pass through my whole body. I’d feel ashamed of not scoring that perfect one hundred percent. It’s math! There’s only right or wrong, no in-between!

Math is the language of science, so by default I figured I would suck at biology, chemistry, and physics. Anything that had numbers-calculations, estimations, measurements—made my heart race in a panic.

What if I messed up an experiment? What if my data was horribly beyond the margin of error?

What if I got it wrong?

Turns out, science is actually all about getting it wrong. You have to get it wrong in order to get it right, you know? Trial and error.

It’s pretty much the foundation of all research.

You go into a project with an idea that you feel pretty confident about—a hypothesis—so you test it, but turns out it wasn’t what you expected at all. Good insight. Give it another go, but tweak it a little. You might get different results. Take note, and keep at it. It can be frustrating, but you learn loads just by getting things wrong.

Those experiments that we do in class are designed to help us master the material. If you

follow the instructions properly, you’re expected to get a certain result that reflects what you’ve been studying from a textbook. But making a mistake and getting different results doesn’t make you “wrong” at all. In fact, you’ll know what not to do. You’re always learning.

Quite possibly the best part about science is the creative component. You’ve got to be an inherently inventive person in order to start thinking about possible hypotheses to test or projects to start. Especially now, in the rapidly changing era of technology, being creative is a must. You’ve got to be able to see different ways of approaching the same problem, be able to cope with issues that quickly arise, and have the determination to see a project to its finish.

It took me years to figure that out, years of messing up chemistry labs and mixing up physics theories. I always thought science was for the math whizzes, the ones who could whip out mental math like lightning. I believed that you had to be perfect in the lab in order to be successful in the real world.

But once again, I got it wrong.

This fall, I’m going to be studying mechanical engineering. It’s a path I never would’ve thought I’d follow, but I’ve got this newfound appreciation for science and a higher confidence in my abilities to be successful in the engineering field. To my humanities people, it’s perfectly fine to chase after that English or history major, if that’s what you truly love to do.

But it’s not a bad idea to take a peek into a career in STEM; you might like it more than you think.

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Computerized Eyes Using Cameras to Assist with Physical Therapy

By Gokul Swamy

When most people hear the word Kinect, an image of limbs flailing in front of a television screen pops into their minds. Not so for Professor Pamela Cosman, Associate Dean of UCSD’s Jacobs School of Engineering. To her, the Xbox camera was a tool to help revolutionize physical therapy and perhaps even help wounded soldiers.

Last summer I assisted Dr. Cosman with some Kinect-related research at the University of California, San Diego Center for Wireless Communications. Normally when one breaks a bone or is otherwise severely injured, he or she is prescribed physical therapy to help regain mobility. The average person, however, cannot remember what angle is best for optimal recovery and is likely to perform exercises incorrectly without supervision. Not performing the movements per specification slows down recovery and can do more harm than good.

A few years back, Dr. Cosman and other scientists had the idea of using a pressure sensor to provide accurate feedback for movement to help people exercise correctly at home. The results were fantastic—with the feedback, the average person could perform by himself as well as he would with a therapist. Unfortunately, just to outfit one hand with pressure sensors would cost several thousand dollars, so the whole-body feedback necessary for the wide range of physical therapy exercises would be financially proscriptive for most.

A Kinect camera functions by bouncing particles off distant objects and using the time elapsed to calculate distance. Basically, the camera will tell users how far an object is. When you press on a deformable object, the object compresses and the depth of compression is positively correlated with the amount of force applied. Because a Kinect camera is both a regular and a depth camera, one could use the regular camera to track movement and the depth camera to measure force, enabling a complete physical therapy solution.

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Figure 1: We recorded pressure and depth measurements from two different sensors that started at different times. To align the curves, we used several methods including the Phase Shift method (pictured above) that was outlined by Dr. Cosman in a previous paper.

Figure 2: We then performed a linear regression on the alinged pressure and depth data. The slope of the line (.957) is very close to one and indicates a strong correlation between pressure and depth.

Enter our team. One of our first tasks was to isolate a hand from the rest of an image. We used an algorithm called the Convex Hull to do this. Imagine a wooden board with four nails driven into it so they form the corners of a square. If one were to take a rubber band and stretch it over the board and let go, a square would be formed. That’s the Convex Hull. We basically did the above procedure on a computer with each finger and the wrist counting as a nail (identified by their color contrast with the surrounding area).

Once we had the hand, we used a filter to eliminate any extraneous data points and then recorded the change in depth that accompanied a press at a certain force onto a stress ball. We were able to use this data to derive the relationship between force and compression for the test object and then set about creating a program that would use said equation to estimate force from depth.

We then designed an experiment to test our results. A test subject would come to our lab and we would tell him or her to push the stress ball until a bar on a computer screen hit a target.

The bar measured depth of compression. We then recorded the amount of pressure they applied versus time and used this to determine the average pressure applied. The result was compared to the expected pressure count to assess accuracy. Our goal was for users to receive the same quality of feedback from using our program that they would receive from a physical therapist.

Our experiment was recently approved by UCSD’s ethics board and we’re currently performing experimental trials. If our work is successful, we hope it will be used in UCSD’s medical school and other hospitals. Ideally, veterans who return with traumatic injuries could have quicker rehabilitation due to the software we created. Playing Halo as a soldier with a Kinect is pretty cool but taking care of our real troops certainly wins the prize.

Figure 3: Pictured here is one of our earlier attempts to isolate a hand from an image. We switched from the commerical software above into a convex-hull creating program designed by graduate student Keming Cao.

Figure 4: Our setup for our experimental trials was similar to the above. The subject is simultaneously recorded using both pressure and depth sensors while pressing on a deformable object like their arm.

Pictured above is Del Norte student Sayan Ray Chaudhuri who also assisted Dr. Cosman.

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Protein Kinases: Potential Drug Targets Further study of kinases like PKA and MSK1 may aid in counteracting disease

By Sona Trika

Last summer I learned that one of the best things you can do is become comfortable with being uncomfortable.

I’ve always loved my science classes, especially during the weeks when we got to experiment and complete lab reports. For me, there’s a kind of charm in being able to test theories and see them come to fruition at the lab table. But these theories are such that to some degree, you know that the outcome of an in-class experiment should reflect a certain result.

As I was looking for an interesting way to spend my summer last year, I kept that in mind. I knew that research was a great way to study the unexplored, but when I came across the BioChemCoRe program, I was a little intimidated. Doing biology and chemistry computational research required that I know or learn a couple of coding languages. I’d be coming in with cold feet while many of the other research interns were proficient with one or more language. I couldn’t pass up an opportunity like this though, and started on a research project I never would have thought I could complete.

My study, directed by Dr. Rommie Amaro and kindly facilitated by lab postdoctoral fellows and graduate student mentors, focused on two protein kinases.

Kinases are enzymes (substances that act as catalysts to bring about biochemical reactions) that make up about two percent of all human genes. They modify biological pathways by phosphorylating substrates. Disease occurs when phosphorylation goes awry. Studying protein kinases and their functions can lead to the development of drugs that can control cellular pathways.

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Figure 1: MSK1 is aligned [right] with ANP ligand [left].

Figure 2: PKA is aligned [right] with Azepane ligand [left].

Above are the two systems that I chose from the AGC family of the human kinome (kinase geome, or the collection of all human protein kinases). I wanted to compare their active site dynamics, and how flexible the proteins were. Flexibility helps the protein to adopt many conformations to do its job.

PKA proteins (Figure 1) are important since they are a simple regulatory protein involved in g-coupled receptor pathways. This means that they sense molecules from outside of the cell and activate inside signal transduction pathways. Specifically, PKA is involved in the cAMP (second messenger) dependent pathway—cAMP activates the kinase which then activates enzymes and regulates gene expression. MSK1 (Figure 2), on the other hand, responds to stress signals and can amplify transduction pathways this way. MSK1 is also important because it regulates the first step of gene transcription where DNA converts to RNA. I predicted that there would be more clusters in the active site (where the ligand binds to the protein for phosphorylation and chemical reactions) of MSK1. The more clusters a protein has, the more flexible it is. MSK1 might be more flexible because its job is more specialized and it is expected to be able to facilitate more movement to start the process of converting DNA to RNA. To use computational modeling strategies and complete the research, I soon learned the basics of coding in Python and working with software like Visual Molecular Dynamics. Using code and keystrokes, I added missing bonds and residues to my protein models. I felt like I was in a sci-fi film as I used the “spin” command to rotate the molecular conformations highlighted in rainbow colors. The research process was not without its challenges—since programs crashed and code failed regularly, I was always debugging and troubleshooting.

The results from the gromacs clustering (computer analysis) that I did

actually showed more clusters in the PKA, which was different from the original hypothesis. PKA’s greater flexibility as compared to that of MSK1’s is an interesting point for discussion. A guess to explain this would be that MSK1 needs to adopt a stable conformation in order to make sure that transcription occurs normally, but this requires further investigation.

I learned a great deal in these seven weeks, but it was more gratifying to see the practical implications of my study results. Because my results were unusual, I understood how important studying kinases could be. Scientists must understand how proteins function and move so that they can create drugs to effectively change the direction of the chemical reaction or cellular pathway that a protein is promoting.

This fall, I will be taking a couple of computer science courses, and I’m a little nervous since I’m still, relatively, a novice. But it’s time for me to dive into the deep end.

To learn more about my research, please visit: http://biochemcore.ucsd.edu/research/ and view the second to last poster on the page. You can also scan the QR Code below.

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