Spring 2012: Volume 4, Issue 2

The Amherst

ELEMENT Volume 4, Issue 2

Spring, 2012

Letter from the Editors We are excited to bring you the Spring 2012 issue of the Element! We would like to thank our writers and editors for working so hard to make the publication happen during this extremely hectic semester.

In this issue you will find our continuing efforts to make The Element a voice of the science community at Amherst. This semester’s faculty interview features Professor Patrick Williamson, professor of Biology whose unique view on life and passion for learning we have struggled to capture in our short two-page(+) interview. We also tried to show diverse aspects of writing a senior thesis through interviews with thesis writers this year. In addition to providing details of the theses, we were able to ask them about their personal experiences with working with their advisors, the biggest difficulty they had, and first-hand advice for future thesis writers.

We also feature stories of five students attending the Society for Neuroscience Annual Meeting at Washington D.C. last November.

They talk about their experiences of being amongst a crowd of outstanding neuroscientsts from around the world, and of seeing and hearing with their own eyes and ears where the neuroscience research is now.

This issue contains a number of articles investigating interesting everyday phenomena of the brain: food addiction (Food AddictionCould it Be? by Sunnii Roh ’15), dreams (Sweet Dreams- A Sugar Rush (of Sorts?) by Alexander Li ’14), forgetting (To Remember or not to Remember?

by Alice Li ’13), and hallucinations (Hallucinations are All in your Head: The Brain, that is by Sonum Dixit ’13).

Have fun reading!

Sincerely,

Haneui Bae

Sonum Dixit

About the Cover Photo The picture on the cover is a photomicrograph (photograph taken with a microscope) of a thin section of kyanite-eclogite from an ultrahighpressure terrane in the north Tibetan Plateau, viewed with both the analyzer and a gypsum plate in. The mineral at the very center is kyanite, an important aluminosilicate mineral. The kyanite grain is enveloped by a layer of both coarse-grained and fine-grained margarite (a silicate mineral made up of repeating “sheets”) + anorthite (the Ca variety of the mineral feldspar), as well as patches of cryptocrystalline corundum + anorthite.

The plate reveals how small many of the phases are in the outer layer (the blue and orange areas). In the top right is the mineral garnet with a rim of kelyphitic pargasite (an amphibole) and plagioclase (a feldspar). There is also a patch of zoisite (an epidote) in the top center right of the picture, and ilmenite to the top left (the dark patches).

I inferred that the different layers around kyanite represent different pseudomorphs, or replacement minerals, after reactions consumed most of the initial kyanite and zoisite, and used this series of reactions to create a theory of possible decompression at moderate temperature of the eclogite sample. The concentric nature of the minerals implies there is a potentially a time sequence of the replacements: kyanite first, replaced by margarite + anorthite, replaced by corundum + anorthite, etc. By calculating where these reactions theoretically occur in pressure-temperature space, I managed to create a P-T path through these reactions. This represents the changes in pressure-temperature conditions that the kyanite-eclogite sample experienced at some point in its metamorphic history.

The conclusion drawn from these mineral assemblages implies that the eclogite was brought to very high pressures but then subsequently decompressed at a high rate, such that the decompression is fairly isothermal. This may hold clues for the processes that exhume rocks from very deep, very high-pressure conditions. These rocks are particularly interesting because they have proven to use that continental subduction is possible, a process that Geo 11 students are taught just doesn’t happen.

Benjamin Lin ’12

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Table of Contents

The Amherst Element Staff Editors-in-Chief Haneui Bae Sonum Dixit Chief Layout Editor Jez Ng

Associate Copy Editors Tim Boateng Fan Feng Maile Hollinger Candice Kim Alexander Li Alice Li Maddie Lobrano Jez Ng Dan Rivera-Lanas Hyunsun (Sunnii) Roh Feature Contributors Fan Feng Nguyen Ha Alex Jaramillo Narendra Joshi Benjamin Lin Gabi Mateo Layout/Cartoon Aupola Kundu Alice Li

Get Involved!

Send questions, comments, letters, or submissions to theAmherstElement@ gmail.com.

Cover Feature 2 Complex Assemblage of Minerals in Cross Polarized Light

Benjamin Lin ’12

Features

18 2011 Society for Neuroscience Conference in Washington, D.C.

Haneui Bae ’13, Sonum Dixit ’13, Gabi Mateo ’13, Alexis Jaramillo ’12 and

Narendra Joshi ’13, 31 Medical School or Graduate School? (Sophie Kim ’12, Mable Lam ’12 and Akosua

Korboe ’12)

Fan Feng ’13 34 Interview with Professor Patrick Williamson

Nguyen Ha ’13

Letters

4 Food Addiction, Could It Be?

Hyunsun (Sunnii) Roh ’15 8 Sweet Dreams, A Sugar Rush (of Sorts?)

Alexander Li ’14 12 Hallucinations are All in your Head: The Brain, that is

Sonum Dixit ’13 14 DNA Double Strand Breaks and How Life Combats Them

Maile Hollinger ’15 22 Demystifying the Electric Car

Sam Ubersax ’15 28 To Remember or Not to Remember

Alice Li ’13

Thesis Interviews

6 Yeast Model of Notch Signaling Pathway (Nina Yoo ’12)

Sooji Choi ’14 7 Polarized Petrographic Microscopes and Study of Rocks

Benjamin Lin ’12 10 Clozapine’s Effects on Rat Anxiety in the Clozapine Induced-Schizophrenia Model

(Brigit High ’12)

Dan Rivera-Lanas ’14 17 Engineering Small Molecule Sensitivity into the WPD Loop of Shp2 (Chris Lim ’12)

Kate Savage ’12 20 Mining for Wildfire Geochemistry (Sarah Beganskas ’12)

Tim Boateng ’13 25 Stock Volatilities: Long Memory and Common Factors (Dang Trinh ’12)

Tianshen Rong ’15 26 TMEM16F in Activated Ca2+-activated Phospholipid Scrambling (Nate Belkin ’12)

Kate Savage ’12

The opinions and ideas expressed in the Element are those of the individual writers and do not necessarily reflect the views of the Element or Amherst College. The editorials are a product of the opinions of the current editors-in-chief of the Element. The Element does not discriminate on the basis of gender, race, ethnicity, sexual orientation, scientific background, age, or hair color.

Research findings published in the Element are not intended for wide distribution or for the reader’s profit. As a member of the Amherst community, please use the information and data presented in the Element judiciously.

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Letters

Food Addiction... Could it be?

Hyunsun (Sunnii) Roh ’15

Food is a subject that never fails to enter our daily conver- lives clearly show how the addiction criteria apply to food. sations. Whether it is that new yummy brownie recipe, the new Further criteria for addiction include tolerance, the need tea place that just opened in the next town over, or the raspberry for markedly increased amounts of the substance to achieve inbars that will be at Val for dessert, we constantly think about toxication2, and withdrawal, the cessation of use or provision of food. When the term ‘food addict’ first came to being, it was a drug, resulting in cravings and abnormal bodily function due to mostly used as a colloquial term. However, with clinical studies physical dependence on the substance.5 Cigarette smokers demshowing a very likely connection between high-sugar, high-fat onstrate increasing tolerance very clearly, with their transition into foods, and obesity, via the link of addiction, this term may have chain smokers, and withdrawal, with their difficulties with quitting resounding social implications in a world with over 600 milsmoking. Tolerance also develops for food addiction. Sugar acts lion obese individuals.1 With ‘food addiction’ as a reality, eating as an analgesic very early in life, which means that just as taking healthily becomes the responsibility of not just the person who painkillers reduces stomachaches, eating chocolate would have the indulges in addictive foods, but the responsibility of our society same effect. Unfortunately, tolerance to the analgesic effects of as well. sugar develops around 18 months of age.2 Although many people According to the Fourth Edition of the Diagnostic still do turn to high-sugar foods at times of stress or emotional and Statistical Manual (DSM-IV-TR) which provides common turmoil (like during a hell-week), the sugar does not actually allanguage and criteria for classifying mental disorders, seven leviate any physical pains for adults. This analgesic tolerance is specific criteria characterize an ‘addiction’, all of which apply to also observed in opioids, substances that form painkillers, which food addiction to varying further supports the idea degrees. Two criteria are that food addiction is a (1) persistent desire or diagnosable problem. Inunsuccessful efforts to cut creasing tolerance is also down or control substance evident in patients with use, and (2) continuous bulimia nervosa, as their substance abuse with food binges occur more the knowledge that it is often with larger portions causing or exacerbating of food as the duration physical or psychological of the illness increases.2 2 problems. If food were

Along with obsernot addictive, a weight vations in clinical studies, loss industry that amasses there are biological billions of dollars every explanations for food adyear in profits3 would not diction. Imaging studies be feasible. Furthermore, have shown that specific despite the now wideareas of the brain are spread knowledge of the activated by both drugs benefits of healthy food, and food7, and it follows the existence of groups that over-consumption such as ‘Food Addicts in of food likely involves Recovery Anonymous’4 dopamine and reward suggests it is not easy to centers in the brain which escape food addiction, and create powerful incentives that in fact many people for eating.2 In addition, need external help to do positron emission tomoso. These simple observagraphic (PET) imaging Figure 1: Doesn’t simply looking at these pictures make your mouth water? tions from our everyday studies have shown both

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Letters obesity and drug dependence to be related to reduced levels of dopamine receptors2 which leads to a need for greater amounts of a substance to achieve intoxication – a conclusion that relates back to tolerance, a criterion for addiction. Other studies have shown that consumption of certain foods such as alcohol and high-fat sweets can lead to changes in the opiate system by causing the release of endogenous opioids, which are psychoactive chemicals that can lead to addiction, in the brain. Furthermore, the administration of opiate blockers such as naloxone reduces the reinforcement value of high-fat sweets for binge eaters.2 Although research on humans has not been carried out extensively, rats were found to triple their daily sugar consumption when fed an intermittent diet of sucrose, exhibiting possible tolerance to sugar-rich foods. Another study has shown that when animals on a high-sugar diet were deprived of access to sugar, their body temperatures dropped and the animals exhibited behaviors associated with withdrawal, such as agitation and anxiety.2 From an evolutionary perspective, one could argue that humans have cravings for energy-dense foods and engage in behavior such as binge-eating in order to increase energy stores and provide protection against possible famine. When it used to be difficult to obtain high-energy foods, this biological propensity would have been adaptive. However, nowadays, seeking high-energy food is likely to lead to excessive food consumption because it has become readily available.2 Despite indications that food addiction may exist, it is essential to note that research in this area is complicated. Using the aforementioned criteria for addiction, it may seem easy to simply categorize food addiction as a formal “addiction”. However, this is not possible as food, unlike other addictive substances, is necessary for survival and is consumed from birth. According to psychiatrist Nora Volkow, director of the National Institute on Drug Abuse, there are multiple factors that determine what people eat and how much they eat. Unlike the consumption of addictive drugs, eating is a complex behavior involving many hormones and systems in the body, not just the reward system, which regulates behavior by inducing pleasurable effects8. It is necessary for researchers to take into account that there are differences between drug addiction and the intense compulsion to eat food.

Our generation may be the first generation in a long time to have a lower life expectancy than our parents’ generation.

One of the central problems causing this is the so-called obesity epidemic. Research on food addiction may be essential to solving this problem, and it is clear that further research into this area will benefit our generation and many generations to come.

References: 1. International Obesity Taskforce. The Global Epidemic. Retrieved from http://www.iaso.org/iotf/oesity/obesitytheglobalepidemic/ 2. Gearhardt, A. N. (2009). Food addiction: An examination of the diagnostic criteria for dependence. J Addict Med,3(1), 1-7.

3. IBISWorld.(2011, October). Weight loss services in the US: Market research report. Retrieved from http://www.ibisworld. com/industry/default.aspx?indid=1719 4. Food Addicts in Recovery Anonymous. (2010). Retrieved from http://www.foodaddicts.org 5. Oxford University Press (2012). Oxford English Dictionary.

Retrieved from http://www.oed.com/ 6. Pain & Policy Studies Group (2012, March 20). Glossary of Terms. Retrieved from http://www.painpolicy.wisc.edu/glossary. htm 7. Valorie, V. H. (2010). The obesity epidemic: the role of addiction.

CMAJ, 182 (4) 8. Hellmich, N. (2007, July 10). Does food ‘addiction’ explain explosion of obesity? USA Today. Retrieved from http://www. usatoday.com/news/health/2007-07-09-food-addiction_N.htm 9. Rochman, B. (2012, February 2). Should sugar be regulated like alcohol and tobacco? read more: http://healthland.time. com/2012/02/02/should-sugar-be-regulated-like-alcohol-andtobacco/?iid=hl-main-feature Figure 1: Royalty Rental. (Photograph). (2011). Wedding reception dessert stations for fun! [Print Photo]. Retrieved from http:// chairandtablerentals.com/2011/07/wedding-reception-dessertstations-for-fun/

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Thesis Interview

Interview with Nina Yoo ’12 Reconstitution of C. Elegans gamma secretase Sooji Choi ’14 Major: Biology Thesis advisor: Professor Caroline Goutte Can you explain your project?

My thesis is basically a continuation of Emma Fink’s thesis, which was to isolate a protein complex, gamma-secretase, which is involved in the Notch signal pathway. Notch signal pathway mediates cell-cell communication that controls gene regulation mechanisms. A ligand (blue; see Figure 1) from outside the cell binds to the Notch receptor (purple) on the cell membrane which activates the Notch pathway. This activated Notch receptor cleaves its intracellular domain (green), which floats away from the membrane and enters the nucleus to modify gene expression.

Gamma-secretase (red) is an internal protease that catalyzes the cleavage of this intracellular domain of Notch receptor.

It is important to note that Emma’s work was also a continuation of another thesis. Rebecca Resnick ’10 intrigued the idea of analyzing the different types of gamma-secretase.

Gamma-secretase is a 4-protein complex. Presenilin, one of the proteins that make up the complex, can come with two possible subunits, HOP-1 or SEL-12. These two types of presenilin are interesting because even though their molecular structures are very different, they seem to serve the same function in the cell.

So, Emma created two yeast cell lines with the two different types of gamma-secretase (HOP-1 and SEL-12), which are available only in mammalian cells, and observed the different activation levels. She constructed gamma-secretase in yeast by building plas-

Figure 1: Notch signaling pathway

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mids that compose components of gamma-secretase.

The goal of my project was to continue the construction of C. elegans gamma-secretase in yeast to create a biochemical model of the complex, and assay the yeasts to observe the levels of gamma activity between two presenilins. Emma engineered the expression of gamma-secretase, but she did not finish the rest of Notch pathway. Therefore, I conitnued her project by creating the Notch receptor model in yeast cells. I used cloning, PCR (Polymerase Chain Reaction), and yeast transformation techniques to transplant proteins required for Notch pathway in yeasts.

What are some challenges of writing a biology thesis?

A biology thesis is difficult for many reasons. The most frustrating thing about molecular biology is that everything is at the microscopic level; it is hard to visualize what is going on inside the cell.

What do you enjoy the most about your thesis and what is significant about it?

Science is a difficult field. It is filled with failures and inconclusive results, but I have been fortunate enough to have some success with my project. These moments of success have helped remind me of why I enjoyed science in the first place.

I think my thesis is significant because it shows that scientific research is never ending. Rebecca’s thesis lead to Emma’s and I’m continuing Emma’s.; our work all integrates together. I’m curious to know how other students will continue this series of research.

Also, it is interesting to see how biological studies are interrelated. For example, the gamma-secretase is found in both C. elegans and mammals. Now, we are taking something from mammalian cells, and reconstituting it in yeasts to experiment and analyze.

Any memorable or funny episodes?

Last semester, I accidentally locked myself out from the lab. It was late at night and I had gone to take a photograph of some gels without my ID card and lab keys. I had forgotten that one of the doors in the lab automatically locks when the door is closed! Panicking, I ran around Merrill and McGuire looking for another thesis student to let me into my floor. Since then, I have been overly paranoid about bringing my lab keys and ID with me whenever I leave lab.

Thesis Interview Do you have any advice for future thesis writers?

The most important lesson I learned was that time management is the key to a less stressful thesis experience. Also, pick a topic that you are truly interested in. As for me, I was more interested in continuing the reconstitution of Emma’s yeast model than working with C. elegans. Thesis can be daunting at first, but if you try to do these two things, I am confident that everyone will have as enjoyable a thesis experience as I have had.

Figure 1: http://clincancerres.aacrjournals.org/content/13/22/6549/ F3.expansion

Polarized Petrographic Microscopes and the Study of Rocks Benjamin Lin ’12 Geologists who geometric figures constructstudy hard, crystaled such that the size of the line rocks routinely use radius in a given direction is polarized petrographic proportional to the index of microscopes to get an refraction. So isotropic maidea of the composition terials have an indicatrix that and textural relationlooks like a basketball: light ship of minerals within entering from any direction a sample. By cutting encounters a circular cross a rock into slices thin section, since the index of enough that light can refraction is the same in all pass through, they directions. But anisotropic are able to exploit the materials will have indicatrivarying crystallographic ces that look more like eggs and optical properties (or slightly flattened eggs), of different minerals to and the direction light enters identify and characterize determines what the 2-D the phases within rocks, shape of the cross section is. which then allows them When polarized light Figure 1: Polarized petrographic micorscopes allow geologists to determine vibrating in one direction to infer information including source magma, phases (left) within rocks such as the kyanite-ecologite rock on the cover enters an anisotropic crystal, protolith (the source rock (right) the light is split into two type prior to metamororthogonal (perpendicular) phic changes), and pressure-temperature-time paths, for instance. vectors in a process called birefringence or double refraction.

These are useful in reconstructing Earth’s tectonic history, as the Because the two different directions have different indices of minerals record changes in environmental conditions that reflect refraction, the components of light travel at different speeds. larger-scale geologic change.

Thus when they exit the mineral, there is a retardation or phase Microscopes with polarizing lenses are particularly useful shift in one of the components relative to the other. This phase for this task, because they can help us identify minerals based on shift causes constructive and destructive interference when the certain properties, beyond morphological ones, that are hidwaves recombine in a polarizing lens beneath the microscope den when only using plain light. In physics, it is well established eyepiece called the analyzer, creating a variety of colors when that light changes speed in different mediums depending on the viewed in the eyepiece. These interference colors and patterns medium’s index of refraction. Mineral crystals are interesting can be diagnostic for different minerals. A plate of gypsum with because most are optically anisotropic, meaning the index of a known birefringence can also be inserted above the analyzer, as refraction is different along different directions. Indices of refrac- this causes a particular phase shift in one direction and is used to tion can be thought of geometrically by using indicatrices: 3-D determine the orientation of different minerals.

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Letters

Sweet Dreams: A Sugar Rush (of Sorts?)

Alexander Li ’14

It is 3 AM. You are working on a math proof for your problem set due the next day but have been stuck on a single problem for the past 3 hours. You rub your eyes for a moment, but suddenly, the world shifts around you. You look around and see a massive pixilated exam paper monster – a parody of Pac man – headed straight towards you! You flee, but are unable to escape. However, once you are swallowed by the monster, you are bombarded by mathematics – everything you know that relates to your frustrating proof – and one idea strikes you. You spring up involuntarily, woken by that dream-inspired epiphany, and easily solve the most unintuitive proof you’ve ever done. It might seem a bit too convenient to be able to solve problems in your sleep, but there is a scientific basis for the insightfulness of dreams. After falling asleep, especially during rapid eye movement (REM) sleep, the chemistry of the brain changes, causing differences between our normal waking consciousness and dreaming consciousness. Some of the more notable features of dreams are their creativity and hyperassociativity which often lead to odd but interesting lines of thought.

One famous example of dream inspiration comes from the Nobel-prize winning physiologist, Otto Loewi. Otto reportedly dreamed of his procedure to test his hypothesis of chemical transmission of nerve impulses. On the first night of his dream, Otto woke late at night and scribbled down his experimental procedure. He was, however, unable to decipher his own scrawl and could not remember what he had dreamed about. After thinking about it for most of the day, Otto resignedly went to bed. Fortunately, he dreamed of the same procedure the following night, and this time he made the decision that earned him his Nobel Prize: upon waking up, he immediately went to the lab to test his dream-inspired procedure and successfully proved his hypothesis to be true.1 Where does the creative quality of dreams come from?

A recent article titled “Consciousness in Dreams” provides an explanation for this free-spirited nature – the dorsal lateral prefrontal cortex (DLPFC) and the locus coeruleus (LC) nerves are deactivated during REM sleep, which is when most dreaming takes place.2 These changes in brain activity distinguish the behavior of our dream consciousness from our normal waking consciousness.

The DLPFC is implicated in executive functions such as decision-making and impulse control.4 In one experiment, MRI scans of the DLPFC were taken to measure differences in activation during two different economic games: the Dictator game and the Ultimatum game. In these two games, there are two partici-

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pants, a giver and a recipient. The giver starts with an amount of money and has the option of giving some of it to the recipient.

In the Ultimatum game, the recipient can refuse any offer from the giver, which ends in neither of them getting any money. In the Dictator game, the recipient has no choice but to accept the offer from the giver, removing any strategic considerations from the game for the giver. Greater activation in the DLPFC during the Ultimatum game suggests that DLPFC activation is correlated with impulse control.4 In a more artistic setting, the brain of people performing Jazz improvisation also show deactivation of the DLPFC.2 You might also compare this mental state with that of a person actively engaged in a brainstorming session. These creative processes require spontaneity, which is only possible if a person does

Figure 1: A dream-catcher. A Native American invention that caught nightmares, allowing only good dreams through.

Letters not constantly filter what thoughts or ideas he expresses. Dreams display the impulsiveness of Jazz performers and brainstorming sessions through their inertia – a dream plays out by itself, with little, if any, conscious input or questioning. This is how the oddest events in a dream can be looked over with barely an exclamation of “that’s strange”, which would normally halt bizarre lines of thought. The lack of control that we possess over our dreams is one of the key contributors to a dream’s creativity.

In addition, it has been found that the LC neurons are silenced during REM sleep and this may play a role in the decreased activity of the DLPFC. The LC neurons innervate the cortex with norepinephrine – the DLPFC and LC neurons are active when a person is awake and both are inactive during sleep and the LC neurons also fire more strongly during increased vigilance and focus.5 In dreams, you tend to draw connections between things which are not necessarily closely related. This hyperassociativity of dreams can be explained by the decreased activity in the LC neurons and the DLPFC.2 Our inability to control the course of a dream enables the dream to follow random tangents.

The ability to switch lines of thought is critical to creative thinking; dreams are conceived of as creative in part because they can so easily switch between different ideas due to their hyperassociative nature.

Considering the volatility of a mind in mid-dream, it could be hard to imagine that someone could focus adequately to solve a complicated problem from a (imaginary) midterm (surely they are worse in the imagination, right?). Studies have shown, however, that the content of a dream is influenced by one’s emotional involvement with a subject.3 Stress before a test, for example, makes it more likely for you to have dreams about said test. However, it has also been found that focused activities such as reading are less likely to occur than less focused activity such as talking to friends.3 Well, no one said that you could, or should, rely on dreaming to cram for your exams either. Otherwise, we would all be straight-A students.

In addition to being purely entertaining, dreams are an incredible medium for exploring ideas. Each time you dream, your mind constructs an entire world from your memories for you to experience. Your mind simulates interactions with other people and the environment, sometimes following the rules of reality and at other times completely straying from them. It is as if your mind is creating a play (the dream) in which the characters are often people who you know intimately. The creativity of the brain is truly demonstrated in these uninhibited nightly escapades.

I suppose it is not too different from the mindset I was in, however, when I came up with the title for this piece in a moment of inspiration. Here’s the metaphor: sugar rushes = uncontrolled, hyper. Dreams = uninhibited, creative, volatile. Mix these with the nighttime farewell “sweet dreams” and – ta da! – (creative?) title.

References 1. Justin, R. (2006). Otto Loewi’s Great Dreams. Retrieved from http://xnet.kp.org/permanentejournal/summer06/otto.html 2. Kahn, D., Tzivia, G., (2010, September 24). Consciousness in Dreams. International Review of Neurobiology. 92, pp. 181-195.

Retrieved from http://www.sciencedirect.com/science/article/ pii/S0074774210920096 3. Makwana, A., Hare, T., (2012, March 7). Stop and Be Fair: DLPFC Development Contributes to Social Decision Making.

Neuron. 73 (5), pp. 859-861. Retrieved from http://www.sciencedirect.com/science/article/pii/S0896627312001717 4. Gottesmann, C. (2008, April 22). Noradrenaline Involvement in Basic and higher Integrated REM Sleep Processes. Progress in Neurobiology. 85 (3), pp. 237-272. Retrieved from http:// www.sciencedirect.com/science/article/pii/S0301008208000452 5. Schredl, M. (2010, September 24). Characteristics and Contents of Dreams. International Review of Neurobiology. 92, pp.

135-154. Retrieved from http://www.sciencedirect.com/science/ article/pii/S0074774210920072 Figure 1: http://www.fanpop.com/spots/dustfingerlover/images/12824821/title/colorful-dreamcatcher-photo

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Thesis Interview

Interview with Brigit High ’12 Clozapine’s Effects on Rat Anxiety Behavior in the PCP-Induced Schizophrenia Model Dan Rivera-Lanas ’14 Major: Neuroscience Thesis advisor: Professor Sarah Turgeon Could you tell us about your thesis?

It’s entitled “The effects of clozapine on anxiety behavior in rat phencyclidine-induced schizophrenia model”. I’m working with Professor Turgeon, who works with the PCP model of schizophrenia. Specifically, we use a method where we give the rats an acute injection of PCP, a dissociative drug whose effects are similar to schizophrenic symptoms, and then have them withdraw from it. I think we’re the second lab to be using this model of PCP administration.

Specifically, I’m looking at the effects of Clozapine, an antipsychotic used to treat schizophrenia, on attenuating the sexually dimorphic effects that PCP has on anxiety in male and female rats. We’re looking at anxiety, which is very common in schizophrenics to the point that it could be considered a symptom, or, in patients who have some kind of anxiety disorder, it could be considered another subgroup of schizophrenia. It’s pretty common.

Results from Professor Turgeon’s lab from previous years have shown this sexually dimorphic effect of PCP on anxiety, where PCP causes an anxiogenic (causing anxiety) effect in males, but an anxiolytic (reducing anxiety) effect in females, which is interesting because schizophrenia itself has a bunch of sexual dimorphisms between men and women, particularly in the age of

onset and the different symptoms that are expressed, to the point that a lot earlier some people though they might be two separate diseases, but it seems like it’s more of a gender and culturally mediated reaction to the effects of the same disease.

We had a total of 48 rats and divided them into groups of male and female, but also groups of PCP administration, groups of Clozapine administration, and then controls for each of those.

The first day we would give the rats PCP, have them withdraw from it for a day, and then begin treatment with Clozapine for ten days. Every twelve hours you have to give them an injection of Clozapine, and then at the end of that trial we gave them IP (intraperitoneal) injections (the injection of a substance into the body cavity). After that, I tested them behaviorally in a light/dark emergence assay, which is a commonly used measure of anxiety that takes advantage of rats’ natural aversion to light, open spaces.

What kind of research would you like to pursue next?

Maybe to further explore this problem?

Well, the results of my thesis didn’t find an effect of Clozapine on anxiety, period.. Again, we went into it not really knowing what to expect because there haven’t been that many studies of Clozapine on anxiety, really. Most studies have either found no effect of Clozapine on anxiety, or some studies have found precipitated (sudden onset) anxiety symptoms because of Clozapine treatment or some sort of association between Clozapine and inducing anxiety. So it’s not completely unsurprising that it didn’t show any effect, just because of the inconsistency in studies that have somewhat explored this problem.

How much time have you spent on your thesis so far?

It kind of fluctuates on a weekly basis. Sometimes I’ll madly work on my thesis, and then I’ll have other things due and maybe spend a couple days without working on it. I honestly don’t know, it’s increased steadily over the semester.

Figure 1: Crystal PCP

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Any advice to any students considering a neuroscience thesis?

Finish your introduction in the fall. I didn’t, and it’s really coming to bite me in the ass.

Thesis Interview References Figure 1: http://www.wichita.gov/CityOffices/Police/Investigations/Special+Investigations/PCP.htm Figure 2: http://www.taconic.com/wmspage.cfm?parm1=4329

Figure 2: Sprague Dawley rats used in Brigit’s work.

What are your future plans?

Well, I’m eventually hoping to apply to some kind of graduate school, probably an MD or an MD/PHD program would be great, but I’m not going to do that right away; I want to take some time to do other research. I don’t quite know where I’m going to be; I’m still waiting to hear back.

What’s the most important thing you’ve learned so far from your thesis?

I think I’ve really learned how to independently organize an experiment. Even though it’s a project that is somewhat assigned, you have input over how to manage and plan it, especially with the timing of my experiment; again, it was very time-dependent; I had to come in every twelve hours to inject my rats; I can’t leave campus for the weekend whenever I have a trial. I think it’s really helped me to look at the small details of what I’m doing and organize them in a coherent way, because the nature of the experiment itself forced me to do that. I feel like that’s where I’ve improved the most, being able to independently do that.

Do you think these are skills that will help you in the future?

Definitely, you have this massive binder full of all this work you’ve been doing for the whole year. It’s intimidating, but also you know that you can do it, because other people have done it before you. But I’ve enjoyed working on my thesis, I really love the work that I’m doing, and Professor Turgeon’s lab is really interesting.

How was working with Professor Turgeon?

I really like working with her. She’s always very available, by email, and the few times I’ve had to call her on the phone, which have been unfortunate things you don’t ever want to have to call your advisor late at night on the telephone about, she’s also been extremely helpful.

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Hallucinations Are All in Your Head: The Brain, That Is Sonum Dixit ’13 Introduction It is 2 am and you are at the Seeley Mudd computer center. After pulling too many all-nighters in a row, you may have started to see or hear things on your computer screen that actually did not exist, commonly known as hallucinations. This may be an entertaining story to tell your friends at Val the next day, but you may not have realized that major brain changes occur during hallucinations. Hallucinations are also not a laughing matter to individuals who experience them frequently and cannot control them.

Hallucinations are not a modern day invention—they have been documented throughout history. The word hallucination is derived from the Latin root “allcinti,” or “wandering of the mind.”1 The Ancient Greek philosopher Socrates supposedly heard voices that guided his decisions as far back as the 4th Century BC, while people in the Middle Ages thought hallucinations were manifestations of the devil.2 However,“hallucination” did not become an official term until the French psychiatrist JeanÉtienne Dominique Esquirol described it as “a strong conviction of a sensoryexperience, when there is no external stimulus affecting the senses in a corresponding manner.”3 Hallucinations have multiple causes and have been documented in people of all age groups. They can be auditory-visual, musical, or olfactory and can be caused bymany types of drugs, such as recreational drugs or beta blockers used to treat hypertension. Hallucinations also occur as a result of schizophrenia,

Figure 1: Do you think you might be hallucinating?

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Alzheimer’s-induced dementia, and sleep disorders.

Although we know that hallucinations have many causes, there is no empirical data available about the frequency or demographic distribution of hallucinations. Oftentimes people are hesitant to reveal that they experience hallucinations, for fear of being labelled crazy.4 In addition, hallucinations are difficult to self-report because one may not be able to differentiate between imagination, vivid memory or actual hallucinations. There is an increasing amount of proof that certain regions of the brain are activated during hallucinations, but until we have access to more case studies, we will not have a complete understanding of what occurs in the brain during a hallucination.

Hallucinations, Neurons and the Brain Neurons are usually known to fire and transmit information in only one direction, but this is not necessarily the case during a hallucination. Jerzy Konorski, a Polish neurophysiologist, was one of the first scientists to realize “that there are not only afferent connections from the sense organs to the brain, but ‘retro’ connections” going in the opposite direction,4 indicating that the brain can sometimes activate sensory organs without stimuli. This activation of sensory organs is what produces hallucinations. Ted Griffiths, a cognitive neurology professor at the Newcastle Institute in Britain speculates that when people listen to music, the brain amplifies the important sounds and filters out random noise in the environment. In individuals who hallucinate,

Letters however, neurons still fire when no sound enters the ear. Griffiths says that the brain can conjure memories (aka hallucinations) as a result of this neuronal firing.5 Sensory input normally inhibits flow of neuronal impulses from the cortex to the periphery, but lack of it causes this flow to occur. As a result, the individual sees or hears things that are not actually present; he or she hallucinates. These are called release hallucinations because hallucinations are “released” by removal of sensory input. In absolute silence or darkness, off units – sensory neurons that are activated when stimuli are absent – continue to fire, which inhbit the flow of neuronal impulses from the brain cortex to the peripheral neurons.4 Release hallucinations are often as vivid as real sights or sounds, but do not occur nonstop.

Several functional Magnetic Resonance Imaging (fMRI) studies have shown how hallucinations can activate certain brain regions. This may seem contradictory because it was stated earlier that sensory input to the brain inhibits hallucinations; however, the brain parts that project neurons to sensory organs are activated during a hallucination. In many schizophrenic patients with auditory-visual hallucinations, the volume of the superior temporal gyrus (STG) is found to be lower than that in normal patients.7 The STG is crucial in speech processing, indicating that speech impairment may somehow be related to hallucinations.7

in their hallucinations. So Hugdahl’s group created a device that plays different sounds in each ear. The idea behind this apparatus, which can be plugged into cellular phones or other electronics, is to help schizophrenic patients focus on the sounds in one ear and ignore the sounds in the other ear. Ideally, this should help them tune out their hallucinations and instead focus on sounds in the outside world. This device has already been tried on two patients with positive results,6 but more trials need to be performed and it is unknown whether this device would help people who do not have schizophrenia.

Mixed Results in Treatment for Hallucinations In Musicophilia, Sacks also describes the case of a 70 year old woman named Sheryl C., who was taking 60 mg of prednisone for hearing loss. One of the unexpected side effects was that she began to hear nonexistent sirens and trolleys, which later transformed into songs from the musical,“The Sound of Music.”

Her neurologist then prescribed Valium, a drug often used for the treatment of anxiety disorders, which did not treat the hallucinations. Sacks then recommended neuropentin, used to treat epileptic symptoms, because musical hallucinations are often a result of neuronal over-activation. However, the neuropentin caused Sheryl’s ears to ring and the hallucinations to intensify. Finally, her hallucinations stopped after she received a cochlear implant, a device that improves hearing by stimulating the auditory nerve.

However, in other patients, cochlear implants have induced hallucinations.8 The details of how disruption and manipulation of signals from the auditory nerve cause musical hallucinations are still unknown.

A team of Norwegian scientists led by Kenneth Hugdahl created a device that could help people with schizophrenia focus less on their hallucinations (i.e. inner voices) and more on real voices. In a person with schizophrenia, neurons are activated when they hear inner voices, but they are not able to hear external voices at the same time.6 Hugdahl’s team found that these patients showed virtually no activation in the frontal lobe, indicating that schizophrenics lack the ability to hear real sounds while they are hallucinating, which is why they may seem “zoned out,” so to speak. The frontal lobe is crucial for impulse control, and if it is not activated, patients have a harder time ignoring the voices

References 1. hallucination. (n.d.).Dictionary.com Unabridged. Retrieved April 22, 2012, from Dictionary.com website: http://dictionary. reference.com/browse/hallucination 2. Ohayon, M. M. (2011, November 19). Historical Perspective on Hallucinations. Retrieved April 2012, from Sleep-Eval Research.

3. Vercammen, A. (2009). Cognitive and Neural Processes of Auditory-Verbal Hallucinations in Schizophrenia: Evidence from Behavioral and Neuroimaging Experiments. Doctoral Thesis, 1-57.

4. Sacks, O. (2007). Musicophilia: Tales of Music and the Brain.

New York: Alfred A. Knopf.

5. Zimmer, C. (2004, February 24). Can’t get it out of my Head: Brain Disorder Causes Mysterious Music Hallucinations. The Sunday Telegraph Magazine.

6. Lie, E. (2012, February 3). When hallucinatory voices suppress real ones. Retrieved April 2012, from The Research Council of Norway: http://www.forskningsradet.no/en/Newsarticle/When_ hallucinatory_voices_suppress_real_ones/1253973009968?WT. ac=forside_nyhet 7. Sun, J., Maller, J. J., Guo, L., & Fitzgerald, P. B. (2009). Superior temporal gyrus volume change in schizophrenia: A review on region of interest volumetric studies. Brain Research Reviews , 14-32.

8. Auffarth, I. S., & Kropp, S. (2009). Musical Hallucination in a Patient After Cochlear Implantation. The Journal of Neuropsychiatry and Clinical Neurosciences , 230-231.

Figure 1: Kubrick, S (Producer & Director). (1968). 2001: A Space Odyssey. Los Angeles: MGM.

Conclusion Scientists have noted that physicians often do not pay proper attention to patients who experience musical hallucinations, dismissing the phenomenon as ringing of the ears when that is actually not the case.5 Although we know that hallucinations activate certain brain regions, scientists still have to investigate brain mechanisms in order to make sense of hallucinations and why they occur. Until then, those who hallucinate will have to endure repetitive songs, sights and sounds against their will.

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Letters

The Code of Life Threatened: DNA Double-Strand Breaks and How Life Combats Them Maile Hollinger ’15 The DNA double-strand break is a very real threat—but our cells can fight back.

In the time it takes for you to read this sentence, approximately 200,000 gamma rays will have passed through your body.1 These ionizing rays penetrate skin, causing damage to cellular structures crucial to everyday function, like the cellular membrane and mitochondria. However, the most lasting damage gamma rays can inflict is on the DNA. Gamma rays add energy to DNA, breaking the bonds that hold the nucleotides and backbone together. With an average of 200 million gamma rays passing through your body per hour, it is amazing that cellular DNA is even viable after 24 hours of life. Yet, DNA provides a faithful genetic blueprint for every cell produced, despite damage not only from gamma rays, but also free radicals, faulty enzymes, and even DNA replication. Therefore, there have to be multiple ways in which the cell can repair its DNA and survive.

been snapped in half would be the DSB. But in the cell, getting a new set of chromosomes isn’t as simple as going to your local hardware store. That is why the cell has evolved specific mechanisms to respond to DSBs. DSB response: a life-and-death situation Despite repair mechanisms that are fairly efficient at stopping DSBs from affecting cell function, sometimes the damage is too great and the cell must go through programmed suicide, known as apoptosis. Typically, apoptosis is used as a last resort – that is, if the cell cannot repair its DNA by the two main repair pathways for DSBs (discussed later).2 If the DNA is not repaired, then a variety of proteins prepare the cell for death by signaling other proteins to participate in two different pathways: mitochondrial and death-receptor-driven. In mitochondrial apoptosis, the mitochondria open and release certain pro-apoptotic proteins, while in death-receptor-driven apoptosis, a death receptor

The DSB Of the different types of DNA damage, the most dangerous to the cell is the DSB, or double strand break. A DSB is a form of DNA damage in which a section of DNA is completely broken into two or more pieces. Other types of DNA damage, e.g. single-strand breaks and bonding of adjacent nucleotides, can be repaired relatively easily, as there is an adjacent strand for the repair machinery to use as a template for the repair of the broken strand. With DSBs, however, both strands have been broken and nucleotides may have been removed on either side; therefore, the repair mechanisms for DSBs have a more difficult time reverting the DNA to its original state.

Imagine a ladder: If you crack one side, you can reinforce it and make it whole again relatively easily, with the other half of the ladder as a template. If the entire ladder snaps, on the other hand, repairing it would be much more difficult, and it would be safer to buy a new ladder rather than Figure 1: DNA damage due to gamma irradiation use the old one. The ladder that has

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Letters on the surface of the cell is activated. In either case, the result is the same: caspases, proteins responsible for cleaving other proteins, destroy the cytoskeleton, DNA repair proteins, and the framework of the nucleus known as the nuclear lamina.3 While this seems harsh, it is a better alternative for the organism as a whole, as unrepaired DNA may cause a cell to become cancerous.

Unrepaired DNA may switch chromosomes in a process known as translocation and deactivate certain anti-cancer proteins – but we’ll talk about that later.

The cellular repair system While efficient at preventing cells from becoming cancerous, apoptosis is a rather destructive and extreme response to DSBs. A more practical alternative to apoptosis is DNA repair.

DSB repair comes in two different flavors: non-homologous end joining (NHEJ) and homologous recombination (HR).

In each body cell, there are two copies of each chromosome. Homologous recombination takes advantage of this by using the second copy of DNA as a template to repair the first. As seen in Figure 2, the broken strand invades the other strand of DNA, which is “opened” to allow the nucleotides of the broken strand to bind to the nucleotides of the unbroken strand. Then, repair proteins come in and fill in the holes in the DNA. There is debate as to whether the DNA forms four-stranded complexes in the process,4 but the result is two chromosomes with intact DNA. Non-homologous end joining is a relatively simple process. A protein complex specific to NHEJ holds the two broken

Figure 2: The two main DNA repair pathways. The different symbols represented in the key are different symbols represented in the key are different protein complexes involved in each pathway.

Figure 3: The Philadelphia chromosome, a chromosome created due to a transolocation between chromosomes 9 and 22. ends together; if there are missing nucleotides due to excessive DNA damage, the repair machinery will simply add in nucleotides until the two broken ends are compatible. Then, polymerases fill in the missing nucleotides and the strands are ligated back together.1 While simple, NHEJ is rather inaccurate, and may result in translocations, or the switching of two pieces of DNA to different chromosomes.

Of the two, NHEJ is more common in vertebrates, although HR is more common in single-cellular eukaryotes such as yeast. Both repair pathways are summarized in Figure 2. Of the two, homologous recombination is more accurate. It is used less often, however, because vertebrate DNA has very long noncoding regions, and a very accurate repair mechanism that takes more time is less advantageous than a quicker (if less accurate) one.

The significance of DSBs Of the different forms of DNA damage, double-strand breaks are considered the most dangerous. It is intuitive that double-strand breaks in the middle of a protein would prevent it from being expressed in the cell – thus, a double-strand break in the middle of a protein necessary for cellular function would result in cell death. Furthermore, multiple DSBs in the cell at once may result in a translocation, or the switching and repair of two DNA fragments onto different chromosomes or different areas of the same chromosome. Translocations are largely due to NHEJ, which is not DNA sequence-specific like HR. Such translocations can deactivate important proteins associated with cell-cycle arrest, apoptosis, or DNA repair. If this happens, then multiple cancer-preventing proteins are deactivated, bringing the cell closer to becoming cancerous.

Over 95% of patients suffering from chronic myelogenous leukemia – a specific form of leukemia characterized by a non-aggressive chronic phase before more aggressive phases – have the Philadelphia chromosome (Figure 3), which contains a translocation that brings two genes together. This pair of genes, The Amherst Element, Vol 4, Issue 2. Spring 2012

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Letters when expressed as one protein, causes too many stem cells to form white blood cells, which results in leukemia.5 By studying DSBs and how the cell repairs them, we may be able to use gene therapy to reverse the damage and even prevent DSBs from happening. The number of DNA-damaging agents such as gamma rays and replication errors that we encounter each day is enormous and may seem like too much for our genome to handle.

Thankfully, our body is well equipped with the internal machinery needed to prevent this damage.

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REFERENCES 1. Lieber, M. R., Ma, Y., Pannicke, U., and Schwarz, K. (September 2003). Mechanism and regulation of human non-homologous DNA end-joining. Nature, 4, 712-720. doi: 10.1038/nrm1202.

2. Roos, W. P., and Kaina, B. (2006). DNA damage-induced cell death by apoptosis. TRENDS in Molecular Medicine, 12(9), 440450. doi: 10.1016/j.molmed.2006.07.007 3. Hooper, C., and Killick, R. Apoptosis: mitochondrial and death receptor pathways. Retrieved from http://www.abcam.com/index.html?pageconfig=resource&rid=10388&pid=7#Caspases 4. Johnson, R. D., and Jasin, M. (2001). Double-strand-break-induced homologous recombination in mammalian cells. Biochemical Society Transactions, 29(2), 196-201. Retrieved from http:// www.biochemsoctrans.org/bst/029/0196/bst0290196.htm 5. Vachani, C., updated by Millar, L. B. (2007). Chronic Myeloid Leukemia (CML): The Basics. Retrieved from http://www.oncolink.org/types/article.cfm?c=8&s=30&ss=764&id=9591&CFID =44924716&CFTOKEN=30369883 Figure 1: NASA. (n.d.). Space Radiation Hitting Cell DNA [Digital image]. Retrieved from http://www.nasa.gov/exploration/ humanresearch/multimedia/index_gallery.html Figure 2: Crimi, Bob. 2001. [Digital diagram of NHEJ and HR pathways]. Retrieved from http://www.nature.com/ng/journal/ v27/n3/full/ng0301_247.html Figure 3: CML Society of Canada. 2007. [Digital diagram of Philadelphia chromosome]. Retrieved from http://www.cmlsociety.org/?q=node/14

Thesis Interview

Interview with Chris Lim ’12

Engineering small-molecule sensitivity into the WPD loop of Shp2

Kate Savage ’12 Major: Biochemistry Thesis advisor: Professor Anthony Bishop Can you explain your thesis?

The Bishop lab is interested in a specific class of proteins called protein tyrosine phosphatases (PTPs), which cleave phosphate groups on phosphorylated tyrosines residues on target proteins. Phosphorylation is critical in cell signaling as addition/ cleavage of negatively charged phosphate groups can dramatically change the conformation of proteins, which in turn causes a significant change in their functions.

The PTP I worked with for my thesis is Src homology-domain 2-containing protein tyrosine phosphate (Shp2). A particular structure I am interested in is the WPD loop, a highly conserved loop that begins with three amino acids: tryptophan (W), proline (P), and aspartic acid (D), hence its name. The aspartic acid (D) acts as a general acid/base catalyst in the dephosphorylation reaction, making the WPD loop catalytically important.

The goal of my project was to find ways to target specific PTPs such as Shp2. I engineered a cysteine-rich motif (cysteine, C: amino acids with sulfur atoms) into the WPD loop of Shp2, which will have affinity to a small molecule fluorescein arsenical hairpin binder, FlAsH. This method has two important advantages: 1) because the residues are highly conserved, this method can be extended to other PTPs in the superfamily, and 2) when FlAsH binds to the WPD loop and the catalytic D residue, Shp2 loses its catalytic activity. This allows us to use FlAsH as an “ON/OFF” switch to study Shp2 activity within the mutant cell, as well as a florescent marker.

Figure 1: Michaelis-Menten curves for WT and the P424C/S430C mutant with the cysteine-rich motif. The x-axis is the concentration of pNPP, a non-specific substrate for Shp2, and the y-axis is the average initial rate of reaction with a given concentration of enzyme. Black dots represent reaction with no FlAsH, and white dots with FlAsH. The catalytic activity of wild-type Shp2 was not inhibited by FlAsH (left), but the mutant was (right).

What are the challenges, difficulties, obstacles you have faced along the way?

Literature on Shp2 is growing, but relatively limited.

Solubility of Shp2 differs from other previously described PTPs, and it took a long time to find the right buffer conditions to get the protein to remain soluble after it was taken out of the cells.

It was very frustrating at times because the entire protein preps were rendered useless (“crashed out”) until the correct buffer was identified.

What have you enjoyed the most about your thesis?

I love love love the lab work. Though it varied throughout the year, I spent about 10 hours a week in lab. The myriad of techniques, including PCR site-directed mutagenesis, bacterial transformation, protein and DNA gels, protein expression and His-TAG purification, and biochemical assays, have been a great pleasure to learn, especially under Professor Bishop’s supervision.

How was working with your thesis advisor?

The best. I love the project and love how encouraging Professor Bishop has been! As an anecdote, a couple of weeks ago we went to a conference in San Diego (where Professor Bishop went to grad school) and he took us (myself and Gordy Lockbaum ’12, the other thesis student in our lab) to a really nice restaurant where he has been many times.

Did your thesis influence your career plans in any way?

For a short stint, I thought I wanted to go straight into graduate school for pure biochemistry and/or engineering because of the work I’d been doing on my thesis. I realized, however, that working in the “real world” for a couple years would be more valuable and give me time to really mull over my options.

Next year I will be teaching high school Physics at a private school in Richmond, VA. Still, my passion for scientific inquiry and research—as frustrating as it can be at times, especially when the correct buffer conditions for Shp2 were hard to find—was only reinforced by my work this past year in the Bishop lab.

What advice would you give to future thesis writers, and people who will be working in the Bishop lab next year?

Make a lab schedule. Be impeccably organized. Plan ahead and schedule your time, or else it’ll never get done!

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Sonum Dixit ’13 I attended several talks that focused on sex differences, including a minisymposium called “The Promise and Peril of Research on Sex Differences.”

One of the speakers at the mini-symposium, Dr. Larry Cahill from University of California, Irvine, discussed the neurological differences in male and female rats. He noted that a majority of current neuroscience studies only examine males because it is sometimes more difficult to get studies on females published.

Although many researchers are hesitant about addressing sex differences due to fear of being classified as “neurosexists,” Cahill concluded his talk by saying that it is “no longer justifiable to ignore half of the population.”

I enjoyed the talk because it made me question aspects of neuroscience literature that I had previously taken for granted. I realized that neuroscience does not necessarily answer questions about behavioral differences between men and women, but often reinforces stereotypes. Unfortunately, I felt that some of the talks just reinforced these stereotypes—as one study discussed stereotype threat experiences among women but did not suggest any potential solutions.

Although I wish the talks focused less on the speakers’ specific studies, and went more in-depth in discussing the pros and cons of incorporating sex differences into scientific research, I was glad to see that these speakers were thinking about the broader implications of their work and were willing to share them with fellow neuroscientists.

Alex Jaramillo ’12 Despite being a Biochemistry & Biophysics major, I very much enjoyed attending the conference. I ventured to several talks discussing the pathology of protein aggregation, implicated in diseases like Alzheimer’s disease (AD), Fragile X syndrome, and Huntington’s disease. These talks were particularly relevant to me as my thesis involves developing computational algorithms to understand the stability of proteins conformations, some of which are involved in these diseases. As my research is purely computational, it was helpful to hear about research efforts being undertaken to understand the pathogenic mechanism of amyloidogenic proteins from the perspective of neuroscientists.

One of the most interesting talks I attended at the conference was given by J. Tam, a graduate student in the laboratory of Stephen Pasternak at the Robarts Research Institute in Ontario, Canada. In the canonical pathway, amyloid precursor protein (APP) is trafficked to the cell membrane and cleaved by beta and gamma secretases, which produce Abeta, the amyloidogenic form of protein implicated in AD. Tam and his team have discovered novel pathways by which APP is internally trafficked from the production site at the Golgi apparatus to their final destination inside the lysosome. To achieve this Tam devised a series of ingenious experiments in which he used a photoactivable green fluorescent protein to observe the live intracellular trafficking of APP. He showed that in addition to being exported to the cell membrane, a significant percentage of APP is packaged and directly transported to the lysosome. This research transformed the scientific understanding of how pathogenic proteins arrive at their site of action and opened up a whole new set of questions to explore the disease. As a future PhD student, I find Tam’s work inspiring and I hope my own research will similarly have strong biomedical implications.

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The Society for Neuroscience, the largest community of neuroscientists in the world, held its 41st annual meeting in Washington DC this past November. We decided to take a break from Amherst one weekend to attend the conference.

The meeting was held in Walter E. Washington Convention Center, whose enormous halls bustled with over 32,000 attendees from all over the world. Below are our accounts of the enriching experience. *Sponsored by AAS and Interdepartmental Funds. Students who wish to attend science conferences may contact the Element.

Gabi Mateo ’13 Last semester I had the great opportunity of going to the annual Society for Neuroscience conference in Washington DC. I was able to stay overnight in the capital city of America, a place I had never been before!

I was surprised to find that the opening presentation for the weeklong conference was given by an economist, not a neuroscientist. Robert Shiller, Professor of Economy at Yale University and also a best-selling author, had recently published a book called Animal Spirits: How Human Psychology Drives the Economy And Why It Matters for Global Capitalism (2009). It was really intriguing to see how two seemingly opposite branches of science can be combined and how the brain can be approached from multiple perspectives.

Haneui Bae ’13 On Sunday night, we dragged our tired bodies (after an impromptu excursion to the White House) to the last lecture of our visit: Presidential Special Lecture called “The Basal Ganglia: Binding Values to Action” by Ann M. Graybiel PhD, professor of Brain and Cognitive Sciences at MIT. In the lecture, Dr. Graybiel described her lab’s latest research on a structure in basal ganglia called the pregenual anterior cingulated cortex (pACC). This structure had been previously found to be involved in cost-benefit evaluation in humans. Her lab microstimulated the pACC of macaque monkeys as they performed approach-avoidance decision tasks. In this task, monkeys make a decision about whether to approach or avoid a combination of positive (food) and negative (air puff) outcomes, cued in advance by visual stimuli. The visual cues consisted of combinations of red and yellow bars, whose length correlated with strength of the outcomes. Dr. Graybiel found that stimulation of certain regions of pACC biased the monkeys toward avoidance decisions, as if they had suddenly become more pessimistic. Treatment with anti-anxiety drugs was able to reverse this effect.

I was surprised and amazed that neuroscience research has progressed enough to tap into areas of advanced human mental function such as value judgment. Further research in the area will have not only scientific but interesting philosophical and social implications, which I am excited to hear more about in the near future.

Narendra Joshi ’13 The annual Society for Neuroscience conference in Washington DC was a huge event, with about 32 thousand registered attendees and hundreds of talks.

There was no way I could attend all of these events, so I had to pick the ones that I thought would be most interesting. The conference exposed me to many amazing research in the field of neuroscience and its numerous possibilities. I eagerly look forward to attending the next conference and strongly recommend it to anyone who is interested.

The presentation that I most enjoyed was by Moo Ming Poo, the famous neuroscientist who is a professor at UC Berkeley and the Institute of Neuroscience of the Chinese Academy of Sciences. I had previously read about his research and his efforts to foster neuroscience research in China and was excited to see him at the conference. His talk was about synaptic plasticity and the role of neurotrophins in this process. In particular, his lab has discovered the functions of a neurotrophin called brain-derived neurotrophic factor (BDNF) in axon growth regulation and in long term potentiation (LTP) of synapses. Currently, his research focuses on neuronal polarity and activity-dependent changes in synapses, especially spike timingdependent plasticity (STDP). Overall, his presentation conveyed the excitement of neuroscience research in an informative and engaging manner.

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Thesis Interview

Interview With Sarah Beganskas ’12 Mining for wildfire geochemistry

Tim Boateng ‘13 Major: Geology Thesis advisor: Professor Anna Martini Last summer, Sarah Beganskas ’12 travelled to Boulder, CO to conduct geomorphology/hydrogeology research for her thesis. At present, she is putting the finishing touches on her thesis, entitled “The geochemical impact of wildfire and mining on the Fourmile Creek watershed, CO.” Sarah did her thesis work as part of a Keck project, a program operated by a consortium of eighteen schools including Amherst, Smith, Mount Holyoke, Williams, and Pomona. The program is designed to provide geology students with the opportunity to investigate a topic of interest to them, and develop that research into a senior thesis. Participants conduct field research with professors and students from other consortium schools for four to six weeks during the summer before their senior year. In addition to working with their on-campus advisors at their host schools, students are also encouraged to stay in close contact with their research group from the summer as they work on their theses.

mostly within the Fourmile Creek watershed. Wildfire has a large impact on local chemistry and hydrology; burned landscapes have increased runoff and erosion compared to unburned landscapes, especially after precipitation events. Wildfires also slow the rate at which water is absorbed into the ground, increase the supply of erodible material by contributing ash, and burn away vegetation that might otherwise slow the downslope transport of water and sediment. This often causes flash floods and debris flows after a wildfire.

Although there is a large amount of geologic literature on the effects of both wildfire and acid mine drainage on watershed chemistry, the impact of both of these disturbances acting on the same region has never been studied. For this reason, Sarah chose to focus her thesis on developing a better understanding of the combined effects of wildfire and mining on the chemistry of a watershed, an area of research that will become increasingly important as global climate change potentially expands preexisting wildfire domains into mined areas.

BACKGROUND Sarah’s on-campus advisor is environmental science and geology professor Anna Martini. In the summer, Sarah worked Summer Field Work with Professors Will Ouimet (University of Connecticut) and Sarah began her research in July, travelling to the Front David Dethier (Williams College) as well as students Alex Horne Range through Boulder. She stayed at the University of Colo(Mt. Holyoke) and James Winkler (University of Connecticut) rado’s Mountain Research Station, located 15 minutes outside on the Colorado Front Range geomorphology project in Central of the town of Nederland. In the field, she collected samples of Northern Colorado. Her research was focused in the Fourmile water, sediment from the streambed, and where possible, flood Creek basin, located west deposits, at sites along several of Boulder. The area was of Fourmile Creek’s tributaries, mined for gold and other repeating the runs down the metals until the 1950s, watershed on different days and and abandoned mines still in different conditions during have an environmental her five weeks of field work. impact on the watershed, She also took measurements of generating increased the streams’ discharge and water acidity (sulfuric acid is conductivity (a measurement of produced as a by-product the total ion concentration in a of the oxidation of ore water sample) at each site. deposits) and the precipiLiving in Colorado and tation of heavy metals and getting to do her fieldwork there sulfate. In addition, the were two of Sarah’s favorite area was recently severely parts of her thesis experience. burned during a wildDuring her time in Boulder, fire which occurred on she also had the chance to help September 6, 2010. The the other two students and her fire burned about 26km2, Figure 1: Burned landscape. (Photo by Sarah Beganskas) field advisors with field work

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Thesis Interview for their own research. Although every Keck participant has an individual research topic, they often work together as a team to get things done more efficiently.

“When you’re in the field, you each work on your own individual project and collect your own samples, but a cool part of the program is that you get to spend a lot of time helping others with their field work, especially if one of you has a lot that needs to get done in one day, like me. With water chemistry, it is often important to sample and measure everything in one day; I had over two dozen sites to sample. It’s nice for your own research in that you have the help of other students and advisors when you need it, and it’s also nice that you have the experience of working on other peoples’ projects too.”

DATA COLLECTION When she returned to Amherst, Sarah began analyzing her data. The first step of this project involved using ArcGIS (a computer program which allows you to spatially analyze data in three dimensions) to delineate the watersheds of the tributaries which she had sampled. The locations of many mining sites were not noted on published maps, so Sarah constructed her own maps, combining her field observations with satellite imagery and with historic mining data. From these maps, she could then quantify the fire intensity, bedrock geology, degree of mining disturbance, and slope of each watershed.

Sarah’s samples from her summer field work consisted of essentially two kinds of samples: samples of water from tributaries and samples of sediment and flood deposits. To evaluate the composition of her water samples, Sarah employed a variety of lab techniques. She performed alkalinity titrations on each sample to measure the concentration of bicarbonate in the water, used ion chromatography to measure concentrations of other major anions (SO42–, NO3–, Cl–, and F–), ICP-OES to measure major cations (Ca2+, Mg2+, Na+, and K+), and ICP-MS to detect trace metals (e.g., Mn2+, Fe2+, Zn2+, Cu2+, Ni2+). She also used an isotope analyzer to measure the isotopic values of δ2H (the relative abundances of heavier vs lighter isotopes of hydrogen) and δ18O in order to trace the sources of these samples. She then combined this information with her field measurements of discharge and water conductivity.

To analyze the sediment samples, Sarah used an elemental analyzer to determine the Carbon-Nitrogen ratios, loss on ignition to measure the amount of organic carbon, and X-ray fluorescence to measure the composition of both major oxides and trace metals. She also determined the amount of mercury in each sample using a Hydra-C mercury analyzer, and looked for differences in mineralogy between the samples from mined and unmined tributaries using a scanning electron microscope (SEM).

sediment chemistry. This process took several weeks.

Sarah found that wildfire correlated with large increases in most major ions, particularly sulfate (SO42-) and major cations (Ca2+, Mg–‑+, Na+, and K+), while mining correlated only with increased sulfate concentrations. This might be expected since sulfuric acid is one of the products of the oxidation of mining ore. Mining also correlated with increased concentrations of many trace metals, including Cd+, Zn2+, Ni2+, and Fe2+.

Sarah found that wildfire and mining combined to increase concentrations of sulfate by a greater margin than typically observed after wildfire or acid mine drainage alone. Overall, wildfire had a larger impact on major elements in streamwater and sediment than did mining, while mining dominated the impact on trace elements.

Sarah also investigated the water chemistry of Fourmile Creek itself, and, by interpolating the changes in concentration and volume between each of its tributaries, calculated that the influx of tributary water accounted for nearly 100% of the changes in water chemistry downstream along the creek. Thus, wildfire and mining dominated the streamwater chemistry of Fourmile Creek itself, in addition to its tributaries. Fourmile Creek, in turn, is a major tributary of Boulder Creek, which provides a source of water for the city of Boulder.

ADVICE TO FUTURE THESIS WRITERS What kind of challenges did you face while writing your thesis?

“My project involved a lot of hydrogeology, but I never took hydrology. It’s been a bit of a challenge to do a thesis that is unrelated to a lot of my coursework, but at the same time it’s great, because I get to learn more along the way. It also gives me a better idea of what I might want to research in the future.”

Do you have any advice for future thesis writers?

“Think a lot about your topic and advisor before you begin. Be patient, start working on it early, and continue working on it always. Everything is magnified when you do a thesis, in terms of things you shouldn’t do, like putting anything off until the last minute. You think ‘Oh yeah, I don’t have too much more to do,’ but then things come up, things go wrong, you need to redo things, labwork takes a lot longer than you thought it would… always budget more time than you thought you would need. A year goes by a lot faster than you might think.”

DATA ANALYSIS AND RESULTS When she had finished collecting sampling data, Sarah correlated these data with her GIS measurements of the fire intensity, degree of mining disturbance, and bedrock chemistry of each watershed she sampled, trying to pinpoint which variables influenced the concentrations of which ions. This allowed her evaluate the effects of mining and wildfire on streamwater and The Amherst Element, Vol 4, Issue 2. Spring 2012

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Letters

Demystifying the Electric Car Sam Ubersax ’15 Back in February, the AAS called a school-wide referendum on a proposal for a new electric car for ACEMS and a charging station on campus.

After the student body expressed strong support for the measure (82% in favor), the AAS agreed to provide an additional $40,000 (in combination with a $20,000 grant from the College) to provide a total of $60,000 that will go toward the purchase of a Chevy Volt and the installation of the charging station.

Given the large amount of money that is at stake here, is the transition to the Volt really necessary? What’s behind the recent buzz about electric cars, and are they a viable alternative to gasoline-powered vehicles?

History of the Electric Vehicle The birth of the electric car occurred much earlier than most people would believe. In fact, electric cars are almost as old as electricity itself. Before the perfection of the mass-produced internal combustion engine, electric cars which ran on DC (direct current) electric motors were developed around the 1850’s.² Electric motors, invented only a few decades earlier, transform electrical energy into mechanical energy through the interplay of two magnets, an electromagnet and a field magnet.¹ The electromagnet is created when a copper wire (the green wire in Fig.1) is tightly wound around a metal core known as an armature. When a current is run through the copper wire, the armature becomes magnetically polarized. The field magnet is fixed and induces rotational motion in the electromagnet as mechanical brushes (usually made of carbon, shown as red lines in Fig. 1) reverse the direction of electron flow in the electromagnet with every 180° rotation. This initial 180° rotation occurs spontaneously because of the attraction between the opposite poles of the electromagnet and field magnet. This reversal occurs because of the design of the commutator, a copper ring (also of green

Figure 1: A basic electric motor

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color in Fig. 1) mounted on the axle of the motor just like the armature. The ring is split into two crescent moon halves with a small space of separation between each half. Each half of the commutator is soldered to one end of the electromagnet.

To facilitate the magnetic reversal of the armature, the commutator rotates with the armature, while the two carbon brushes are fixed and connected to the source of direct current (i.e. the battery). Initially, one half of the commutator (we’ll call it C1) will be in contact with the brush that is connected to the anode of the battery, causing current to flow one way through the electromagnet. After a 180° rotation, C1 will be in contact with the brush that is connected to the cathode of the battery, causing current to flow the opposite way through the electromagnet. After the rotation, the other half of the commutator (C2) will accordingly be in contact with the anode brush. When the flow of current through the electromagnet reverses, its magnetic poles switch from north to south and vice-versa. Rotation of the armature (via the electromagnet) is accomplished through this continual reversal of magnetism, coupled with the fundamental attraction between opposite poles of the field magnet and the electromagnet. Without an external source of current, electric motors cannot function.

Improvements in batteries throughout the 19th century, especially the advent of the rechargeable lead-acid storage battery in 1859, greatly enhanced the functionality of the electric car. In the early years of the automotive industry, electric cars shared many advantages over gasoline powered vehicles. They had almost no vibration, noise, or smell. Furthermore, electric vehicles did not have the tricky gear shift system required by the four stroke internal combustion engine. Learning how to shift gears was often quite difficult for first time drivers. Towards the end of 19th century and into the first few decades of the 1900’s, people generally only needed cars for the short commute from their local town into the city.² Thus, there was no concern about a car running out of battery power because it did not have to be charged very frequently. In fact, around 1900 electric cars were more successful than either steam-powered or gasoline powered vehicles.

Letters The Advent of the Gasoline-Powered Vehicle However, several factors contributed to the rapid decline of electric cars.² The Industrial Revolution and the rapid expansion of the U.S. population fostered the development of an advanced system of roads that connected cities for the first time.

The extension of America’s roads increased demand for vehicles that could travel long distances—a demand that electric vehicles could not meet. The discovery of crude oil deposits in Texas and other locations across the country significantly lowered the price of gas. Finally, mechanization and the development of factories spurred the launch of Ford Motor Company, which was able to mass produce internal combustion engine vehicles at an extremely low cost to the consumer. Electric vehicles were still produced inefficiently and thus quickly fell behind. By the 1930’s, they were all but extinct from the American landscape.² The Electric Vehicle Industry Today Widespread concern about the environmental impact of the combustion of fossil fuels sparked a renewed interest in electric vehicles in the 1990s/2000s. Development of high powered lithium-ion batteries in the 1980’s also made possible the production of highway capable electric cars. In the United States, many incentives to purchase electric vehicles were instituted in the form of tax credits and rebates.4 Despite a general consensus that electric cars are better engineered and more environmentally-friendly, they are still costly, mainly due to the batteries. A recent study conducted by Harvard University has found that the benefits of not having to pay for gas are insufficient to make up for the disparity in initial cost between electric and standard models.5 More importantly, much progress needs to be made for the transition to electric vehicles.

The limited infrastructure of charging facilities severely hin-

ders potential sales. The petroleum economy has so become so thoroughly ingrained in our society that it will take a few decades to integrate the appropriate charging facilities with the vast network of oil rigs, refineries, pipelines, and gas stations. And the loss of jobs involved in the transportation of oil and its products across the country cannot be ignored either.

The Battery The most important component of any electric car is the battery, which powers the electric motor. Most manufacturers utilize the lithium-ion battery for several reasons: It is extremely light and highly energetic due to the high reactivity of lithium.

Lithium ion batteries deliver 150 watt-hours of energy per kilogram of battery.³ In comparison, lead-acid batteries (standard in gasoline powered vehicles) deliver 25 watt-hours of energy per kilogram of battery. Inside the outer metal case of a standard lithium-ion battery, three thin sheets of material are immersed in an organic solvent (typically ether) that allows for ion flow between electrodes. Lithium cobalt oxide serves as the anode and carbon is the cathode. The separator between the two electrodes is a sheet of microperforated (meaning that a small amount of ions can flow across the separator) plastic. The standard potential of the battery is about 3.7 volts, much higher than almost all competitors.³ In addition, an onboard computer is crucial to the operation of the battery. Unfortunately, it adds to the cost of this already expensive device. Components of this computer include several temperature sensors, a voltage converter and regula-

Figure 2: The Tesla Roadster, one of the most popular all-electric models on the market today

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Letters ity. Many have trouble visualizing a future society without streets teeming with electric vehicles, and if the ACEMS proposal is carried out, Amherst may play a role in beginning the transition to these amazing machines.

Figure 3: Schematic of a lithium-ion battery tor circuit to maintain safe levels of voltage and current, and a battery charge state monitor.³ Other Nuts and Bolts Obviously, an electric car needs more than a battery to function successfully. Upon the application of pressure to the gas pedal, multiple potentiometers regulate how much power the controller (central hub of the vehicle) will draw from the battery.

Potentiometers are simple electrical components that consist of a variable resistor, which inhibits the flow of electrons through a wire. Variable resistors are able to take on several values of resistance (measured in ohms, or volts/amperes). By varying its intrinsic resistance to the flow of electrons, the potentiometers regulate the amount of power that reaches the controller. The controller does not function unless the signals from the potentiometers match up precisely, preventing catastrophic engine malfunction in an emergency. A DC controller reads the signal from the potentiometer and accordingly pulses the power drawn from the battery more than 15,000 times per second. During pulsing, the amount of electricity drawn from the battery alternates between the correct amount and 0 in an infinitesimal period of time. For instance, if the gas pedal were pushed down 10% from its original resting position, the controller would direct the pulsing of current so that power would be drawn from the battery only 10% of the time. The power would be “off ” for the remaining 90% of the time. Thus, the controller dictates the proper amount of current transferred from the battery to the electric motor, which operates at the appropriate speed according to the initial applied pressure of the gas pedal.

Undoubtedly, the future development of electric vehicles will have an enormous impact on our country and society as we wrestle with the combining pressures of sustainable ideology, technological progress, scientific research, and economic real-

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References 1. Brain, M. (2012). How Electric Motors Work. Retrieved from http://electronics.howstuffworks.com/motor.htm 2. Bellis, M. (2012). History of Electric Vehicles. Retrieved from http://inventors.about.com/od/estartinventions/a/History-OfElectric-Vehicles.htm 3. Brain, M. (2006). How Lithium-Ion Batteries Work. Retrieved from http://electronics.howstuffworks.com/everydaytech/lithium-ion-battery.htm 4. “Notice 2009-89: New Qualified Plug-in Electric Drive Motor Vehicle Credit”. Internal Revenue Service. 2009-11-30. Retrieved 2010-04-01.

5. Lee, H. and Lovellette, G. (July 2011). “Will Electric Cars Transform the U.S. Vehicle Market?”. Belfer Center for Science and International Affairs, Kennedy School of Government.

Retrieved 2011-08-07.

Figure 1: Taken from http://www.howstuffworks.com/electricmotor-pictures.htm Figure 2: Taken from http://www.teslamotors.com/roadster Figure 3: Taken from http://www.howstuffworks.com/everydaytech/lithium-ion-battery.htm

Thesis Interview

Interview with Dang Trinh ’12 Stock Volatilities: Long Memory and Common Factors

Tianshen Rong ’15 Major: Math and Economics Thesis advisor: Professor Tanya Leise Can you briefly explain the scientific concepts of your project?

As an Econ and Math double major, I’m interested in using mathematical tools to analyze the financial market. More specifically, the first part of my thesis project attempts to use time series analysis to study the daily stock returns variation, or volatility, of SP 500 companies, which are 500 large capitalization companies in the United States. Basically, a time series is a sequence of data points measured at even time intervals. What I intend to examine is whether the historical trends of the stock returns series have any effects on the following stock returns trends. Traditional models used to do this, such as the Generalized Autoregressive Conditional Heteroskedastic (GARCH) and the Exponential GARCH (EGARCH), have not been satisfactory because they do not adequately describe the long-memory characteristic of the series. In my project, I attempt to address this problem by adopting the standard treatment of the LongMemory Stochastic Volatility (LMSV) model, and incorporating into it an Autoregressive Fractionally Integrated Moving Average (ARFIMA (p, d, q)). This has helped me confirm the existence of long-memory effects in the daily stock returns.

Subsequently, the second part of my project aims to identify the possible sources for these long-memory properties and find out if they have anything in common. To address this question, I have used the canonical correlation analysis, which is a process of dividing dataset into groups by company size and see what characteristics they have in common. Using this method, I have found strong evidence indicating common factors contributing to long-memory in volatility.

not grant the public free access to their dataset. So I had to make a compromise by using data from Yahoo! Finance. Second, the literature of this area is hard to understand because of my lack of higher-level background. But through this process I’ve really learned a lot of new theories and methods and become increasingly appreciative of how fascinating Math is. Finally, there is the problem with presentation. With the limited space of a thesis, I have to carefully choose what the important things are to say, how to present the results efficiently, what graphs best suit the purpose and so on.

What advice would you give to future math theses writers?

I would say, take as many courses related to your interest before senior year as possible, and choose a project that is doable within one year. It’s really easy to get overly ambitious. Also, for statistics majors, computer programming is an important skill to have when you deal with huge datasets and complicated computations.

What’s your plan after graduating from Amherst?

I’m joining the analysis group of a consulting firm in Boston, continuing with the quantitatively based studies that I enjoy.

Where did the idea of the project come from?

In the second semester of my junior year, I took a Math class called Time Series Analysis, which introduced me to using statistical tools to analyze stock markets. Then, in the fall semester of this year, I read a paper by Ruey Tsay, the pioneer of financial time series analysis, which inspired me to use his classic theories of the long-memory of financial returns to examine the recent data.

Have you met any challenges or difficulties along the way?

Plenty of them! First, obtaining the data was difficult.

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Thesis Interview

Interview with Nate Belkin ’12

TMEM16F in Ca2+-Activated Phospholipid Scrambling Activity

Kate Savage ’12 Major: Biology Thesis Advisor: Professor Patrick Williamson Can you explain your thesis?

My project is investigating a protein that was implicated in being responsible for a particular bleeding disorder called Scott syndrome. Scott syndrome is a rare congenital bleeding disorder that is due to a defect in platelet mechanism required for blood coagulation.

The cell membrane is composed of various types of phospholipids. These different types of lipids are uniformly distributed throughout the membrane, but are found only in certain membranes. My research focuses on one type of lipid called phosphatidyl serines (PS), which are mainly located at the internal leaflet of the plasma membrane. Scott’s syndrome is caused by a lack of scrambling activity of these PS to the external leaflet of the plasma membrane. PS is normally internalized to the inner leaflet of the plasma membrane by proteins called flippases. Phospholipids on inner and outer leaflets of the membrane cannot diffuse freely over to the other side. Thus, enzymes such as filppases are needed to transport the phospholipids between the inner and outer leaflets of the membrane.

When PS gets exposed to the outer leaflet during scrambling activity, it forms a scaffolding upon which other

Figure 1: Model of potential scrambling activity. The figure above shows the general shape of fluorescence which was observed in the scrambling experiments. If scrambling were to be observed, the red Ca2+ rate would occur. If no scrambling were to be observed, the blue Ca2+ rate would be observed. Note the designation of what the dithionite (diT) rate and the Ca2+ rates are in the figure above.

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protein interactions occur. This eventually leads to the activation of fibrin, which is one of the major players in blood clotting.

One protein, TMEM16F, was found to be the protein which, when mutated, causes Scott syndrome. It is not known, however, whether or not this protein is the actual scramblase protein or another protein that regulates scramblase activity.

My thesis addresses the major question as to whether or not TMEM16F is the scramblase protein. I have put the TMEM16F gene in an expression vector and put that vector in yeast. It should be noted that yeast do not have normal scramblase activity when induced with Ca2+, a regular activator of scrambling activity. I have run a number of experiments testing to see if this protein is a scramblase protein. Namely, we put the fluorescent probe in the inner leaflet, and then treat the cells with Ca2+. The expected fluorescence vs. time graph of the experimental data for the scrambling experiments, along with potential scrambling and non-scrambling activities are shown below in Figure 1.

If the gene turns out to be the scramblase protein, then I would expect to see a decrease in fluorescence in the cells upon Ca2+ ionophore treatment. The decrease in fluorescence in the cells would be caused by and can be explained by a molecule in the solution (dithionite) which quenches all probes put into the external leaflet of the plasma membrane. If TMEM16F is only a regulator of scramblase activity, then no drop in fluorescence would be expected.

TMEM16A, a homologue of TMEM16F, has been shown to be a Ca2+ activated chloride channel. Therefore, I have also designed a number of experiments to see if TMEM16F might also be a chloride channel of some form, using a fluorescent probe that has its fluorescence quenched in the presence of Cl- ions. If chloride channel activity is activated, then the fluorescence would drop in the yeast cells that are expressing TMEM16F. I found that TMEM16F does not display scrambling activity, though it does display significantly high levels of baseline chloride channel activity. Also, the Scott mutant TMEM16F-6 displays high levels of baseline chloride channel activity. The baseline chloride channel activity of TMEM16F and TMEM16F-6 were actually both either equal to or greater than TMEM16A, the positive control. My results have not elucidated the manner in which TMEM16F is responsible for regulating

Thesis Interview Ca2+-activated scrambling activity, though they have provided some interesting information about the baseline chloride channel activity of the TMEM16 family of proteins.

What are the challenges, difficulties, and obstacles you have faced along the way?

No experiments really work as planned. It takes a few tries to get the experimental method down to a proper method that is reliable. Also, lab equipment may be old and it is hard to know if a buffer might not be working any longer or at what step in the procedure you may have made a mistake.

What have you enjoyed the most about your thesis? What did you dislike the most?

I enjoy working on an independent, unique project that is my own work. It is an entirely different lab experience than school lab work or summer lab research when working for another post doc or Principal Investigator (PI). I have a new drive and enthusiasm knowing that this is my work and my project. It is exciting but also a burden at times. I feel like I have to make my project work, and that is really stressful because in reality, it is very difficult to generate meaningful data after just 9 months of scientific research. Also, the first two months are just really figuring out the lab and where everything is.

How many hours a week do you spend on your thesis?

Recently around 40-60 hours a week.

Any funny or memorable episodes while writing your thesis?

When I was writing my introduction at the end of last semester, I stayed up all night with my fellow lab mate in Merrill.

We literally spent all night on the fourth floor seminar room of McGuire and then went to the Donut Man before class started.

What is the most important thing you have learned from working on your thesis? And what advice would you give to future thesis writers, and people who will be working in your lab next year?

Always keep a positive outlook, especially when working in a lab. Experiments do not usually work, so keep trying and do not rush. Try to really understand where you went wrong and don’t be afraid to ask your advisor or anyone else where you may have been going wrong. Always keep good notes and once again keep positive.

How was working with your thesis advisor?

Good, we have become good friends. We talk about other things than my thesis. We talk about politics and sports as well. I also helped him move his chicken coop in his backyard!

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Letters

To Remember Or Not to Remember?

Alice Li ’13

It’s 2 A.M. before a midterm exam. As you sit at your desk, staring at your textbook until your head is pounding, you wonder why so little of the information seems to be sinking in.

Or, while taking an exam, your mind turns up a blank as soon as you see questions about material you know you memorized the night before.

At that moment, you might be wishing you had an eidetic, or photographic, memory. You wouldn’t be alone. From missed appointments to lost keys and forgotten names, bad memory is the bane of almost everyone’s life. Yet, as counterintuitive as it may seem, forgetfulness plays a crucial role in keeping our minds healthy—and even in enhancing our memory.

NOT JUST AN INCONVENIENCE: WHEN FORGETTING IS USEFUL In the recent BBC television series Sherlock, an astonished John Watson confronts Sherlock about the latter’s ignorance that the Earth orbits the Sun, to which Sherlock responds: “Listen. This is my hard drive,” he says, pointing at his head, “and it only makes sense to put things in there that are useful. Really useful. Ordinary people fill their heads with all kinds of rubbish, and that makes it hard to get at the stuff that matters, do you see?”

As shocking as we may find his lack of knowledge about the solar system, perhaps the detective does have a point. Considering how useful memory is for nearly every aspect of our REMEMBER THIS: FAST FACTS ABOUT MEMORY daily lives, one might think that forgetting would be evolutionarily AND FORGETTING disadvantageous. As it turns out, however, forgetting may play a Psychologists distinguish between two main forms of vital function in keeping our brains healthy. memory: short-term memory (STM) and long-term memory AJ is a patient with one of the only confirmed cases of (LTM). A new memory will pass through STM to LTM, where it hyperthymesia, a will theoretically remain disorder characterforever until you atized by an extraortempt to retrieve that dinary ability to memory. On the morecall specific items lecular level, when new from the patient’s long-term memories are personal history.2 created or consolidated, A hyperthymestic’s a series of chemical memory does not processes is triggered derive from the that remodels and use of mnemonic creates new synapses, strategies, and thus which are the junctions it has been proposed between neurons in the that hyperthymesia brain, in order to fainvolves an unusual cilitate communication memory system, between the neurons.1 rather than the We usually think use of a normal of forgetting as a loss memory system in of information from an unusual way.2 LTM, but the consensus However, in psychology is that AJ’s extraordinary information that makes memory might be Figure 1: A network of nerve cells. it to LTM essentially more of a burden remains there forever. If we have the ability to store memories than a blessing. Most of the information she can recall is trivial, for an indefinite amount of time, however, why are we unable to and she spends much of her time brooding over the past, rather retrieve all of that information? than focusing on the present or the future.2 It seems, then, that forgetting may serve an adaptive function, rather than being

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Letters

Figure 2: Unfortunately, forgetting isn’t as easy as pressing the delete key. merely a limitation of the brain.

Initial research into the potential benefits of forgetting surfaced in 1970. Psychologist Robert Bjork wrote that when learning new items, deliberate attempts to forget some led to enhanced memory for others.3 Later, Bjork, his wife, and graduate student Michael Anderson identified another reason for forgetting: deliberately remembering certain stored information obstructs later recall of similar material.3 The purpose of such forgetting, which they termed “retrieval-induced forgetting,” is to eliminate thoughts that might get in the way of more important information. Paradoxically, forgetting is thus vital for ensuring that our memories work efficiently. As it turns out, in recent experiments with working memory, those who could temporarily remember the most items were also the best at deliberately forgetting.3 The inability to forget can have other cognitive effects as well. Experiments have suggested that it may be correlated with depression and with ADHD. One study showed that depressed students remembered more words that they had practiced suppressing than other students did, while another study found that people with ADHD had more difficulty forgetting face-picture pairs.3 Too much memory, then, may lead to easy distractions or a tendency to dwell on negative emotions.

DON’T THINK ABOUT ELEPHANTS: IS FORGETTING INDUCIBLE? It may seem easier to forget desired information and remember unwanted memories than the other way around. But if too much memory can be detrimental, is it possible, then, to selectively forget certain negative or traumatic memories?

A few drugs that can induce forgetfulness have been identified. One is propranolol, traditionally used to treat high blood pressure and anxiety. As it turns out, propranolol blocks receptors in the amygdala, the part of the brain involved in emotional reactions, that are involved in signaling the brain to encode memories in response to emotional events. Test trials conducted in 2002 and 2003 found that administering the drug could prevent development of PTSD in patients, and a more recent study in 2005 found that patients with PTSD who took propranolol were able to reduce their symptoms in response to emotional

triggers.1 The key to this treatment involved taking the drug while recalling a memory. While before, it was believed that the synaptic connections involved in memory formation were stable and durable, now research supports the theory of reconsolidation, which states that when memories are recalled, or reconsolidated, they can be changed. The very act of retrieval changes memories, which researchers are now taking advantage of to possibly reduce emotional responses to memories.

Propranolol does not erase memory traces altogether; inhibition of an enzyme named protein kinase M-zeta (PKMzeta), however, does. PKMzeta is involved in transport of key proteins to synapses, which allow neurons to detect when a neighboring cell is firing, leading to information transfer.1 A drug that shuts down PKMzeta erases all memory, but a drug has been created to block synthesis of new PKMzeta for a few hours. In theory, a patient could selectively forget memories by recalling them and then taking the drug, which would prevent their reconsolidation.1 Drugs are not the only way to forget. It turns out that active suppression—trying to block a memory from one’s mind— can work as well. There are, however, major individual differences when it comes to ability to suppress unwanted memories. Some psychologists advocate trying to replace unpleasant memories with different thoughts, or simply doing something distracting when an unwanted memory comes to mind.3 Although none of these techniques are refined enough for clinical use, some researchers are hoping to be able to adapt forms of selective forgetting into therapy for conditions such as post-traumatic stress disorder and depression.3 CONCLUSION: A BLESSING, NOT A CURSE The reason why you might find yourself blanking out during a test is not just due to an inherent limitation of your memory. Forgetting is an integral part of having a healthy, functional mind that allows us to discard trivial information that would impede recall of important facts and also prevents us from dwelling excessively on the past. Without the ability to forget, we might become overwhelmed with all the details we would have to remember.

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Letters virtues of forgetting, much research remains to be done on the exact processes of suppressing memories. The idea of using drugs to erase or modify memories remains, of course, an extremely contentious area, fraught with moral and ethical considerations. However, if such therapies can alleviate PTSD, depression, and other conditions, they may be worth developing.

So the next time you find yourself forgetting someone’s phone number, don’t feel too bad: your brain is trying to streamline your memory so that, in the words of Sherlock Holmes, you can “get at the stuff that really matters.”

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REFERENCES 1. Piore, A. (2012). Totaling Recall. Scientific American Mind, 22(6), 40-45.

2. Michaelian, K. (2011). The Epistemology of Forgetting.Erkenntnis,74(3), 399-424.

3. Wickelgren, I. (2012). Trying to Forget. Scientific American Mind, 22(6), 33-39.

Figure 1: http://www.nobelprize.org/educational/medicine/ nerve_signaling/overview/index.html Figure 2: http://xkcd.com/379/

Feature

Medical school vs.

Graduate School?

Fan Feng ’13 Is medical school or graduate school the right path for me? As a science major you probably asked this question to yourself at least once. For some it is more than a passing inquiry. To make this important decision, we try to seek advice from our parents, teachers, and friends, but they may not fully understand your situation because they have not gone through the struggle themselves. We chronicle the experiences of three Amherst seniors: Sophie Kim ’12, Mable Lam ’12, and Akosua Korboe ’12, in order to help those who face the decision. Fan Feng ’13 talked to these seniors as they ready themselves for the diverging paths after Amherst, about how they made their career choices and how they prepared for them.

Sophie Kim’12 Why did you choose medical school?

I was influenced by my father who is a spine surgeon. I used to shadow my father, so I had an idea of what to expect of the profession. I loved seeing my father’s patients appreciate what he had done for them. I did have some doubts regarding career choice: medicine is a big commitment and nowadays we are facing so other many career choices. However, I eventually realized that medicine was satisfying to me because it relates to my science background and life experiences.

In addition, I like to interact with people and being able to help others makes me happy. Since I grew up with five younger siblings, I am used to taking care of others. At college, being involved with the Amherst Christian Fellowship provided me plenty of opportunities to meet and serve other people. Also I’ve been a mentor of Big Brothers Big Sisters since my freshmen year. I am passionate about mentoring, and I think that fits the medical profession as well.

Many students decide to take some time off before going to medical school. How did you decide whether or not to take gap years?

Some people take some time off because there are things they want to do first before going to medical school. In my case, I knew medicine was what I wanted to do and I felt like my past experience had prepared me for med school. In addition, I want to have a family after I graduate from med school, so I do not want to finish school later than I need to. Some people want to take a year off to become well-rounded, or to have a better chance of getting into med school. In my case, I thought that Amherst provided many opportunities, and there are be other ways to become well-rounded.

How did you decide which med school to go to and the area of specialty?

Family is very important to me so I wanted to go to a med school that is close to my family. I have always been interested in pediatrics and I’ve recently developed an interest in neonatology.

Figure 1: Neuroscience major Sophie Kim ‘12 from Minnesota will be attending University of Minnesota Twin Cities Medical School in the fall.

My interests are related to my personal experience. Although my twin brother and sister were born two months premature, they became healthy because of the medical care they received when they were born. I think it is also important to consider lifestyle when choosing a specialty. In my case, I want to choose a specialty that allows me to balance my profession with family.

Any advice for people who are preparing for the MCAT? I think upper-level science courses like Biochemistry (CHEM 331) can be helpful, because they allow you to become more familiar with terminology on the exam. For people who want to take the MCAT in January, make sure you balance the preparation of MCAT and your school work in the fall semester.

I had only one lab course that semester and I treated the preparation as a fifth class. I think it is important to make a schedule and block out study time throughout the semester.

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Feature

Mable Lam ’12 Mable Lam ’12, a chemistry major at Amherst, plans to pursue a PhD in biochemistry at UCSF TETRAD Program.

Why did you choose graduate school (over medical school, for example), and was it a difficult decision to make?

I was thinking about pre-med at first because I liked science and wanted to do something meaningful for society.

My parents would have loved me to be a doctor. Neither of my parents have a professional degree, so I didn’t actually realize that grad school was a possibility until college. At Amherst, I realized that doing research would fulfill my two desires as well, but still I believed that research should be reserved for the geniuses.

However, after two summer research experiences, one at Amherst and another at Stanford, I realized that the skills and the mindset required for research can be learned. As long as I really enjoyed it, it didn’t really matter if I was ‘born with it’ or not.

I’m going to grad school not because I know what questions I want to answer, but because I want to learn how to ask important questions and answer them.

I have always hinted to my parents that I didn’t feel med school was right for me. I get queasy at the sight of blood. So when I told them about my decision, they were not surprised.

Although they don’t completely understand the topics I will be researching, they are totally supportive.

How did you find your specific interests in biochemistry research?

I have broad interests and I still have no idea what specific system I want to study (so yes you can still get into graduate school even if you don’t know exactly what you want to do). But in general, I like to think like a chemist but study biological problems. I’m fascinated by interactions at the molecular level between proteins, small molecules, or macromolecules. Dissecting the forces at play, such as sterics, pi-stacking, and hydrogen bonding, really gives us the potential to manipulate significant biological processes by tweaking different atoms and functional groups.

I got some physical chemistry experience from working in Professor Marshall’s lab, but that work also helped me realize that I wanted to do wet work rather than computational. I was most excited about the research I did for Dan Herschlag at Stanford investigating the role of base positioning on catalytic rate enhancement on ketosteroid isomerase (KSI).

But I always had a lingering curiosity about organic synthesis, so I tried that for my thesis. I realized that I would rather work on answering biological questions than solving synthetic problems, so if I do use organic chemistry in the future, it will have a heavy biological application.

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Because your chemistry interests seem to somewhat overlap with biology and medicine, why didn’t you decide to pursue an MD/PhD degree?

You only get three years of research for MD/PhD programs. Then you have to go back and do residency, etc. for several years. This places you at a significant disadvantage if you want to apply for funding for research when you finally have your degree, since other PhD’s will have already gotten a head start with publications. I’m sure there are advantages for being MD/ PhD, but I know I primarily want to do research, so even though I would be interested in biomedical issues, I did not feel that the MD part was worth pursuing.

What factors are important for you when choosing schools?

Number of labs that interest me, general environment of graduate education, which you’ll get during interview weekends, as well as funding, prestige, and overall reputation in academia.

I found labs by asking Dr. Herschlag since he is familiar with my interests and other PI’s (principal investigator) in the field. I also explored webpages for research focus and recent publications. Many webpages are outdated, so if you’re really excited about one lab, you should really contact the PI via email or during the interview weekend to confirm that the lab is still aligned with your interests.

What do you see yourself doing in 5-10 years?

Most likely I’ll be a post-doc. Eventually I’d like to teach at the university level. My research interests will probably be completely different by then. From the graduate school interview weekends, I only got a sampling of the vast scope of research projects available. I could easily move from biochemistry to microbiology or synthetic biology. I haven’t even taken a genetics class or introductory neuroscience course, which are two subjects I am curious about. I have a feeling that whatever project I will be working on will be an integration of several different fields.

What advice would you give to potential graduate students?

Make note of general themes and broad questions that interest you. I wish I had started exploring scientific literature earlier, since you have access to all the major journals via Amherst.

Reviews are a great way to become familiar with new topics.

Also, experiments in research labs fail very often. Don’t take it personally. Furthermore, don’t be offended if your PI questions your thinking or work. There’s a lot to learn from these intimidating moments. If you don’t have these scary moments, then you’re not learning enough.

Feature

“I find it really fascinating how the human body and disease come into play in the medical profession.”

Akosua Korboe ’12 Akosua Korboe ’12 is a Neuroscience major from Ghana who was accepted into medical schools at Northwestern University and University of Rochester.

Why did you choose to apply to medical school?

I think I will find the most fulfillment as a doctor because people need human help to get back on track and on the path to recovery. I’m not the kind of person who wants to work in isolation. I’m currently doing a thesis and something missing in research is the direct link to people. A few years back, I was able to participate in a research program and although I enjoyed it, I realized that I would find medicine more fulfilling. I want to be helping the person sitting opposite me.

I have a good number of doctors in my family, so medicine was not a foreign thing to consider. Working at a hospital in Ghana also confirmed my interest in medicine. It was really cool and I thought “I can actually do this!”

It is more difficult for international students to be accepted into medical school in the United States. Did this affect your decision at all?

I had doubts was when I was deciding to come to Amherst simply because I was not sure about the feasibility of the process. When I started studying at Amherst, I was a bit worried that my plans to go to medical school would not work out as international students are not encouraged to apply. I really had to think about whether I wanted to go on this path and I asked myself, “Should I do it? Can I do it?” To be honest, I did not have a fall-back plan, but I had faith that admission process would work out. I believe passion shows through extracurriculars and interviews.

What advice would you give to international students planning to apply to medical school?

Medical school is possible but the kinds of schools you can apply to are limited. A good number of state schools won’t accept internationals. The main challenge is that your options are limited to only private medical schools which tend to be very selective. But I think schools appreciate seeing someone committed to medicine.

the fact that I am an international student. I want to fully use my capacity as a medical doctor to make a larger difference in the world, especially relating to issues at home (Ghana). I am not entirely sure about the specifics of how I am going to accomplish that and I actually do not expect myself to know this yet, but I am certain that, Godwilling, whether as a member of the WHO or an NGO, I will try to work towards this goal.

Why did you decide to do a thesis then?

I decided to write a thesis because of my interest in Neuroscience. I wanted to finish college with an independent study and prove to myself that I’ve learned this well.

Also I thought that having thesis work would be a plus to the application. Exploring dimensions of healthcare beyond the hospital is equally important, because it gives an insight into medicine that comes in handy when you’re applying. I wanted a broad array of experiences.

Any final comments?

I would advise underclassmen to be the best premeds they can be. I made sure I did the best I could to get decent grades in the classes I took here.

However, it’s also important not to become entrenched in grades. You have to put things in perspective. All aspects of how you present yourself count for medical school. Have time to enjoy your interests, which in the long run help you present yourself as a well-rounded student.

I tried as much as possible to engage in extracurricular activities I found enjoyable, as well as those that I knew would help me better discover my academic interests. For example, I sang in the Gospel Choir at Amherst and also joined GlobeMed to learn more about global health issues. Though medical school was on the back of my mind, the primary aim was always to find a balanced extracurricular life outside classes which I actually enjoyed.

Also, make friends with premed people--that’s how you get encouragement. Dean Aronson is a huge resource, and talking to the health professions committee can be beneficial as well.

Could you elaborate on your interest in global health?

As a doctor, I want to help countries beyond the country I’m working in. My interest in global health mainly stems from The Amherst Element, Vol 4, Issue 2. Spring 2012

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Faculty Interview

Interview with Professor Patrick Williamson Nguyen Ha ’13 Nguyen Ha ’13 sat down to chat with Patrick Williamson, Edward H. Harkness Professor of Biology, and reflect upon his journey to becoming a bioclogy professor at Amherst.

Nguyen (N): Why did you select biology as your career?

Prof. Williamson (W): I’m interested in many subjects.

Interest is cheap: the problem is putting time and effort into pursuing them. But I had lots of time when I was younger. As a kid, I was interested in cosmology. Cosmology led to physics, physics led to chemistry, chemistry led to biochemistry, and then to evolution. Then here I am.

N: That is so very interesting. Could you please elaborate on your intellectual growth?

W: I went to an experimental liberal arts college. They used to send students out as interns before being an intern became part of standard academic life. I interned at a biochemistry lab in Berkeley. A do-it-yourself person, I bought biochemistry textbook and read it. I applied to graduate school [Harvard University]. There, I studied as a biochemist but was also doing molecular biology.

In graduate school, I figured nobody cared about my grades. I certainly didn’t. They allowed students one year to take courses. First semester, I registered for four courses and audited four. The second semester, I took four courses and audited five.

I took both registered and audited courses equally seriously.

Meanwhile, I taught myself genetics. Then I became a postdoc [at National Institute of Health]. I had to commute 45 minutes on bus each way every day. I used that time to read, and got drawn into evolution. Later I ran into a guy from Williams who was teaching a comparative anatomy course at night. I ended up taking that course. We just got our hands on whatever we can find, chop it up, and studied it. It was all great fun.

N: What are your current research interests?

W: I am researching the mechanism via which a membrane enzyme controls lipid distribution across two bilayers of the cell membrane. [Readers interested in technical details can contact Professor Williamson in his office. He has cookies and exotic tea.]

N: What are some applications for this research?

W: I can make up a complicated enough answer that you will buy into it. But I will give you the honest answer: I don’t know. I will tell you a story. There is an old man up to his knees in the gutter looking for something. A kid asks, what are you looking for? Well, I’m looking for my key. Where did you lose your key? I lost it over there. The kid got confused and asked, but

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why are you looking over here then? The old man looks up and said, because that’s where the light is.

Not every particular research is related directly to some direct application, some cure for diseases, or etc. The cure for cancer is like the key in the dark. We researchers only look where the light is. One day, we might discover the key is in the dark twenty feet from where we are. But you have to start somewhere.

The same goes for my current research. Do I know if it contributes to an actual application? I don’t know. But someday someone might.

N: Wow, you were taking 8 -9 courses per semester and were still looking for more ways to learn? That is incredible. Also you moved from one scientific field to another quite often. How do you feel about taking risks? I mean, as undergraduates we have to mind our grades, but sometimes (or many times) our curiosity leads to taking risks. What advice would to give to students about balancing passion and grades?

W: Ah, let me tell you another story. There were two motorcycle racers. One racer was always faster than the other one.

One day, his fellow racer came and asked, “Why is it that you can go so fast? We have the same bike, the same wheel size, and same everything. If anything, my engine is better than yours.” The racer looked up at him and asked, “Well, have you ever fell down?” The fellow racer looked puzzled, and answered, “No, I haven’t.” The racer then shrugged and said, “That’s because you’re not going fast enough.”

In order to get somewhere, you have to go fast. To go fast, you have to be willing to fall down. If you’re worried about grades, you’re afraid of falling down.

N: [thinking] Right, I understand what you mean. If we go out of our comfort zones to follow our curiosity, and change fields like you did, we always run a risk. But you’re saying we must not be afraid, right?

W: Sounds good to me. However, about moving from field to field, I don’t think I was taking risks in the sense of putting things at stake where they were not at stake before. For example, there was as much risk in staying within chemistry as there was to go into biology. In that sense, I did not take any risk. I am not much of a risk taker. I am just curious in many things and I was young. On the other hand, the greatest risk I took was deciding to come here to Amherst.

Faculty Interview N: Could you tell us more about why coming to Amherst was a risk for you?

W: It is easier to transition from research to teaching, but it’s harder once you have taught for a long time to transition back into research. It is not impossible: it is just harder to go one way than the other. Resources and time are the two issues: once you’re entering a researching-teaching post, you devote a lot of your time to teaching.

But the literature and research world moves on. Besides, many institutions that focus on teaching have a lot less resources compared to major research institutions.

N: But you chose to teach and stayed at Amherst College.

What do you like about teaching?

W: Hm. Allow me to ask you a question?

N: Of course!

W: You’re studying at Amherst College. Why do you like being a student?

N: But professor…

W: [chuckle] Well I know: being a student is great! When you’re a student, things change every day. We’re like monkeys in that we like novelty. Being a student allows us to enjoy grand novelty for a long time. DNA, the central dogma, natural selection, physics, are large and powerful stuffs. It seemed crazy to us how much sense everything has to make. But somebody has to teach you those stuff.

Teaching is not asymmetric: teaching is as good as being taught, in the sense that when I teach my students teach me too. And I enjoyed being a student in this sense.

There is also another aspect. In 100 years we are all dead. We don’t want to be dead. But we will. How do you arrange it so that in 100 years, the fact that you were here made a difference? One answer, of course, is that you can teach. In 100 years, there are your students, and your students’ students. And they’re all so partly because you were here. Isn’t that neat?

N: That is such a great way to think about it.

I mean, really. I never thought of teaching that way. Besides science and teaching, what are your other interests, and how do they influence your scientific research?

W: I like politics, music, history, and poetry, but they don’t influence my research. Remember: it is in the nature of the sciences that your domain of investigation is intentionally limited. Science is about focusing on small field and on questions small enough to be answered once and for all.

That was also what partly drew me to the sciences.

N: Thank you so much, Professor Williamson!

*Photograph by Nguyen Ha ’13

Back cover photo: http://inspiringbetterlife.blogspot.com/2011/10/making-up-for-lost-time.html

N: What is your favorite Emily Dickinson poem?

W: “Alone and in a Circumstance.” Want me to recite it to you?

“Alone and in a Circumstance Reluctant to be told A spider on my reticence Assiduously crawled And so much more at Home than I Immediately grew I felt myself a visitor And hurriedly withdrew Revisiting my late abode With articles of claim I found it quietly assumed As a Gymnasium Where Tax asleep and Title off The inmates of the Air Perpetual presumption took As each were special Heir — If any strike me on the street I can return the Blow — If any take my property According to the Law The Statute is my Learned friend But what redress can be For an offense nor here nor there So not in Equity — That Larceny of time and mind That marrow of the Day By spider, or forbid it Lord That I should specify.”

Now, you might be wondering, who’s the narrator?

Pay attention to the beginning.

If you can’t figure it out, come back to me.