Duke University | Howard Hughes Undergraduate Program

When I first started this summer experience, I had no idea what to expect, and I was actually slightly worried because I had turned down Governor’s School in order to participate in Howard Hughes. I wasn’t completely sure if I had made the right choice or not, but now, looking back, I am so glad I made the choice I did. In the past, I have done other science summer programs, but this one was so different and new from anything I had ever experienced. Many other programs fret over the students and make sure they are taken care of during every waking hour. While that can be fun because one is constantly entertained, I had a blast being treated like a real adult, doing real research, in a real working environment. It is an opportunity that I wouldn’t give up for anything. There are less bows and ribbons and frills with the Howard Hughes Program, but that is what makes it so special. It is straightforward, cutting edge science, which we all get to see and experience first-hand as HIGH SCHOOLERS. Do you know how many people across America get a chance like this? I can tell you…..not many.

Unlike my PI, Dr. Allison Ashley-Koch, I do not know as a seventeen-year-old whether genetics will ultimately be the place for me, or even whether research at all will be. However, the experience of being in a lab has really opened my eyes to all the different possibilities science holds. Science is so much more than just pre-med students, as is the popular belief today. One of the main things that has truly opened my eyes to all the different paths that lay before me was all the lectures I heard throughout the course of the program. They ranged from drugs in the brain to songbirds to primate mating to alcohol and teenagers. The true width and breadth of science is astounding if one actually takes a moment to think about it. Walking into the Howard Hughes Precollege Program, I thought I was going to be a Chemistry major for sure. Now, however, after hearing multiple lectures about primates, evolution, and genetics, I think I am headed more for a major in Ecology, Environment, and Evolutionary Biology. That is one of the reasons I love this program. It is not simply a way to spend another summer or something that will look good on college applications, it actually has the power to change your beliefs, your perceptions, and where you actually go in life. It can make an impact.

As for me, after the Howard Hughes Program ends, my summer is practically over. Field Hockey (I am the varsity goalie) pre-season practice starts this coming Monday and I still have the bulk of my AP summer homework to complete before my senior year of high school begins on August 25th. Many people say not to worry about senior year, that it is a breeze compared to junior year, but I am more of the mindset of “I’ll believe it when I see it.” I know that this coming year is going to be difficult, so I have already started counting down the days until my free time basically disappears (wow, that is a very depressing thought!). On top of my difficult school schedule, I also have to worry about applying to colleges (as does every other senior in America). Currently, my top school is Columbia, in New York City, but these days it feels as though every week I have a new number one. I can’t wait to have our Howard Hughes reunion in the spring and see where everyone from the program is going to school. It is such a crazy idea that it is only months away; I can’t really believe it.

Before I sign off on my last blog, I do have some very important things to say. First, I want to say thank you to everyone who helped make the Howard Hughes Precollege Program possible, especially Deborah, Tanya, Kriti, and Chris. I know you all worked extremely hard this summer to make the program a meaningful experience for all of us, and I truly appreciate everything you have done. Second, I want to say thank you to everyone in my lab at the Center for Human Genetics, Allison, Karen, Melanie, Mike, Kaia, Heidi, and Megan. You all have been so helpful and accepting, especially when you were explaining concepts and procedures that I did not understand at all. Your patience has been invaluable, and my Howard Hughes summer would not have been the same without you. Thirdly, I want to tell everyone in the Howard Hughes Precollege Program with me that you guys are amazing, bright, talented people and I have had a blast hanging with you all for the past seven weeks. Finally, to those of you reading this who might be debating about participating in the Howard Hughes Program in a future summer, I say this: I don’t know who you are or what your situation is, but, for me, I am so glad I did the Howard Hughes Precollege Program because it is a fabulous, unparalleled experience that opens so many opportunities for the future, while one is having fun, learning a lot, and meeting exceptional people all at the same time!

~~~Helen
 

This blog was supposed to be about how my research is coming along; however, due to the fact that I am writing this slightly later, my research is actually completed. However, I can still talk about the ups and downs that I faced.

In general, my research went quite smoothly. For every SNP I used the same protocol, so towards the end, I actually became fast at completing SNPs. For example, when I first began I could only complete about three SNPs a day, doing then one-at-a-time. The last day, I completed eleven SNPs, doing them three-at-a-time. Its amazing how quickly one is able to pick things up. I was only in the lab for seven weeks, but the overall genotyping procedure became almost second nature.

One main complication I faced multiple times while doing research was that once I had made plates for a SNP, ran them in the PCR blocks, and scanned them, the analysis plot would look messy. This told me that something, at some point in the whole process, had gone wrong. Usually the problem was that the plate had amplified too much. Sadly, the only way to fix this problem is to make a whole new set of plates and run them on a completely different setting on the PCR blocks, and then scan them all over again. If the problem was that the DNA hadn’t amplified enough, the same plates could just be put back on the PCR blocks for more cycles; however, this was slightly worried me because there was always the risk of running them for too many cycles and then going from too little amplification to over amplification. Luckily, I only had to remake plates for two or three SNPs.

So, this was the main story of how my overall research went. After all the SNPs were genotyped, I only had one that had had an unfixable problem and had to be thrown out of the analysis. Once the statistician, Melanie, told me the results, I was happy. There had always been the chance that none of the SNPs would have an association with low birthweight or preterm birth. Luckily, though, some of mine did, so I actually had some pretty graphs to display on my poster.

~~~Helen

In my lab at the Center for Human Genetics under Dr. Ashley Allison Koch, life is quite crazy. I start my day by waking up at about 7:40, rushing through getting ready, to make it to the Howard Hughes classroom by 8:30. Once the group meeting is over, Claire and I take a ten minurte walk to get to our lab across campus. When I first get there, I usually have to put some Taqman plates, which I had made and put on the PCR blocks the day before, on the scanner. Each plate takes the scanner two minutes to run, and then there is some transition time between plates, so depending upon the number of plates I have to run, the scanner can take five to ten minutes or hours. While I wait for the scanner to finish, I usually head downstairs (my lab is actually on the third floor while the scanner and PCR blocks are on the fourth) and either make more plates for more SNPs (I can now make plates for three SNPs at a time) or I can analyze and submit data from plates that I had previously scanned.

Claire and I have about an hour for lunch if we want, so we usually meet with the Howard Hughes class at the LSRC (Levine Science Research Center) café called the Blue Express, go out to lunch with some people from the lab, or just eat packed lunches at the lab. Everyday is slightly different. The rest of the actual working time is spent juggling back-and-forth between making plates, putting them on the PCR blocks, waiting for the scanner to become free, waiting for plates to scan, and nalyzing and submitting data. Sometimes it can feel like a great deal of information to keep track of because every SNP seems to be at a different place in the process, however, as long as I keep current notes about each SNP, I haven’t seemed to have lost myself……………..yet.

Even though the whole process for one SNP is somewhat long and tedious, it is not that difficult. The actual difficult part comes if there is a problem with the plates made for a SNP. The problem only shows up at the end during the analyzing. Then, the problem has to be diagnosed and a solution has tobe thought of. Usually it involves going back to the beginning, re-making plates, and putting them on the PCR blocks at a higher temperature for fewer cycles to help the primers bond to the DNA better.
 

Among Dr. Ashley Allison-Koch’s many studies, I am in her Healthy Pregnancy, Healthy Baby Study (HPS for short). The overall goal of this study is to look at various SNPs (single nucelotide polymorphisms) in specific strands of DNA that encompass specific genes thought to affect low birth weight, preterm births, high maternal blood pressure, and preeclampsia. One of the reasons Dr. Allison Ashley-Koch first wanted to research this topic was because of its interdisciplinary nature. There are many racial disparities within the four effects in pregnancy being studied. The study was designed to look at possible affects to low birth weight, preeclampsia, etc from genetic, social, and environmental perspectives.

The specific part I play in this large study is in the genetic region. I am currently looking at thirty SNPs within inflammatory response genes on four chromosomes (1, 3, 4, and 5) and at eight different loci. The way I test the 30 SNPs are to go through a very tedious process in quite a repetitive manner. However, it never seems to get old. Everyday brings with it new challenges and a different schedule of events. The only part of the whole process I really don’t like is the analysis bit at the end. Well, now that I have told you this, you might be wondering what the whole process actually entails. So, here goes….

I start by getting out three Taqman plates, each with 384 wells with DNA at the bottom. I then make a mixture that includes distilled water, master mix, and a specific assay, which is customized for whichever SNP I am running at the time. Next, I use an electronic multi-channel pipetter to transfer the slightly lavender mixture into each of the total of 768 wells. This process is quite difficult because the wells are small and made of clear plastic while the pipetter is finicky and temperamental. However, once the pipetting is finished and a seal is placed on each plate, the plates are centifuged and placed in PCR blocks which control the polymerase chain reaction that amplifies the DNA.

Once the reaction is complete (which takes about two hours to run with an annealing temperature 60 for 50 cycles), the plates are centrifuged again and then placed on a scanner that reads the fluorescent dye that is found in each well. This part of the process can be very frustrating because the scanner machine also doubles as a Real-time PCR machine, which is used by many other labs and takes hours to perform. However, once the scanning is complete, the analysis must take place. The analysis part is up to my discretion alone and can be quite tedious when there are many plotted points that might or might not fit into an exact group on the plot. Once the analysis is complete, the worst part is over. The only remaining step is to submit the data to the database, so that it can be accessed at a late time by the statistician.

Well, that is the basis of my whole summer at the Center for Human Genetics. As complicated as it may sound, I am actually having a lot of fun, and I really like the work I am doing. One of my favorite parts is the fact that I can clearly relate all of my extremely detailed lab work with the bigger picture of how it affects the greater population and future knowledge.
 

~~~Helen

This week in my lab in the Center for Human Genetics, I had the opportunity to interview my totally awesome PI (principle investigator for those of you who do not know the lab lingo), Dr. Allison Ashley-Koch (pronounced Cook). Currently she is the head of numerous different studies, some funded and some not. Because the unfunded ones definitely move slower, more attention is paid to the funded ones, which include research on neural tube defects, attention deficit hyperactivity disorder (known more commonly as ADHD), sickle cell disease, and healthy pregnancy (which is the study I am in). It was really interesting to get to talk to Dr. Ashley-Koch in a more relaxed setting, to try and get to know the person behind the scientist.

When asked how she was able to arrive at the place she is now, Dr. Ashley-Koch delved into a long story about her entire science career. She went to the North Carolina School of Science and Math for her junior and senior years of high school. While there, she took a course completely on genetics and knew from then on that that was what she wanted to study and go into as a career. During eleventh grade, Dr. Ashley-Koch participated in a special projects week where she shadowed a number of people in the genetics field at Duke University. She kept up these newfound contacts and during her senior year, she worked with a geneticist one afternoon per week for course credit. As an undergraduate, Dr. Ashley-Koch attended the University of North Carolina at Chapel Hill, but she kept in contact with the geneticists from Duke. College forced her to start narrowing down what kind of genetics she wanted to focus on. One thing she did know was that she did not want to work in the drosophila labs. She said that whenever she had to work in them for class, she would find dead flies all over her clothes and would come out smelling like molasses. Towards the end of her four years at UNC-CH, as she looked toward graduate school, she faced the difficult decision of whether to go into clinical genetics or epidemiological genetics. In graduate school at Emory University in Atlanta, Georgia, she decided to focus on epidemiological genetics within the angle of math and statistics. She did her dissertation on Fragile X Syndrome, while at Emory, and came out with a Ph.D. After Emory, where she met her future husband, she did a post-doc for one year at the Center for Disease Control in Atlanta, and then moved to Duke University to finish her post-doc (for another two-and-a-half years) working under her old high school mentor. At Duke, she worked in the Center for Human Genetics (CHG) with a focus on autism and did a little with neuromuscular conditions and sickle cell disease. After her post-doc, she continued to work at the CHG under Marcy Speer. When Dr. Speer died of cancer two years ago, Dr. Ashley-Koch took on her studies in addition to her own. She still works at the CHG.

After this long question, I asked Dr. Ashley-Koch what her favorite project is. She responded by saying that all of the projects she has worked on have been like her children. It is difficult for her to choose just one because they are each different in their own ways and each has its own pros and cons. However, she did say that the Healthy Pregnancy Study is one of the most interesting to her because it is very interdisciplinary, combining social, environmental, and genetic variables and correlating them with diseases using statistics.

When asked, Dr. Ashley-Koch said the most difficult part of her job is dealing with the things that are not taught or discussed in graduate school, things like managing budgets, writing grants, supervising people, and working with people who do not take constructive criticism well.

If she wasn’t working as a Principle Investigator at the Center for Human Genetics, Dr. Ashley-Koch said she would probably be a pediatrician or an elementary or middle school science teacher.

During her free time, Dr. Ashley-Koch likes to play with her two sons, Nathan who is seven and Justin who is four. They are involved in many activities like sports and music. In addition, she does normal household jobs like the laundry and cleaning, she goes out with her friends, and she likes to listen to music with her husband who plays drums in a hard rock band.

When asked what advice she would give to students who are trying to figure out what career is for them, Dr. Ashley-Koch said that she was the outlier. She knew that genetics was her thing since the middle of high school, but most people have no idea what they want to do until the middle of college or even later. She recommended getting exposure to a bunch of different areas and careers, whether it be through shadowing professionals, volunteering, or participating in summer programs.

Some of the craziest lab mistakes that she has made are that she messed up which electrode went on which end of a gel electrophoresis, caused a radioactive spill, and started an ethanol fire.

Dr. Ashley-Koch also said that she never really gets bored with her career. There are times when she gets mentally stuck, but she never really wishes she was doing something else. She likes her job and the science she is studying way too much!

Well, that is my PI, Dr, Allison Ashley-Koch in a nutshell. I feel like I know her much better as an ordinary person. Also, I feel much less intimidated by the lab, now, because I know that any mistakes I make won’t be nearly as bad as starting an ethanol fire or causing a radioactive spill!

~Helen