Author Archives: Alissa Kong

The End of a New Beginning

This summer has been a great learning experience, both in terms of making me more aware of the science community here at Duke as well as helping me develop skills to become a better scientist. I got the opportunity to meet so many amazing people and hear about the exciting research projects they started this summer. The faculty talks exposed me to a wide variety of research topics and made me realize how so much is still unknown about the world. Beyond just learning about science and research, I also developed skills that will be useful during my remaining 3 years at Duke, as well as further into my educational career. I learned how to effectively read and understand the main points of scientific journal articles, and perhaps more importantly, I learned how to communicate my own science, whether it be by presenting a chalk talk, creating a concise abstract, or making a poster to present my findings.

These past 8 weeks in lab has definitely taught me a lot about science in general and how the whole process of research involves a multitude of steps beyond just running an experimental trial. I realized that steps such as doing preliminary testing, planning an experiment, training animals, conducting control trials, collecting data, processing data, and analyzing that data are just as important as the experimental trial in exploring a research question.

Although this summer’s research experience has not greatly influenced my future career choice, it has showed me what one can do with a background in biomedical engineering and how the science we read about can be applied in a laboratory environment. Attending lab meetings and reading journal club articles gave me a better understanding of what biomedical engineering in a neurobiology context means and how we can use various optogenetic methods to explore novel ideas about the brain.

Reflecting on everything that I was lucky enough to experience and accomplish this summer has made me beyond grateful for the BSURF program. Although BSURF has come to an end, I look forward to continuing my journey in the science world!

Science is Everywhere

Over the past couple of weeks, we’ve had the opportunity to listen to a variety of scientists speak to us about the amazing research they have been working on in their labs and how they got to where they are today. Hearing about the different paths these faculty took to end up in the same research institution made me realize that everyone has his or her own way to approach opportunities and explore interests. In addition, learning more about all the kinds of research these faculty have been involved in highlighted the endless possibilities of science and how so much is still unknown about life in and around us.

Out of all of the faculty talks, Dr. Lawrence David’s talk about nutrition really resonated with me because it made me realize that is that science really is everywhere around us: in the movies we watch, the foods we eat, and the places we visit. He mentioned that watching Jurassic Park was what initially interested him in scientific research. Who would have guessed that a night out to the movie theater would result in finding a new interest and passion that you pursue as a career? 

Dr. David’s lab focuses on nutrition and how the different foods people eat affects their bodies at the microbiome level. While not everyone consciously monitors their diet every day, nutrition is a concept that is relevant to everyone. Research like this that has such a direct and immediate connection to our everyday lives really makes clear the importance of science and how it can appear anywhere. One really memorable part of Dr. David’s talk is when he mentioned the time he visited Thailand. Although the trip was not originally for work purposes, he tracked the street food that he ate and monitored how this new kind of cuisine affected his body. He brought his research and scientific curiosity with him and created a new learning opportunity for himself. As I continue to explore the different aspects of scientific research, I hope to embrace the unknowns of the scientific world and am excited to see where else science may unexpectedly present itself in my daily life.

Abstract

Place cells are a type of pyramidal neurons in the hippocampus that activate in a pattern that encodes for space as an animal moves through its environment. Our current project examines how the brain reacts to unexpected visual manipulations by looking at place cell activity. We hypothesize that the greater the visual spatial manipulation, the greater the place cell activity will deviate from normal activity. A genetically encoded indicator recorded neural activity in the mouse’s brain by binding to calcium ions and fluorescing. An algorithm called constrained non-negative matrix factorization identified areas of fluorescence that may represent neurons, but also generated many false positives. Eliminating these false positives is necessary for a more accurate analysis of place cell activity. The percentage of false positives will also allow us to reexamine the effectiveness of the algorithm and identify areas of improvement to generate more accurate neuron selections. By analyzing only the neurons that represent place cells, we hope to better understand how the brain uses vision and how vision is being used to correct for errors. In particular, these findings may have significant impact in disease models, such as Alzheimer’s research, in which the patients have difficulty with episodic memory.

A Day of Neurons

A typical day for me in the Gong Lab consists of me helping my mentor, Emily, with her project on how visual manipulations in virtual reality affect the firing pattern of place cells in mice. This project has been ongoing for a couple of months, and the data collection of the mice running through different conditions in the virtual reality set-up has already been completed.

What I am doing now is selecting through a list of computer generated masks and determining which circled areas are neurons and which are just arbitrary areas of fluorescence. This is necessary because the algorithm that is used to circle the potential neurons is not always accurate and may outline a group of pixels that does not represent a singular neuron. For example, the outline might circle two neurons, the space between two neurons, only part of the neuron, part of a neighboring neuron, etc. What I have learned from this particular task is that science is a slow process and that while looking at neurons firing on a computer screen may seem like a repetitive and mundane job, it is just as important towards the final results as any other step in the research project. 

Additionally, Emily is starting to train new mice, so I am getting some more hands-on experience with the mice and with the wet lab aspect of research by helping with the water restriction process. This process consists of giving a small amount of water to each mouse only once a day and recording the mouse’s percent weight loss. This water restriction process is necessary because in the experimental and training period, the mice are given water as positive reinforcement to reward their behavior.

In my free time at the lab, I am also working on improving my MatLab skills by practicing with some problem sets. These problems focus on the areas of MatLab that are important for the coding of the video processing program that we are currently using to select through the potential neurons. Once I have mastered the MatLab skills in these specific areas, I will be able to better understand how the computer is generating the masks around the areas of fluorescence and hopefully be able to use this deeper understanding to make more accurate neuron selections.

Curious About Learning How Curiosity Affects Learning

When I was younger, I remember wondering about why things are the way they are. Like why is the sky blue? What causes the seasons? Why does it only snow when it’s cold outside? The world is full of so many unknowns, and curiosity is the driving factor that leads to discoveries about these unknowns. But something that Eleanor’s chalk talk made me realize was that curiosity is more than just asking deep questions about the world. By simply going through day to day life, humans are constantly curious and learning about the world around us, whether or not we are consciously aware of it.

Eleanor’s project is focused on exploring the relationship between engagement, curiosity, and memory through showing human participants art videos that gradually take the form of a recognizable object. As the video progresses and more information is given to the participant, engagement is varied by controlling when and what the participants are allowed to guess regarding the identity of the drawing shown. These differing levels of engagement are then hypothesized to result in different levels of self-reported curiosity. By testing the memories of the participants the next day, the researchers will be able to better understand the relationship between engagement and curiosity and how that relates to learning and memory in participants with varying personality traits.

I am excited to see how the factors of engagement and curiosity apply in an educational environment and what that means for students and teachers. I thought that the experimental-set up was really interesting because I feel like sometimes in classes, the teacher is telling you exactly what the answer is instead of allowing you to come to the answer by yourself at your own pace. Going off the hypothesis that the least engaged group of people will have the lowest levels of self-reported curiosity, it would be interesting to see how this correlates to in-classroom teaching methods. For example, would this be similar to a lecture-style class with the teacher telling the students exactly what the facts are and how to answer certain types of questions? 

I feel like a lot of what we are being taught in class is for the sake of learning what we need to know to do well on exams and get a good grade. Finding the best methods of teaching for each type of student can help get students genuinely interested in what they are learning. This would be a big step in improving the methods of teaching and making learning a more enjoyable and worthwhile experience for both students and teachers alike.

Discovering Science with Dr. Gong

Dr. Yiyang Gong is the Primary Investigator of the Gong Lab in the Biomedical Engineering Department at Duke. He has always had an interest in the growth and learning aspects of science and believes that applying science to address interesting problems through research is a big part of the field. He completed his undergraduate degree at Cal Tech and went to Stanford for graduate school and his postdoctoral fellowship. Dr. Gong majored in electrical engineering, which he finds useful as the biomedical engineering department here at Duke draws a lot from EE. In grad school, Dr. Gong focused on applying nanophotonics to record novel things in the brain by looking at how nanometer-scale objects interact with light. For his post-doc, Dr. Gong delved into protein engineering and was interested in light sensors that respond to neural activity. These sensors look more at action potentials rather than calcium transients, thus giving more precise temporal estimates of brain activity. Through his studies, Dr. Gong applied the quantitative skills he had, like math, statistics, and optical design, to something that can be solved with biology while advancing science along the way.

After his post-doc, Dr. Gong was excited to bring his research topics together to discover new phenomenon about the brain. By using both optics and protein concepts to develop and apply new optical tools that can look at the brain in more detail along certain dimensions, Dr. Gong was able to carry out new types of experiments that he would otherwise be unable to do.

Dr. Gong’s daily life includes guiding people in his lab with their experiments, teaching undergraduate and graduate courses, and writing applications and drafts of papers. Dr. Gong’s favorite part of his job is learning new things, both in teaching and in research. In the Bioelectricity and Optogenetic Tools courses he teaches, he finds that teaching a concept by giving new examples sometimes gives him a better understanding of the model and creates a new perspective with which to view an idea. In the lab, he finds that there are small opportunities to learn every day. By accomplishing a set of tasks, he is able to discover something about how to do an experiment, what techniques work, what doesn’t work, etc.

In terms of science in general, Dr. Gong believes that science is its own process and that although it is often unpredictable, things will come in time. While there isn’t anything major that he would change about doing science, he would like for science to be more exploratory and less monetary-based. Currently, a lot of what he does in the lab and thinks is true for science in general is that research is largely driven by business. In an ideal world, he would like for science to have less of a business environment and be more about discovery.

Some big-picture advice Dr. Gong would give to students and people trying to figure out their future is that you should do what excites you. It’s less about what you want to do, but more about the fulfillment you want to experience in a career and what kind of impact you want to make through your work. I plan on taking that advice with me as I start finding my way through this summer of research, the rest of my college years, and beyond.

What Do You Remember About Virtual Reality?

This summer, I am working in Dr. Gong’s Biomedical Engineering research lab on a project focused on examining place cells in the hippocampus of mice. Place cells play an important role in spatial and episodic memories and the current project looks at how visual spatial manipulations affect how place cells are fired.

A 1-photon microscope was used to record the firing of the neurons. First, an Adeno-associated virus that carries the protein GCaMP6f was injected in the hippocampus of the mice. This particular virus was selected because GCaMP6f has a unique ability to bind to calcium ions and fluoresce. As a result, when the concentration of calcium is high, more of the GCaMP6f is bound to Ca2+, resulting in increased fluorescence that can be picked up by the 1-photon microscope. Since Ca2+ increases during an action potential, we can correlate the increases in fluorescence to periods of neural activity.

The physical experimental set-up consisted of a styrofoam cylinder that served as a linear treadmill, on top of which the mouse was placed. A virtual reality display was shown on monitors in front of the treadmill and the mouse controlled its movements in the virtual reality through its actions on the wheel. The purpose of the virtual reality was to allow for manipulation of what the mouse sees in ways that couldn’t happen outside of a computer screen. After a training period, the mice ran through randomized trials that consisted of either running on an unaltered track or on a track with a visual spatial manipulation.

After running the experimental trials, an algorithm called constrained non-negative matrix factorization was used to identify areas of fluorescence that may represent neurons. However, the computer is not always accurate and may outline a group of pixels that are not neurons. For example, the outline might circle two neurons, the space between two neurons, only part of the neuron, or part of a neighboring neuron. Currently, my primary job is to identify whether the computer-generated outlines are actually neurons or not. To do this, I pay attention to nearby pixels that brighten and dim together. If the outline encapsulates a group of pixels that fulfill those criteria, then it is most likely a neuron and I select it.

After all this data is processed, we will be able to identify place cells and determine their function by correlating their respective calcium transients to locations in space. With this information, we will be able to better understand how place cells react to visual manipulations. This information will be useful in looking at how vision corrects for errors, in better understanding how the brain uses vision, and in further understanding how the brain works in general, allowing future researchers to compare this data to disease models.

A special thanks to my mentor Emily Redington for her help with this blog post!

The (Action) Potential of Research

Coming into B-SURF, I had very limited experience working in labs outside of the structured step-by-step procedures I followed in the lab section of my science courses. I was even less familiar with the research and the process behind the countless scientific discoveries that appear in the news. I expect that spending these 8 weeks with the B-SURF program will give me the new and exciting experience of working in a research lab and familiarizing myself with all that goes on in carrying out a formal experiment. I hope to have a better understanding of the bridge between the science we learn about in class and the ground-breaking discoveries we see in the headlines. I hope to get to know what happens behind the scenes by not only listening to what my peers are doing in their labs and observing others conduct experiments, but also by answering scientific questions myself.

I expect that I won’t understand everything that is going on in the lab at first glance and that I will be confused and make many mistakes. But I also expect to be okay with making mistakes, own up to them, and transform them into learning experiences. I expect to work deliberately to keep an open line of communication with my graduate student mentor and PI in order to make our collaboration a meaningful one. In particular, I hope to ask a lot of questions and really make sure I understand the purpose of the experiment that I will be contributing to and where my work will fit into the broader research project. I want to learn about all aspects of the research community, ranging from the inspiration of the experiment to the equipment used in collecting the data to the process of publishing a paper.

While I expect to learn a lot of new concepts, techniques, and skills in lab, I also expect to learn a lot outside of lab, through the people I meet and the stories we share. I hope to meet many new people, both in the B-SURF program as well as in the lab, and form meaningful and lasting relationships with them. I hope to have exciting, mind-opening conversations about the work we are doing and listen to the stories and motivations behind their work. I expect to create these connections over the course of this summer, and I hope to keep the relationships going even after we leave and go our separate ways.

Picture in front of my lab building