Author Archives: Claire Yin

As May turned to June and I found myself on a flight back to Durham, I was nervous, apprehensive, excited, curious. I wasn’t sure what to expect–how I’d get along with the other students in the program, if I would fit in well with the lab, if I would be happy with what I was doing over the summer.

I remember coming into this program with the hopes that it would help me narrow down my list of possible career choices for the future. It did, in the sense that I got to experience a few weeks of being a researcher and had invaluable conversations with people hoping to become a Ph.D., people well on their way to earning one, and people who are already established figures in their field. There was a lot about a career in research that I wasn’t really aware of, and thus a lot that I got to learn about in these past eight weeks. I can’t say for sure that I now know exactly what I want, but I’m really thankful for having had this opportunity.

This summer came with its obstacles–there were nerves in the beginning, mistakes made, failed experiments. Though many had warned me going into this, including Dr. Grunwald, I was still caught off guard by these setbacks. Research is all about discovery, of course, but being so used to academics, where everything already has its own right or wrong answer, tackling the unknown had felt almost like blind grasps at nothing. Not being able to determine exactly what went wrong in our experiments, what to improve for the future, whether it was me making mistakes or possibly faulty materials or reagents–I was overwhelmed by the uncertainty of research. 

But the beauty of research, and what I got to experience a little by the end of my eight weeks, comes with perseverance, embodied in the moment that ignorance turns to enlightenment. After your efforts pay off and you get results, seeing data that confirm your hypothesis or show you something novel or unexpected, these moments–of the euphoria of discovery, and the words of congratulations from your mentor or the surprise on your PI’s face when you inform him of your possible findings–dull every negative thought you might have once had. I’m relieved to have found myself really enjoying my first research experience, through all of its ups and downs, in a way I always hoped I would.

Looking back on my first blog post, I had a lot of other expectations, many of which might have been a little ambitious for just eight weeks. But I’m looking forward to checking off those boxes one by one as I continue my research in the McClay Lab into the upcoming year. 

A big thanks to Dr. McClay, my mentor Esther, and Michael, as well as the rest of the lab, for being so helpful, patient, and welcoming this summer. Thank you, Dr. G and Anna, for the wonderful eight weeks of learning, working, and evolving. On Saturday, I’ll be heading home with a new mindset and greater clarity, coming away from Durham a little wiser and looking forward to the new semester and journeys ahead.

As a veteran scientist and Nobel laureate, Dr. Robert J. Lefkowitz had much to share to our group of budding researchers when he came in for a faculty talk a few weeks ago. Heading into our sophomore year, we are intimidated by the looming expectations of choosing our majors, of deciding on a career path that we hope to love. We are burdened by worries, by questions that weigh on our minds that ask if we’ll be happy doing the same work years down the line, if the decision we make will be the right one. These concerns are experienced by everyone at a certain stage in their life, but as valid as they are, Dr. Lefkowitz assures us that there is little they will do to help when the world, or fate, or in his words, “serendipity,”–however you’d like to call it–steps in to take charge. 

Growing up, Dr. Lefkowitz idolized his family physician and was sure he wanted to be a doctor. He went through high school and his undergraduate years doing no research, dead set on heading straight towards medical school and afterwards, residency. But in order to avoid being drafted into the war, he applied and was accepted for a position with the NIH in the U.S. Public Health Service. He wasn’t particularly interested in research at the time, and the initial failure he experienced at the institute worsened his dismay. But as time passed and his project began to come together and succeed, his perspective changed and he was drawn further into the thrill of discovery. He would gradually spend less and less time in the clinic, dedicating more of his efforts in the lab. Eventually, he would transition almost fully towards just research. 

“There is serendipity in science,” Lefkowitz states slowly, contemplative. He says this in reference to his discoveries in the lab, as well as that of his past colleagues at the NIH, who collectively have earned nine Nobel prizes. 

But there’s more meaning behind that, I think. So sure that he was meant to become a physician, so much that he never touched research until it was absolutely necessary, it was a series of life events he had little control over that led him to the NIH and to stay there. Dr. Lefkowitz’s time in research and the moments in his life that led him to learn to love the field, all contributed to his discovering his ultimate passion. I’m a firm believer–as I think Dr. Lefkowitz may be as well–in the idea that, no matter how much you might agonize over your future now, life will eventually lead you to where you’re supposed to be.

Brachyury is a transcription factor that has been determined to be an essential component in the course of sea urchin embryonic development. We know that it is expressed at both the blastopore and stomodael opening of the embryo, but inactivates in cells that leave those respective areas. Additionally, in its absence gastrulation does not occur. What makes this protein so integral to these morphogenetic movements, however, remains a mystery. We hope to find an answer to this question by examining how brachyury plays a role in gene transcription and protein synthesis. In this study, we will be investigating a number of genes known to be associated with the formative stage of gastrulation and analyzing the change in their expression with brachyury both present and knocked down. Through in-situ hybridization, we will observe the location and expression patterns of each gene in regards to the presence of brachyury, and use that information to draw associations. We hope to eventually generate a detailed and extensive gene regulatory network on the brachyury gene in order to establish a deeper understanding of the processes that prompt its behavior. 

The chalk talks we presented and listened to earlier this week were all really interesting, and everyone did a wonderful job of explaining what projects they’re working on this summer. But Michael’s chalk talk especially stood out to me, because while many of the projects, including mine, were mainly stuck on the primary stages of looking into and understanding certain processes before thinking about application, I thought Michael’s project on pain seemed to be a few steps ahead, being more developed in the sense that it is founded on well-researched principles and also has direct applications in health and medicine.

Michael’s project is centered around the STING protein, which is believed to be important in the regulation of pain and the immune system. Because STING is naturally found in the body to activate interferons, reducing neuroinflammation, and thus pain, his lab believes that increasing the amount of STING protein in the body could throw a wrench in the vicious cycle of chronic pain and possibly make strides towards discovering an effective solution to both cancer and the opioid crisis.

Michael’s experiments include poking mice with filaments that exert different levels of force in order to observe their response and tolerance to pain. His job will be to locate the exact threshold at which the mice are able to sense their own pain, but he is also working on eliminating other possible factors that might contribute to an increased pain response, of which includes anxiety, which will eventually allow for a clearer and more solid conclusion.

There’s still a lot to discover about the mechanisms and logistics behind STING, of course. But their project is built upon previous research that seems quite promising. Michael’s research is fascinating, and will be monumental if the results turn out positive. If we can control pain, without that leading to more and more problems, the world of injury and healing could change dramatically. But at this early stage, I wonder about long-term effects (which they are looking into at the Ji lab as well), practicality, and even future avenues: could pain eventually become something that can be eliminated entirely? And if so, should it be?

Either way, I loved hearing Michael’s chalk talk, which he presented in an engaging and articulate manner, and enjoyed having the chance to view pain from a perspective I’ve never thought to consider before. I’d always thought of pain as an essential part of being human, a warning sign to injury. But maybe, this relationship isn’t so clear cut. Maybe there’s something to discover that we never could have imagined.

And isn’t that what research is all about, anyway?

As an undergraduate, Dr. David McClay was a man of many interests, curious and adventurous and carefree. He was fascinated by all that his school had to offer him, and spent his four years at Penn State exploring anthropology, philosophy, and a number of other majors before eventually settling with biology. Despite growing up knowing that he wanted to be a professor like his father, Dr. McClay was content with living life day-by-day, relishing each moment in its present.

When he went on to graduate school at the University of Vermont, a decision he made rather spontaneously after encouragement from his father, Dr. McClay was still rather unhurried about his future. But in the time he spent there, enjoying the serenity of the mountains and taking time alone in his thoughts, he began to ponder. He wondered about life later on, the kind of person he wanted to be, the things he wanted to do, who he wanted to love. These years were integral to his growth and maturity. By the end, he had come up with three things.

1. He knew he wanted to be successful.
2. He was willing to work hard for it.
3. He was going to love it.

He later went on to earn his PhD at UNC, and spent his postdoctoral fellowship at the University of Chicago. These years eventually led him to Duke, where he has been since.

When asked about his favorite part of working in research, Dr. McClay told me that he loved to reduce questions down to ask how the little, smaller processes work. He enjoyed the creativity that comes with his research, as well. But the thing that is the most rewarding to him, he says, “is the illumination in the eyes of students when they get it.” As a professor and mentor, he is a key figure in introducing students to research, guiding them along the path of discovery. To witness as something in them clicks, as the project they’ve been working on for months or even years falls into place, to see that joy and excitement is, he tells me, his favorite part about doing what he does.

One of his favorite moments in the lab, however, is a discovery of his own. In the 1970s, after the emergence of monoclonal antibodies, he was the first to find markers for individual cell types. This marked his entry into the field, as he presented his results at a meeting for sea urchin researchers. The audience was stunned by his brilliant and colorful images; red and blue and green illuminated each component of the sea urchin embryo “just like a Christmas tree,” Dr. McClay recounts, eyes bright and animated.

Those vivid memories of the feeling of success, of hard work finally paying off, and of recognition still bring tears to his eyes. But despite that, his journey–as did everyone’s–has had its bumps and bruises. He remembers one time that stood out from the others, when he so believed in his hypothesis that he refused to acknowledge the data he gathered suggesting otherwise. He hadn’t realized at the time, but that experience allowed him to understand that the most principal goal in research is having a correct outcome, not to prove your own hypothesis. To overcome mentalities like the one he struggled with, he offers a simple, yet significant piece of advice to me, and to others in my position:

“You have to learn to reduce your fear of failing. It’s okay if you are wrong.”

On his own time, Dr. McClay continues to be a man of many interests. He enjoys tending to his flower garden, biking, reading, skiing and traveling, among other things. He has mastered how to balance his priorities between loved ones, pleasure, and work, all of which are equally as important to him. Over the years, he has had to fight his own ego, learn to embrace difficult truths, and power forward into frightening new beginnings. He has since found success, he has worked hard for it, and he has loved every moment of it.

As high school biology teachers often remind us, we’re more closely related to other animals than we might generally like to think. We all eventually, when traced back far enough, stem from a single ancestor. And despite our distinct and innumerable differences, just a few, significant similarities are enough for such blasphemy to begin to station in truth. One of these, found in all bilateral animals, and the subject of my investigation for the following weeks, is the presence of the transcription factor, brachyury.

In an embryo, specifically of deuterostomes like humans, the first feature to develop is the anus. The embryo then invaginates at the anus—turning itself inward—and gradually stretches towards the mouth at the other end of the embryo to form an early version of the gastrointestinal tract in a process known as gastrulation. We know that brachyury plays a critical role in this stage of embryo development, though much about the protein remains an enigma. We know where brachyury is expressed, though we do not know what processes it controls; we know that it’s presence is essential for proper development, though we do not know why that is and what causes the failures observed in its absence. My project at the McClay Lab will be to examine further these characteristic of brachyury and its role in gastrulation, to seek answers to the many questions surrounding this crucial protein, yet shrouded in mystery.

These past two weeks have been dedicated towards locating brachyury in embryos undergoing gastrulation. Knowing where it is, how it is expressed, and at which stages one may observe each pattern of expression will be the first step I take towards learning more about it. We hope that this investigation will eventually lead to a deeper understanding of gastrulation and embryo development as a whole, and unlock some of the many secrets to the complexity of our being.

This is new to me. Everything here. My first research experience has been a whirlwind of pipetting and centrifuging and following protocol this past week–a routine of mundane tasks in the lab that, to me, have yet to seem so familiar. Walking into the lab every morning, I am a mix of feelings of curiosity and intimidation and excitement. The novelty makes it all a little frightening, and I’m not sure if I’m more scared or excited each day. But there’s something comforting in the work I’ve done so far in the lab. I enjoy how concrete it is. How grounded. Everything I do, I’m doing for a reason. Each step I take acts like little puzzle pieces that slowly, gradually, with effort and dedication, come together to form a bold and beautiful picture. 

This summer, I plan to leave this experience without regrets. I want to learn what it means to be a researcher. I want to be unafraid of asking questions, no matter how silly they may seem. I want to understand and contribute to our work, to come out of it feeling not as though I was temporary, but rather that I’d become an important part of the lab. I hope to build deep connections and lasting relationships with the members of the lab, and that I’ll be able to continue with them in the fall if all turns out well. Maybe, I might even be able to help discover something unheard of before. 

But overall, I’m looking forward to coming out of this experience with a greater knowledge of who I am and who I want to be. At the end of these eight weeks, being immersed in a snapshot of a life centered around research, I may realize this as the setting in which I belong or, on the other hand, where I don’t want to be. I might find new interests that will inspire me, or aversions that will deter me. I might draw new possibilities for myself, a blend of what I’ve wanted in the past and what I will have come to want afterwards. This summer will be dedicated to understanding the kind of things that I want to do, and the topics I am passionate about. Before now, without the proper experience, I’ve been blindly grasping at possibilities I think might stick. With BSURF, I’m excited to have the opportunity to truly get to know this part of me better. This summer may not turn out exactly as I hope but I’ll be grateful for it anyway, because whatever my experience will be–good or bad–it will have still have brought me that much closer.