Dr. Ru-Rong Ji: Chief of Pain Research

You know how a lot of the times when you look at someone very successful you imagine that they must have always known what they wanted to do, had a detailed plan of how they were going to do it, and simply did it. Well recently I have been realizing that in reality, this isn’t how the narrative goes, and I was able to see this yet again through mi PI’s story. Dr. Ru-Rong Ji never initially imagined there was a possibility of him going to college. Being from China in a time where there was a lot of political turmoil, he says it was not part of his foreseeable future until Deng Xiaoping opened the country to the rest of the world and the US said that they would allow half a million Chinese students to come study in the states. Dr. Ji earned a bachelor’s degree in biology in China and did research on acupuncture analgesia with a professor in acupuncture for 2 years. This marked the beginning of his interest in pain and neuroscience research, which later led him to get his Ph.D. in neuroscience in Shanghai. Continuing his academic career, Dr. Ji went to Johns Hopkins as a Neuroscience fellow in the school of medicine for 3 years, spent 2 years in Stockholm studying gene regeneration in animal models, and then went to Harvard Medical school which he considers was a turning point in his career as he took on the role of Instructor and got his first NIH funding. After a total of 14 years there he came to Duke, has been here for 10 years, and is currently the chief of pain research. 

Despite not initially picturing his future to evolve into what it has, it is what he now considers to be his dream job. One of the things he enjoys most about it is the new discoveries you can make when doing research, always new and exciting projects, and how creative the job requires you to be. Not to mention the amount of traveling he has been able to do as part of business trips and the like. He says you get to see the world and often be shown around the area by colleagues. Although working in the lab can involve many hours per week, he also enjoys the flexibility that also comes with it.  

It has been so wonderful seeing how much his research means to him and his dedication towards it. From what I can tell, Dr. Ji is also always attentive to the people in his lab and comes in to check on things in the bench lab area at least once a day. A healthy lifestyle and good mentality are things he considers have helped him also get where he is today and says that he sees himself continuing with his research for many more years to come. With this in mind, there are a few key things he considers critically important for being successful which include having a good attitude, being patient, and being persistent. These are things I will keep in mind as I embark on my own career journey and use Dr. Ru-Rong Ji as an exceptional role model in the field that I am profoundly interested in.

Dr. Stacy Horner’s Journey in Biology

The principal investigator in the Horner lab, Dr. Stacy Horner, is the co-director of the Duke Center for RNA Biology and an associate professor of medicine and of molecular genetics and microbiology at Duke, having opened her lab at the university in the 2013-2014 academic year. I have been working in her lab for about a month now, with multiple opportunities to get to know her better and learn more about her journey into the world of microbiology and host-virus interactions, as well as how she got to her current position. Recently I was able to meet with her to talk about this journey to where she is now.  

She grew up in Minnesota, where she first found a general interest in biology and chemistry in school but knew little of the research opportunities in these fields. As she searched for colleges that would enable her to explore her interests in biology and chemistry, she ended up attending Gustavus Adolphus College. She said she wanted to choose this school because it was a small liberal arts college in Minnesota that enabled her to explore both biology and chemistry with a biochemistry major. Going into college, she said that she knew very little about the world of research. She was able to dive into research through her undergraduate classes but did not consider going to graduate school in a PhD program until later in her undergraduate career as she learned that unlike other degrees, many PhD programs in the sciences do not require one to pay tuition and instead pay the students. Through this knowledge and encouragement in undergrad, she began to pursue graduate school for a PhD program in molecular biology. 

She joined the lab of Dr. Daniel DiMaio at Yale University, where she began to research human papillomaviruses. Throughout her time in graduate school, she did not believe that she would become a professor or principal investigator in a lab in the future. Dr. Horner said that she thought that she might not be creative or capable enough to constantly come up with the questions and ideas for a lab. It was when she was talking with mentors about her plans for the future that her mind was changed. When she told her mentors that she would not pursue postdoctoral studies and a professorship because of these reasons, they said that they thought she did have the skills to pursue the path to professorship. It was with their encouragement that she decided to pursue postdoctoral work. 

In her postdoctoral work, Dr. Horner studied the regulation of the innate immune system concerning Hepatitis C in the lab of Dr. Michael Gale at the University of Washington. She then opened her lab in the Duke school of medicine where she currently pursues research in RNA virus host interactions, often concerning the innate immune system and Hepatitis C. Stacy has been incredibly welcoming, knowledgeable, and enthusiastic as I have gotten to know her in joining her lab. I am very excited to talk more and learn more with her in lab! 

Dr. Ke Dong: From Silkworms to Toxicology

At the Dong Lab, the principal investigator Ke Dong has had an interesting journey through her studies and research. While interviewing her this week, I learned more about how she became interested in her field of science and research. She recently moved from Michigan State University to Duke, so we also spoke about that transition and what her long-term goals for her lab are. Dr. Dong is an excellent person to talk to about how to take your life long or childhood passions and turn them into a career.

**I have paraphrased her answers to keep this post concise and focused on the key elements of her responses.

Q: Where did you do your undergraduate and graduate studies? What was your major?

I completed my undergraduate studies in China as a biology major with a focus on entomology. After undergrad, I received my Master’s in entomology at a graduate school in China, which was a three year program. In 1988, I immigrated to the United States to attend Cornell University for a five year PhD program. “I was an entomology major and a toxicology minor for my PhD. After that my research was more focused on neurotoxicology, so toxins that act on the nervous system. That includes many classes of insecticides (they are neurotoxins), and then also natural toxins like scorpion toxins and venoms.” 

 In total Dr. Dong completed 12 years of higher education.

Q: What drew you to your field of study? What are you passionate about?

I grew up on a research station in China for students studying silkworms and mulberry trees. My mom was a professor there, a biochemist. The silkworms were my pets; that’s how I got interested in insects. When I was in high school I started helping with the research- “dissecting the silkworm to find out all the different internal organs and figure out the glands that secret their silk. I found it fascinating. Many people don’t like insects, but for me I like insects.” My interest in toxicology specifically began from two different incidents. First, the village near the research campus grew rice, and the farmers sprayed Bt toxin on the crop. The pesticide managed to travel to the campus by wind and kill some of the silkworms that were being researched. When I observed this, I wanted to know why they died and the mechanisms behind it. “Another situation was when a farmer in the village got really sick by using some early class of insecticide- organophosphate. It was a spray; they did not use it right and a bunch of people got really sick. So I witnessed a lot of these and was wondering what was happening with the toxins? My fascination with toxins started a really long time ago, but I did not get a chance to do that kind of research in China. I did do physiology, entomology, and a bunch of different things, but the toxicology work I actually started at Cornell. I was always interested in why toxins are toxic, why are they so lethal. Why don’t some toxins just make you sick but kill you instantly?” 

Q: When did your interest in research start? 

My interest in research sparked during my PhD program in a toxicology lab. I was interested in learning not only the physiological effects of toxins but the molecular aspects of their functions as well. My first molecular lab experience was during my PhD program because there weren’t many opportunities for me during my master’s program. It was exciting to work with PCR (which was fairly new at the time), gel electrophoresis, and other molecular techniques.

Q: How did you start your lab at Michigan State?

My husband is a plant biologist, and he received his PhD a bit earlier than I did. When I graduated, he had a job at the University of Kentucky. I didn’t want to be separated from my husband, so I followed him there and began working as a postdoc. The lab I started working in was nice but didn’t really fit my interests. After a bit, I spoke to a mentor from Cornell who suggested I continue my research from Cornell at Kentucky. However, to start my own research I needed funding. I applied for the SF Grant, and my proposal was approved. While I could have continued my PhD work at Kentucky, I wasn’t happy at the university. There was racism in my department that prevented me from enjoying my work. Luckily, both my husband and I were offered jobs at Michigan State University. I used my SF grant there to continue my PhD research; we were both there for 25 years. 

Q: What was your project at Michigan State?

At Cornell, I started a project studying German cockroaches because they have been found to be resistant to all insecticides.” At the time nobody knew why these insects developed a resistance. You have to use a lot more chemicals to kill them.” I focused on pyrethroids (an ingredient in common insecticides) which target the sodium channels and kill the insects. “The hypothesis was maybe something changed in the sodium. Maybe there were more sodium channels or less sodium channels. There were all these different hypotheses.” In my research, I found that there are likely mutations in the sodium channels and that’s what makes them resistant. At the time I wrote the SF grant, my goal was to identify the mutations. When I settled at Michigan State and started identifying mutations, it turns out there wasn’t one or two mutations like originally believed but actually a lot more. “We were looking at the sequences using the mutation, but people said ‘How can you confirm that this mutation makes cockroaches resistant?’ So that is why in Michigan I set up a synapsis oocyte system. It was very challenging; even now only a few labs in the world can express insect sodium channels in oocytes. That was our advantage. We kept going with different mutations. We kept going with different sodium channels from different species because many past species develop resistance. We also want to understand selectivity. Why are they more toxic to insects, less toxic to humans? So we look into mammalian sodium channels.” Mammals have nine sodium channel genes, and we wanted to understand why human sodium channels are resistant to pyrethroids. In the lab, we discovered that the receptors on the mammalian sodium channels aren’t good for the pyrethroids to bind to and take effect. While studying sodium channels, we found a new ion channel called Drosophila Sodium Channel 1 (DSC1). The DSC1-family ion channels seem to be unique to insects but don’t affect mammals. It is a good target for insecticides that can be relatively safe for humans. 

Q: What was the transition from Michigan State to Duke like? Why did you come to Duke? 

I wanted a change personally and professionally. I wanted to live in a warmer climate for health reasons.  As for my career, my husband and I had a 25 year contract with Michigan State. Throughout those 25 years, we have both been offered jobs but never at the same place. Duke was an opportunity for both my husband and I to move and have positions together. There are also more opportunities to collaborate with colleagues. Once our contracts were up, we officially retired from Michigan and moved to Duke.

Q: What are your long-term goals for your research?

My long-time focus has been mosquitoes. Insecticides kill mosquitoes and in turn mosquitoes develop resistance. Mosquitoes use an olfactory system, which is how repellents work. I’ve been studying the mechanisms behind the functions on insecticides and repellents. Why exactly do repellents repel mosquitoes and insecticides kill them? In the next five to ten years, I hope to identify more receptors that mediate repellency and use it to develop more repellents. Another goal my lab has is to open mosquito brains to look at the circuits to see how they are activated and how this leads to certain behaviors observed. Currently we are only able to look into mosquito antennas, but we are working to develop a technique to study the brain in the future.  

Q: What has your experience as a professor been like? 

I love it. I’ve only taught one semester at Duke since I’ve been here. It was a seminar course about natural neurotoxins. The course discussed toxins produced by spiders, snakes, scorpions, etc. and the ion channel receptors for those toxins. Most of the students were engaged, and we had fun. This was also the first time I taught undergraduates because at Michigan State I only taught graduate courses. “Being a professor at a university, interacting with students is quite fun and a unique opportunity.”

Q: What advice do you have for someone who is considering a career in research?

“Find a research area that one is really interested in, work with experts in that field if possible and work diligently.”

While interviewing Dr. Dong, she exuded passion for science and love for her projects. She’s excited for the future of her research and the possible discoveries that can be made in the upcoming years. Dr. Dong is highly motivated and ambitious, and I’m grateful to have her as my PI; I have much to learn from her this summer.

Dr. Shyni Varghese: How did she get here?

Dr. Varghese was born and raised in India, traveling around the country frequently due to her father’s post in the military. She did primary and secondary school all over the country, although mainly in the southern state of Kerala. Afterward, she attended Mahatma Gandhi College, an institution that focussed minimally on research at the time of her attendance. However, she was able to conduct research more wholly at the National Chemical Laboratory of India, where she performed her Ph.D.

The National Chemical Laboratory, based in Pune, India, is a government research institute that investigates a wide array of chemical, physical, and biological sciences. Dr. Varghese studied both chemical engineering and polymer physics, investigating the thermodynamic properties of associating polymers. Her investigations gave her a thorough background on hydrogels, three-dimensional polymer chains that are often used in organ-on-chip models, the place where she eventually ended up applying her knowledge.

She next conducted her postdoc at Johns Hopkins at the Elisseeff Lab. The lab primarily studied tissue engineering, but Dr. Varghese worked with the PI, Dr. Elisseeff , to work on stem cell engineering and cartilage tissue engineering, a far cry from the work she did in polymer physics during her Ph.D. However, she says, “my thinking was influenced by it [Ph.D work], but directly, no I don’t use it.” She explains how her Ph.D work shaped her analyses and approach although it didn’t have direct applications to her current cell and tissue developmental work.

In 2008, Dr. Varghese got a Bio-Engineering faculty position at the University of California San Diego, where she spent 10 years continuing her work on bio-inspired materials and stem cell engineering. Her extensive work there framed how she conducts research and the research questions that she now develops at Duke University. Since she joined Duke Faculty in 2018, she has published numerous papers, served on various committees, worked as a MEDx Investigator, and worked as associate editor of Biomaterials Science, a Royal Society of Chemistry journal. She continues her work in various fields including developing smart biomaterials, extracellular matrix biology and engineered matrices, stem cell engineering, tissue regeneration, and organ-on-a-chip technologies.

Working under Dr. Shyni Varghese has been an incredible experience and I have gained invaluable insights about the way research is conducted and the degree of work that goes into maintaining the integrity of results and analysis. I’m looking forward to learning more from her and the rest of the lab during the remainder of the summer and on!

Dr. Koeberl’s Journey in Science

I really enjoyed getting to chat with Dr. Koeberl about his journey, mine, and science in general. It was nice to “break the ice”, get to know a bit more about him, and get some advice moving forward.

We started off by discussing his journey to where he is today. He began in his home state of Minnesota at Carleton college. He then went on to pursue an MD/PhD degree program at Mayo Clinic School of Medicine. He initially planned to pursue only an MD degree; however, opted for the dual degree after interviewers mentioned it. He completed his program in six years writing his thesis on hemophilia.

Dr. Koeberl then went on to UCSF to complete a residency in pediatrics. He followed this up with several fellowships in Medical Genetics at the University of Washington. After working as a pediatrician for a period of time, he began applying to faculty positions. He opted to take a position at Duke for several reasons. First of all, Duke was a place where many new types of treatments for metabolic conditions were being explore. Duke was also a great place to explore the use cases of then lesser known AAV vectors. These things which aligned with Dr. Koeberl’s research interests prompted him to start his career at Duke.

One thing that Dr. Koeberl likes about being a PI is the agency he has to study his own interests. The flexible nature of the work is also appealing. The biggest challenge that a PI faces is funding. It is something that requires continuous work and could necessitate some difficult decisions should money be tight.

His days can be varied but consist of about 4 broad things. The biggest of these is probably writing. This includes writing papers and grants, which also require lots of reading up on literature. Meetings with colleagues, funders, and others also take up a good bit of time. Some of Dr. Koeberl’s time is also spent in clinic where he sees patients with inherited metabolic conditions and as the medical director for the biochemical genetics lab.

Dr. Koeberl identified several things as being critical for one’s success in science. The first of these is having good people you can rely on. This was part of what helped him be successful in starting and continuing his research career. Dependable and capable people make science work. Another critical component of success in science is good communication. Being able to concisely and effectively communicate in oral and written modes is necessary to do well in science. The recommendations he had for developing those skills involved reading. This includes reading scientific literature about your field and books about scientific writing and grant writing (He acknowledges that they may be dry, but maintains that they are helpful).

On a lighter note, I also asked Dr. Koeberl what his favorite project was. It is a current project that we have going surrounding gene editing using CRISPR/Cas9 to treat a glycogen storage disorder. He is excited by the possibilities this technology has to offer and to see it go to clinical trial.

The fascinating background of Dr. Abraham

It is not every day you get to meet someone who lived through an important war in Nigerian history. Nevertheless, there I was, in the presence of my principal investigator, Dr. Soman Abraham. Born in Ethiopia but growing up in the eastern parts of Nigeria, Dr. Abraham lived through the Biafran war, also known as the Nigerian Civil War. He did his undergraduate and master’s program in Nigeria and his Ph.D. program in England. During his Ph.D. program, he became even more interested in research and decided to pursue a career in academia. Dr. Abraham speaks fondly of his mentor in England, who took it upon himself to write a letter to various individuals in the United States and requested a job for Dr. Abraham. Through that letter, he was able to come to the United States. He worked at Washington University in St. Louis as an assistant professor and took an interest in the immune system. During his research, he discovered the importance of mast cells in fighting bacteria.

As someone who has been to various corners of the world and met people in different cultures and communities, Dr. Abraham has a unique perspective on life. With a smile, he says, “People are all the same. They may be culturally different, but there are decent, good people everywhere.” Having the opportunity to work with people from around the world is one of the many reasons why he loves his profession. Being in academia grants him the opportunity to research abroad. He also admires that his career allows him to interact with students who stimulate his thinking and makes him reassess things. His students have diverse ideas that challenge him, and he finds joy in the constant renewal of his mind. 

He considers his trainees to be his most valuable career accomplishment, for they are now performing very well in various academic institutions, pharmaceuticals, federal agencies, and other industries. He finds deep satisfaction in touching the souls of those he trains. In retrospect, he suggests that without the letter written by his mentor in England, he probably wouldn’t be where he is today—when finishing up his Ph.D. program, he never planned to work in the United States or pursue a career in academia! As a result of the pathway that his mentor caved for him, he is continuing that legacy of serving his students without expecting a thank you in return.

The Scientific Journey of Dr. Pelin Volkan

The scientific journey of Dr. Volkan started in Turkey where she was born and completed her Undergraduate and Masters in Molecular Biology and Genetics. Interestingly, she initially had a strong interest in film but decided to go down the science route and into academia–an ambition she had since high school. This decision brought her to research neural development in the retina and what the genetic mechanisms were in that developmental process. She quickly learned that mammalian research was not for her, so, when Drosophila research gained traction in the 1990s, Dr. Volkan jumped at the opportunity. 

To further develop her career, Volkan knew she had to leave Turkey and ended up down the street at UNC-Chapel Hill to study fly genetics and development for her Ph.D. Her initial work in Bob Duronio’s Lab used Drosophila as a way to understand how cell cycles in the body are regulated through development. This gave her the background she needed in working with flies and learning fly genetics. At this point in her career, Volkan was still figuring out what she wanted to do for her postdoc. She found cell cycles to be fascinating, but it was too crowded and full of opposing ideas. This ultimately brought her back to Neuroscience and across the country to Los Angeles. 

“It [Neuroscience] has always been very interesting for me–from understanding how the brain is organized, how it orchestrates all our behaviors and thoughts, sensations, feelings, and I still wanted to stay in fruit flies, so I decided to do a postdoc in Howard-Hughes lab at UCLA.”

The next layer she wanted to unfold, using her background in developmental biology and genetics, was genetic programs that build nervous systems and connected cells and neurons in different ways to form neural circuits. Two questions that guided this research were 1. How do you wire these circuits correctly? 2. How is the architecture of the circuitry regulated during development? Little did she know that right when she started to get involved in this area, the fly olfactory system would get deciphered and the organization of the system would be already discovered. However, during the genetic screening, she stumbled onto a specific mutation and was influenced by a book she was reading about the life of Seymour Benzer (Time, Love, and Memory) to focus on how to quantify behaviors within the systems of neural circuits which ultimately led her back to North Carolina and to Duke. 

“What we found [at the start of the Volkan lab] was a sensor of environment that regulates the expression of these critical modulatory genes–what I have been waiting for all this time.” 

Why Do You Study That? Dancing Flies | Duke Today

Dr. Pelin Volkan

Today in the Volkan Lab, Dr. Volkan continues to study developmental neurobiology and is also researching how sensory cues depicted by the peripheral nervous systems regulate behaviors such as courtship and feeding to change the expression of certain genes. Outside the lab, you can find Dr. Volkan enjoying music, art, nature, martial arts, film, cooking, and most importantly, spending time with her family. She describes cooking as her zen moment and enjoys continuous motions such as chopping vegetables. Her love for academia and art is shown in her office with diagrams and images all over the wall of Drosophila, but the closest image to her desk is one of her family. 

From Turkey to UNC-Chapel Hill to UCLA and back to Duke University, Dr. Pelin Volkan has a robust scientific career full of many stories. Sitting down with her for even 30 minutes–this is apparent. Another thing that is apparent is her love for science and exploring something new; this desire has led her to where she is today and continues to motivate her as she continues her personal research and expands her work in the Volkan Lab. I am grateful and excited to learn more from Dr. Volkan this summer. 

 

YingYu the Stinky Tofu Advocate… and Scientist of course!

The endless opportunities in the USA have drawn numerous international students to its realm of scientific research, one of them being my mentor YingYu Lin.

YingYu was born in Taiwan; her older sister and she would love to walk around Taiwan and eat in multiple restaurants. YingYu’s favorite meal is Stinky Tofu (doesn’t sound appetizing but she lovesss it). When the time came for undergraduate school, she attended Taipei Medical University where college was very different than here in the US. She says that during her undergrad it was very chill and not super intense like how some of our classes can get. YingYu would hang out with her friends, watch movies (a proud Ravenclaw member in the magical world), and of course, eat Stinky Tofu. She discovered she truly wanted to be in the medical field when she entered her senior year of undergraduate and had to take a course where for six months she treated patients at the nearby hospital. She joined a cancer lab for about a year after where she went in knowing nothing but loved how everyone was open to teaching her everything. She loved the science, the chemistry, so to the US her next journey began: graduate school. At the University of Pittsburgh, she earned her master’s in Pharmaceutical Science but did not want to stop there; she yearned to learn more about the engineering of chemistry. Paving the path for a Ph.D., she entered Gerecht Lab at Johns Hopkins University where she currently is researching endothelial cells and pericytes. Her project revolves around the broken blood vessels caused by reactive oxygen species due to Diabetic Retinopathy. YingYu wants to provide a method to treat DR by reconstructing these vessels using stem cell differentiation to replace the dead endothelial cells with healthy ones. Seeing their relationship with pericytes, cells that lie right on top of endothelial cells, she works to discover how to build the functioning blood vessels to treat DR. After, hopefully, finding the solution and receiving her Ph.D. in Chemical and Biomolecular Engineering she aims to join the industry and use her skills to improve medicine either in the US for some time or back in Taiwan to be near her family (and Stinky Tofu). Additionally, visiting Finland and learning how to surf are top bucket list items that she would love to check off!

YingYu has been an amazing and inspiring mentor thus far and I have learned immensely from her not just about biomedical engineering but also about what my future could look like. I am delighted and happy to be working with her for at least 5 more weeks!

Interview with Dr. Scott Soderling

The Chair of Cell Biology at Duke University Medical Center, George Barth Geller Distinguished Professor for Research in Molecular Biology, Professor of Cell Biology and Neurobiology, and Director of the Transgenic Mouse Facility, Dr. Scott Soderling began his research journey while completing his undergraduate degree at Pacific Lutheran University. As a school with strong biology and business departments, and a close proximity to Mount Rainier conducive to pursuing mountain climbing, it wasn’t until a particular genetics class that Dr. Soderling knew which of the two majors to declare. Indeed, through an introduction to gene mapping using drosophila with a gene mutation, Dr. Soderling became fascinated with discovery – being the first to see something that has existed for millions of years. Ergo, he majored in biology with a concentration in biochemistry, going on to pursue a PhD in the department of Pharmacology at the University of Washington in a lab that studied cell communication, particularly signal transduction through the identification of enzymes impacting this process. Through this intersection of molecular biology and bioinformatics, Dr. Soderling concentrated on the role of cAMP and cGMP in the activation of kinase-mediated phosphorylation and thus cell signaling. During his postdoc at the Vollum Institute, where Dr. Soderling wanted to understand the impact of cell spatial organization and communication on physiology, he identified the WRP protein as being imperative for the WAVE signaling network, the latter of which directs actin reorganization in neurons (Soderling et al., 2002). Additionally, Dr. Soderling saw a clear link between what he was studying and human health when, in the case of a patient with an intellectual disability whose X chromosome and chromosome 3 had been translocated, there was a link between this phenomenon and a mutation in the gene for WRP. 

Today, Dr. Soderling and his lab focus on the neurobiology of neurodegenerative, developmental, and psychiatric disorders through proteomics, mouse models, and genetics. Although the job requires hard work to ensure success and presents challenges when grants or papers are rejected, Dr. Soderling believes the genuine enjoyment he derives from his career surpasses any such tribulations. In fact, this, combined with the freedom to be creative with his academic pursuits, being able to work with smart people from all over the world, opportunities for travel, and watching students and postdocs grow in the lab, is what makes him feel fortunate about the path he’s chosen. For Dr. Soderling, some of the best advice he’s ever received came from his father, who suggested that he choose between academia and industry according to whichever path offered the most options afterwards. Now, his own advice for students considering a career in science or research is to choose that which inspires the most passion and love, for if so, hard work won’t feel like work at all. 

Lastly, when asked if he wanted to share any embarrassing or funny moments he experienced in the lab, Dr. Soderling mentioned a practical joke his fellow lab members played on him while he was a postdoc. As he was reviewing data he had just gotten back for his paper on WAVE1 and the novel WRP protein, he received an email from an alleged professor at another research institute whose work mirrored his own. The implications of such an email were enough to make the blood drain from Dr. Soderling’s face. His lab mates let him sweat for a moment, before bursting out in laughter and confessing that it had been a ruse. Although the moment inspired a mixture of stress and embarrassment, Dr. Soderling laughs while telling the story.

A sincere thank you to Dr. Soderling for his time and the opportunity to learn about his own experiences with science and research.

My mentor: Rachel Keener

My mentor is Rachel Keener. She is a third-year Ph.D. student in the Ko lab in the MGM department. She went to the University of Georgia and majored in genetics. Her first interest in biology, particularly genetics, stemmed from her ninth-grade biology class, in which she learned about genetic diseases. She found it fascinating how one amino acid change/deletion can make someone so sick, yet people can have a whole extra chromosome and still be relatively healthy. Her interest in this field grew further when she took ap bio a few years later and learned about the impact of epigenetics and microorganisms on human health. By then, she had decided to pursue scientific research as a career. What she likes most about science is that she gets to be involved in the process of answering questions she’s curious about. Rachel especially likes studying the intersection between infectious disease and genetics. She has always loved genetics because it’s like problem-solving for her. She likes infectious diseases because it’s easy to see a direct impact by treating them. 

At the same time, Rachel also developed an interest in science policy and global health. She grew up in Atlanta, GA, where the CDC is headquartered. Her future goal is to work in an organization like the CDC, where she would mostly work on cases. She is enthusiastic about communicating science and contributing to policy-making, so she envisions her future career to be 60% research and 40% policy and communication. Her favorite part of the day-to-day as a scientist is the flexible nature of the work — she gets to manage her own time and project. 

Jun Zeng’s Pursuit of Science

My graduate mentor, Jun Zeng, is a 3rd year MGM student at the David Lab. Jun grew up in China, where he recounts loving “taking things apart” and learning how things worked. This love for discovery and exploration has carried him to where he is now, researching the microbiomes of cancer patients at Duke. This path was not always the specific plan- no one in his family had expressed a shared interest in research- but rather a product of continuously following his curiosity.

Much of that curiosity was sparked in high school, after reading the book A Short History of Everything by Bill Bryson. Bryson’s book about life and science ranging from chemistry to astronomy highlighted the wonder of science and was a strong factor in Jun pursing the field. In high school he studied slime molds: did you know that they communicate with chemical signaling? They can move?  Jun smiles talking about this work, reveling in how unique and complex the organisms were.

When he got to college at the University of Washington in Seattle, he knew he wanted to do research and overloaded his classes the first two years to get ahead on his majors Biology and Microbiology and clear up room for lab work during the rest of his time. Does he recommend this stressful, arguably fanatical decision? No. But did it let him spend the latter half of his college experience primarily in the lab, gaining an abundance of microbiology training? Yes. His lab studied bacterial competition and he was even part of finding a bacterial toxin secretion system that could be used for mitochondrial DNA editing. When asked why he reached out to this lab in particular, Jun’s child-like wonder reemerges: “It’s awesome, I mean it’s bacteria fighting each other. I thought it was cool.”

Jun started the MGM graduate program in 2019 and found his fit at the David lab. While he’s had his fair share of lab-related mishaps- such as lighting a bench with ethanol on fire- he finds joy in wet-lab experiences. He likes the process of doing experiments and prefers bench work to the more academic path of a professor. To that end, he wants to stay in the lab moving forward after graduate school whether that be in an academic lab setting as a researcher or in industry. Having received help from online groups of graduate students when he was applying for grad school, Jun also helps mentor international students from China who are applying for graduate programs in the US. He’s been an exceptionally knowledgeable, friendly, and helpful mentor for me these past few weeks and I’m excited to learn more about his experience with research!

My mentor: Yarui Diao, PhD

In undergrad, Diao studied at the University of Nanjing, China majoring in biotechnology. Cultural values drove him to pursue a career path as a scientist, rather than attending medical school (a contrasting priority to that of the US). Funnily enough, Diao stated his drive for biology in particular as a source of his struggles with physics and mathematics. His passion was then further fueled by a research program he entered in his junior year, working in the lab with PhD students. Later on when considering grad school as his next career step, he asked his PI about the process and considered programs close to home and thus he began his PhD in Biochemistry and Molecular Biology at Hong Kong University of Science and Technology. He focused his thesis on attempting to identify the proteins that impact the PAX7 gene. As background, proteins can function as an adapter protein to connect PAX7 with histone modification, which subsequently changes transcription and expression.  He discovered previously unstudied proteins and played a role in identifying the correct sequence mechanism. He was immediately blown away by his discovery and the implications behind it and became interested in gene regulation and epigenetics. When wrapping up his PhD, Diao applied to the Human Frontier Science Program (HFSP) fellowship, which centered around helping international students continue their studies in the US. As part of the program, scholars did have to enter a new lab and explore an alternative project to the research they had done thus far. He then began his post doc at the University of California, San Diego entering Dr. Bing Ren’s lab.  There he developed the first genetic screening method to study enhancer functions and was involved in a project to profile gene promoters and 3D genome organization. 

In his personal life, moving to a new country was a stressful transition. He arrived in San Diego with one luggage case and spent 2 months away from his family, particularly from his 4 year old daughter, who at the time, was still in Hong Kong. While the project was exciting, being in a new setting and in a new lab was incredibly difficult, especially given the language barrier. Communication with mentors and lab mates proved challenging, however the environment in the lab was quite welcoming; a factor which proved precedent when deciding on a faculty job here at Duke. Having faced some discrimination in the California as a person of color, he felt motivated to explore other states that would bring new experiences. Additionally, he felt the staff at Duke enjoyed their respective research projects and valued science on a similar wavelength. He continues to enjoy his research and his current lab centers on regeneration and genomics. 

While Diao has certainly progressed his career and now holds a high faculty position, he noted the many mistakes he made to get to where he is now. As a grad student that often included being lost in scientific conversations while still training and funnily enough, falling asleep during lab meetings and loudly snoring.



Dr. Emily Bernhardt on Ecology and Biogeochemistry

My mentor this summer is Dr. Emily Bernhardt, a genuine, kind, and established scientist who also happens to be the chair of the Duke University Biology Department. In these first three weeks of BSURF, I have gotten to know her a little bit more, especially through weekly meetings and setting weekly and semester-long goals (so-called “frogs”). I was able to talk one-on-one with her this past week regarding her passion for ecosystems ecology and biogeochemistry in relation to pollution and environmental stressors.

Many undergraduates come to college either not knowing what they want to do, or being absolutely dead-set on a pathway initially but then changing their plan completely throughout their education. Dr. Bernhardt, on the other hand, knew exactly what she wanted to do in her undergraduate education and kept with it: ecology. In her words, she has “never met anyone who actually wanted to do [ecology] at that stage.” She has always loved the outdoors and camping, while also maintaining interest in water quality and ecosystems. She also had a neighbor growing up who served in the Women’s Auxiliary Army Corps in WWII; this neighbor had collected different species throughout her travels and also other insects and plants, displaying many of them to Dr. Bernhardt. The only thing that changed slightly from her undergraduate experience at UNC  Chapel Hill to her graduate education at Cornell University was focusing on rivers rather than wetlands, but she still studies wetlands to this day.

Dr. Bernhardt said to me, “It could be that I’m remarkably uncreative because I just kind of decided this is something I wanted to do, and I just did it…I just knew.” I personally disagree with the statement that she is uncreative – she has found and still continues to find new ways to involve herself in academia and within university affairs. When I asked her why she decided to become a department chair, she described a year-long teaching for equity class she had taken that primarily taught anti-racism. She believes “it’s not enough to not just yourself cause harm – you have to actively do what you can to make things better.” She feels that by being a department chair, she has a lot more say in implementing these anti-discriminatory actions. She also strongly affirms: “It’s time. We gotta shift the demographics of the faculty so they look more like – well, America, but let’s start with looking more like our student body.”

All in all, I am really inspired by the work that Dr. Bernhardt does, in both her research and her involvement in representation and university functions. She is passionate and dedicated to her work, and her support of undergraduate research is also very obvious; not only does she support BSURF students like me, but also several Data Plus teams. Although I have only known her for three weeks, she has been nothing but open and willing to answer any questions I may have. It is very important to have people like Dr. Bernhardt in academia, science, and overall decision-making and influential positions, and I am grateful for the opportunity to work with her and in her lab.

The Importance of Zippers

In regards to zippers and Drosophila melanogaster, they both either fall into the category of things that annoy the everyday human being or the things that most people overlook in everyday life. Sure we know that zippers exist, but do we truly appreciate how helpful zippers are to most people? Do we take the time to admire how influential Drosophilidae species are to the advancement of science? I would assume that the answer to those questions is no. So, my project for this summer is to showcase the importance of zippers. In this case, zipper is the gene responsible for encoding the non-muscle myosin heavy chain allowing dorsal closures to occur in embryos. Dorsal closures are important because they allow embryogenesis to occur, so researching the alleles that allow dorsal closures to occur is beneficial.

My project is to investigate new zipper alleles and ‘pey’ alleles. The ‘pey’ alleles have mutations, but the location of said mutations are unknown and my job is to locate the mutations. My project also falls under the larger question, what is the function of myosin and how the heavy light chains and regulatory chains assist with forming myosin filaments. Although some of these alleles have been studied, with every new cross of drosophila genotypes there is new information to learn about drosophila genotypes and embryos.

This project is extremely fascinating as well because of how intricate my everyday tasks are. From imaging drosophila embryos to carefully collecting drosophila embryos to sorting the flies by sex, there is always the need to be meticulous. With that being said, I am excited to continue with this project and hopefully discover new information about zipper and ‘pey’ alleles.

 

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Watching the Mice DANNCE

Over the past few years, the lab has been working on developing an imaging box, which takes multi-angle videos of mice in a box, observing their locomotion and other behavior. It provides a way for us to more accurately quantify the behavioral phenotype we often observe in mice due to our experiments. Just recently, the box was finished and put into use, and now it’s time to test and verify its efficacy.

When we look at mice behavior in the lab, we typically use an algorithm like 3-Dimensional Aligned Neural Network for Computational Ethology (DANNCE), which is more robust than traditional techniques because by using machine learning, it can create a virtual diagram of a mouse using points in space and analyze how those points move about over time.

DANCCE Algorithm at Work from Dunn, T.W., Marshall, J.D., Severson, K.S. et al. Geometric deep learning enables 3D kinematic profiling across species and environments. Nat Methods 18, 564–573 (2021). https://doi.org/10.1038/s41592-021-01106-6

This gives us a more refined way to quantify mouse behaviors like grooming and turning associated with Parkinson’s disease, the lab’s ultimate focus.

Our experiment consists of testing two variables, drug dosage and the circadian rhythm, on mice behavior, locomotion specifically. By using a technique called Principal Component Analysis, we will take the data of mice moving in 3-dimensions and compress it onto a single image from which we can see differences in mice locomotion. With further analysis, we hope to be able to show that our box does indeed pick up on the differences, no matter how subtle, between mice behaviors in a quantitative and informative way.

AAV Gene Therapy for Mitochondrial TFP Deficiency

My project this summer is studying the effects of gene therapy for a mitochondrial trifunctional protein (TFP) deficiency. This autosomal recessive mutation effects the function of an octamer protein complex that is responsible for fatty acid oxidation as seen in the figure. Even though our mutation only effects one subunit, it alters the folding of the complex rending the entire complex inactive. This process not only breaks down fatty acids, but it also supplies the acetyl-CoA needed for the citric acid cycle which is produced by the step labeled 3 by the beta subunit. It effects the liver and heart heavily since both rely heavily on fatty acid oxidation as a source of energy. Since this process is unable to occur, those organs are not able to function optimally and have fat build up in their cells (the medical word for this is steatosis). Muscles, which sometimes depend on fatty acid oxidation, are also affected. This condition shortens one’s lifespan significantly, with cardiomyopathy being the typical cause of death.

Our lab’s goal is to correct this using gene therapy to replace the missing enzyme. We are currently trying to do this using an Adeno-associated viral vector (AAV). For anyone not familiar, this can be thought of as a trojan horse. We enclose the DNA coding for the protein missing within the virus and use the virus “machinery” to get inside the cell. The goal here is that the cells can now make the protein, hopefully curing or improving the condition. Some problems that can arise include the cells not taking up the virus, immune response, and the DNA being lost as the cells replicate.

We are testing this AAV therapy in a mouse model with a TFP deficiency. We administer the treatment in affected and control mice. We plan to perform a variety of tests to see if it is effective. This includes glucose tests, strength tests, tests to look at the amount of fat in the liver, Western blots to measure protein levels, and looking at the stained tissue under the microscope to name a few. My role this summer is to help with these tests and look at the data they produce. So far, I have done background reading on the condition, genotyped new litters using PCR and gel electrophoresis, ran some of these tests on our mice to assess the effectiveness of our therapy, and analyzed some of our results using graph software. In the next weeks I will learn how to run more of the tests we need to evaluate the treatment and perform some of them. I’m very excited to follow this project and see where it goes throughout this summer and beyond.

Project MutaLib

Four different bases can be stringed together in a mind-boggling amount of variations. They form one of twenty amino acids that themselves can be combined to form various proteins. My project indirectly supports my lab, Neurotoolbox, in its endeavor to improve fluorescent proteins that are utilized for spatial and temporal resolution of neurons in the brain. There are two notable types of proteins that the lab uses. One protein can be used to activate a neuron by shining a light with a specific wavelength. The other protein can fluoresce upon activation by its respective neuron. Both of these proteins have numerous capabilities in the field of neuroscience and in identifying nerve tracts.

My project within this lab is to facilitate the pursuit of improving the biological capabilities and optimizing the performance of these proteins. My principal investigator, Yiyang Gong, provided me with a MATLAB dataset housing all the reads of a mutation-induced sequence of one of the aforementioned fluorescent proteins. There are over 350,000 different mutated sequences each with their respective coverage (number of reads/voters) and quality scores. The original sequence is known, but the issue is the successful discernment of true and fake mutations. Over 55% of the dataset has incredibly low coverage (1 or 2 reads), 15% has moderate coverage (3 reads), and the other 30% has high coverage (4 to 20 reads).

When there are few voters and an inconclusive quality score, what is the true mutation? What about if both reads have a perfect quality score yet they disagree? These are the questions I have to answer, notably when the coverage is only moderate to low (3 or less) which makes up 70% of the dataset. Through Python data analysis, probabilistic modeling, and machine learning applications, I need to clean the dataset and create a library that associates a barcode (tagged to the end of different mutated sequences) with its respective SNPs. The mutations would later be processed to determine which sets of mutations would improve the performance of the fluorescent protein (my next project after completion of this one).

Trem2 effect on Macrophage Polarization

The Diao Lab primarily focuses on regeneration and genomics. My specific project revolves around the polarization of macrophages and induction on behalf of the TREM2 gene. 

Background: As a response to muscle injury, the immediate cellular response is the production of immune cells, particularly macrophages as early infiltrates. M1 type macrophages react initially, serving as sources of inflammation through the presence of pro-inflammatory cytokines, such as TNFα, IL-1, IL-6, IL-12, etc. Throughout healing, M1 type macrophages are replaced with M2 phenotype macrophages typically around the Day 3 mark. The M2 phenotype macrophages possess a more regenerative aspect and reduce levels of inflammation through production of anti-inflammatory cytokines such as IL-4 and IL-10. Additionally, they stimulate the breakdown of debris (damaged tissue) to promote healing. However, the change in phenotype of the macrophages appears to be mediated by the TREM 2 gene which induces the M2 macrophage. “If this transition is delayed and the M1 phenotype is prolonged, inflammatory cytokines persist and myogenesis is impaired, demonstrating the importance of this precisely timed phenotypic switch. Once M2 macrophages are present, they mark the beginning of the regenerative phase” (1).

The purpose of our project is to analyze the effect of the TREM 2 gene on macrophage polarization. By knocking out the TREM2 gene and measuring levels of respective macrophages, correlations can be stipulated as to whether or not the TREM2 increases levels of efferocytosis and phagocytosis or plays a role in inflammation. Based on the articles I have read thus far, there is an indication that the TREM 2 gene drives macrophage polarization which allows the M2 macrophage to begin its process of healing. In the lab, we have knocked out the TREM2 gene in mice and are analyzing the cells collected from animal muscle tissue. Once the macrophages are separated, they are run through FACs sorting, which allows us to categorize specific cell populations based on phenotypes and to better understand the characteristics of a single cell population. We then isolate the RNA in order to better gauge which genes are being expressed and their relative abundance through qrt-PCR. We look for specific M1 and M2 markers in order to better understand the turnover of the macrophages and whether or not one is being expressed more or less as a consequence of the TREM2 knockout. We have already thus far seen induced ischemia on the mice in which TREM2 is knocked out, which is an indication of the progression of peripheral arterial disease (revealing the regenerative aspects of TREM2). Further analysis needs to be completed, yet on a larger scale, exploring the process of macrophage polarization not only better aids our understanding of the mechanism, but can provide insights into new strategies for approaching and amplifying treatment targeting various diseases. 

  1. TA;, Wosczyna MN;Rando. “A Muscle Stem Cell Support Group: Coordinated Cellular Responses in Muscle Regeneration.” Developmental Cell, U.S. National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/30016618/.