Author Archives: Julia Marshall

What a whirlwind

I can’t believe BSURF is over. I feel like I became so used to the 9 to 5 workdays it’s hard to believe they’re over for who knows how long. It’s surreal. I’m so thankful to have been given this opportunity to dedicate two full months to immersing myself in research. There was definitely a learning curve in the beginning as I had never been in a biology wet lab before. But by the end, I felt like I started to get a grasp on what I was doing and was working almost independently. We struggled in the beginning to get results and were forced to go back and optimize our procedure. After we did this, things really took off and we began making small findings, which was really exciting. I’m so happy that I got placed in the lab I’m in now. My mentor was such a good teacher and worked so hard to make sure I understood not only what I was doing but why it was important. My PI also worked hard to take an active role in my experience, teaching me the background information and checking in on my progress and how I was feeling about the whole process. I felt so supported in my lab and worked so hard to make them proud. There were many times when I was too hard on myself and my perfectionism hurt me. But wherever I struggled, my mentor and PI were there and ready to develop a plan to solve the problem.

A lot for me has changed this summer. I went into this program having ideas about my career choice that are slightly different from what I think I want to do now. This experience was incredible and allowed us to develop a realistic perspective on what doing research is like. It has confirmed for me that I love research. I love its hands-on nature, freedom, and flexibility. But I also realized how important other fields are to me too and how what I really wanted to pursue was an integration of biology with other fields of interest to me such as ethics and law. It wasn’t an easy realization to come too and in a way made things that much more unclear. It was scary but exciting. My heart will always be with biology and I still fully plan on continuing to take part in and engage with research. But I realized I needed to include some of my other interests and that I need to work to integrate them in some capacity in my career.

As for how this summer changed my view of science, I don’t think it has changed my view much. But I will say that knowing something and experiencing it are two very different things. To name a few: I knew research was challenging and filled with many obstacles. I also knew that producing interesting results is exciting in a way not much else it. I knew these things going into the summer, but I had never really experienced them myself in a real-world setting. This experience has allowed me to experience those things for myself rather than relying on what someone else tells me. I’m really proud of myself for my perseverance when I ran into obstacles and the final product I’m leaving this program with. It was truly an eye-opening experience and I’m so grateful to have had it and for everyone who dedicated so much time and energy to my development as a prospective member of the field of biology.

A Reflection on Dr. Lawrence David’s Talk

Over the last two months, we’ve had many different speakers come to give us talks. It was surreal for me to be in the same room as many people who have conducted breakthrough research (even one Nobel Prize winner!) and accomplished so many things in their lives. It was exciting for me to learn about their work and how their projects and questions evolved. But so many of the pressing questions I had for our speakers regarded what paths they took to get to where they are now and how they found their way. It was really encouraging for me to hear about what their experiences were like at my age and allowed me to be less intimidated by them and relate to them more.

One of the talks that will stick with me is Dr. Lawrence David’s. Dr. David is a fairly new professor at Duke and was hired 5 years ago. His lab studies the microbiome in the human gut and how what you eat affects it. He was the only researcher whose work involved humans as tests subjects, which I thought was really cool. But his talk didn’t focus primarily on his research, rather it focused on how he got to where he is today. He talked about his time at Columbia as an engineering student, at MIT as a Ph.D. student, and at Harvard as a junior fellow. His discussion was peppered with funny anecdotes about things like the time he spent two months eating street food in Thailand as part of his Ph.D., seeing how it affected his gut’s microbiome. He also had a very earnest discussion with us about the frustrations of research, questioning the graduate school route you choose, trying to fit into the world of science, the times you feel like you don’t belong and don’t know what you’re doing.

Some of his lessons were:

  1. Research is going to get weird – that means a breakthrough is coming
  2. Not everyone in the room is smarter than you. A third are but aren’t interested in showing it off and want to be your friend. A third are about as smart as you and can be considered friends as well. Another third isn’t as smart as you but want you to think they’re so much smarter than you are.
  3. The moment you think you know what you’re doing is the moment you’re given your next challenge (graduation).

I think self-doubt is something everyone struggles with when they’re trying to find their way and it was really nice to hear him address than and talk about how even now there are times when he wonders if he should have gone to medical school. I felt like I could relate to some of Dr. David’s experiences and that was really exciting to me. His story emphasized the importance of an open mind, trusting yourself, and welcoming change. His talk is definitely something that I won’t forget and his words of wisdom will continue to resonate with me as I continue on my journey into science. I feel so grateful to have had this experience and hear from so many brilliant, fascinating people. I’ve taken so much away from their talks and they’ve given me a lot of perspective.

Abstract and Progress

I’m happy to say in the past few weeks I’ve made some progress with my project. While the beginning was a pit rocky, after a few rounds of optimization and discovering we were using a faulty antibody results have started to come in and I couldn’t be more excited. What I’ve been told is that’s kind of how science goes and that a lot of results come in very quickly towards the end of a given amount of time. I’m excited to see what comes out of these last two weeks!


Ubiquitination is a cellular response to damaged proteins caused by oxidative stress. But the mechanisms and targets of different ubiquitin structures have not been well characterized. This research investigated the ubiquitinating enzymes and relative targets related to K48 ubiquitination, a signal for protein degradation, and how the efficiency of relevant molecular machineries, the proteasome and deubiquitinating enzymes, is impacted by different levels of oxidative stress. This was done by using mutant yeast strains with ubiquitinating enzyme knockouts, exposing them to oxidative stress, and analyzing their K48 ubiquitin content with a western blot. Ribosomal isolation and K48 ubiquitin antibody tagging was used to examine ubiquitin targets. Proteasome and deubiquitinating enzyme activity was analyzed using a substrate that fluoresces when processed and tracking light levels emitted by stressed cell lysates. Our data suggests the K48 ubiquitination system involves multiple ubiquitinating enzymes and genes and the greater impact of oxidative stress on the deubiquitinating enzymes than previously anticipated. Improving our understanding of K48 ubiquitination in stressed cells could allow us to better understand diseases such as Parkinson’s and Alzheimer’s that are caused by protein aggregates in stressed cells, and potentially provide new targets for treatment to make cells more resistant to stress.


A Day in the Lab

Every day I spend in the lab is different. So it’s hard to choose a prototype of my day. The protocol for my lab work usually runs on a weekly basis and each day is an incremental step of completing a western blot in combination with optimizing previous western blot procedures and troubleshooting problems with antibodies and film resolution. I start my morning by doing prep-work, usually getting ice, labeling tubes, or turning on centrifuges, and thinking through what I have to get done for that day. On our lighter days of the western protocol, we conduct additional experiments that analyze K48 ubiquitination from different approaches. On these days, a lot of coordination is required to keep the timing correct on both experiments.

When people have a break in their work, around 12 PM, everyone in the lab goes for lunch together. Having lunch together is very important in my lab. They want to facilitate a culture that encourages us to just hang out outside of the lab in a more casual setting. It’s one of my favorite parts of the day. Besides the fact that by noon I’m starving and in need of my third coffee, I like to get a chance to talk to the members of my lab about their weekend and random topics without the immediate distraction of experiments in the background. The dynamics of the lab are great. Since it’s a relatively new lab, there are only 5 people in it: my PI, the lab manager, a postdoc, another summer undergraduate research assistant, and me. This has allowed us to get to know each other better due to such close contact. Some days we’ll take a break and go out for coffee and watch the world cup game that’s on. In the Silva lab, it’s not just about developing the ability to work with one another, but also developing relationships between lab members.

After lunch, we pick up where we left off on our experiments. I’m usually kept really busy while in the lab, running around mixing solutions and processing samples. More often than not, Latin music is being played in the lab while we work and sometimes big world cup games are streamed over the speaker. It’s a really good environment to work in and I’m really happy to be there.

Social Hierarchy’s Affects on Male Baboon Stress Levels

The entirety of this past week’s BSURF meetings were dedicated to giving Chalk Talks, giving everyone in BSURF an opportunity to learn about and engage with each other’s research. My eyes were opened to the range of topics being investigated. Previously I had some concept of what my fellow BSURFers were studying using blanket labels like “neurobiology” or “plant biology” and what I had learned from their blog posts. But with time having passed and projects having progressed and evolved, Chalk Talks gave a new opportunity to understand the various research projects in a deeper way and have lingering questions answered. As someone who is very much a visual learner, the emphasize on drawings and schematics in these presentations really helped to develop my understanding.

A project I found really interesting was Christine’s. Her project was a little different from the other research being conducted in BSURF. Her research focuses on studying baboons and hierarchal stress amongst males. Her main question was, “Do alpha and low-ranking baboons experience different sources of stress?” I found the infrastructure involved in this research and the previous findings to be really interesting. Previous research has found that the alpha males experience high levels of stress due to energetic costs, while the beta males experience significantly lower levels of stress. Interestingly, as you move down the social hierarchy, relative levels of stress increase due to increased psychosocial stresses. I found this distinction between stress sources as they relate to social hierarchy surprising and fascinating.

Additionally, I was intrigued by the large scale, international logistics involved in this research operation. The population of baboons being studied is Kenya and monitored by a team of people that analyze social interactions to determine social hierarchy and collect fecal samples for analysis. These samples are sent to Duke and the relative stress levels of the baboons is determined by analyzing cortisol levels. The amount of coordination and cooperation between those in Durham and Kenya is truly remarkable.

I think Christine did a great job in her presentation. I learned a lot about an area of research I know very little about and I’m excited to learn about her findings  and their possible implications.

Interview with Dr. Gustavo Silva

Where did you go to school and what did you study?

I went to school at the University of Sao Paulo in Brazil. I majored in biology. Over there the course is very broad. So, we learned everything from zoology to botany to ecology. But I always liked molecular biology. I was doing research looking at the regulation of the proteasome, or how proteins are degraded. I did my Ph.D. at the same institution. This is the best university in Brazil so there was no reason to go anywhere else. It was kind of a follow up of my undergraduate research. When I finished that, I thought I could use a lot of large scale proteomics methods to look at a lot of different questions that were fascinating to me at that time. I did a postdoc at NYU and studied how ubiquitin, a particular protein that is a marker for degradation, can have multiple functions. We were finding this very interesting function now in protein translation. This is the research that I took with me and now in my lab this is one of the goals–to try to understand the multiple functions ubiquitin can have in cell biology and diseases.


Did you always know you wanted to go into science?

No, I don’t think I understood what science was until I made it to college. I think I was always very curious. I was always trying to understand things. Biology wasn’t even my best subject in high school. But I think most of the questions that I had were about how things work and people were always telling me, “You have to go to college to learn that.” My first semester in college I was taking a genetics course and it was a very hands-on course with drosophila and doing a lot of crossing and analyzing data. I thought it was fascinating. It also included a lot of the history of genetics, going back to Mendel, and you started to see how all the knowledge was built. This was fascinating to me. I thought, “Wow this could be a profession. Maybe I want to do that.” So, I started looking for a lab to do some research. Proteins were something I always liked and at that time I was also interested in exploring immunology. But I joined a lab that was looking at protein degradation and I fell in love.


What have been some of your goals for you career and have the changed between the time you were in college and now?

When I was in college I never thought I’d be in a position like the one I am in now. There were a lot of challenges and barriers. I think I always aspired to have my own lab. I thought that it would be really interesting to do your own research and go after your questions. But now I see that in this particular position as a professor especially at an institution like Duke, you can do a lot more than just the bench work. I think it’s important to be a good mentor and to shape the new generation. I think it’s important to open up opportunities for people. Science is a big component of my career and the things that I like to do. But I think I can do much more. I’m still learning. This is still my first year. But I think the goal is always to learn more.


What is it you like about doing science?

I think the coolest thing about science is that it gives me the intellectual freedom to pursue questions that I want to pursue. So, every day that I come into that or that I’m reading research I have my questions that I can challenge and motivate myself to go after. There’s never a routine there’s just stimulation that keeps you on the edge and you’re always learning. I think that’s the coolest thing about science.


What would you change about doing science?

How we communicate science to people outside of the academy a lot of times science becomes a very regional thing that doesn’t get to the people who could actually benefit from it. Some other steps about the profession itself – it’s super demanding in some respects which push people away from science. Also, how science is taught in a lot of different ways. I feel like there is a tendency to push people away from science and away from knowledge. It’s not only because people aren’t interested but also because we are not doing the greatest job in teaching people to see the beauty we see in science and the excitement we feel about a discovery. Those are a couple things that we can hopefully change in the near future.


What are some of your disasters in the lab or most embarrassing moments?

When I was an undergraduate—probably my first month, somebody had a system to cast a gel and somebody couldn’t take it out so it got stuck. They said, “Hey can you try to get it out?” I was young and I was thinking I was strong and could do it. But when I tried to get it out, I broke it in half. I was like, “Uh oh.” I had just broken a system in two and they had to buy a new one. That was like the first big thing. But we still do a lot of small mistakes. I don’t think I’ve ever set anything on fire though.


What lessons do you have for my journey into science?

I think journey is the exact would you have to use because it’s not only about what you do but about what you learn. The science is important but there are a lot of skills you can develop over time that will be applicable to whatever you want to do. If you want to get a Ph.D., go to graduate school, or medical school, I think all those skills can be transferable. As a scientist, we develop so many things that we underestimate that they can be very useful. Keep thinking about teaching, mentoring, and the importance of all of those aspects. Keep your eye on the prize and I think all of that will help you a lot in your future

Week 2: What am I doing?

The Silva lab researches how cells respond to stressful environments. When cells are put in a stressful environment, many of their proteins are damaged. Damaged proteins can result in many adverse consequences for the cell, so in times of stress the cell works to remove these proteins. Eukaryotes have evolved special machinery to recognize and tag damaged proteins using ubiquitin. Ubiquitin is a short protein used to post-translationally modify other proteins and can signal many different things such as degradation of the tagged protein.  Ubiquitin accumulate in the cell, possibly resulting in negative outcomes. This accumulation and disruption of the proteasome degradation system is thought to be related to neurodegenerative diseases like Parkinson’s and Alzheimer’s disease. However, very little is understood about how the ubiquitin proteasome system is related to disease and many ubiquitin pathways and targets remain to be characterized. Additionally, stress intensity can also impact the efficiency of the proteasome.  At low levels of stress, efficiency can increase whereas at highs levels, the proteasome’s functionality is reduced. However, the causes for this response are not well understood. The Silva lab’s research focuses on characterizing ubiquitination pathways and their corresponding cellular responses as a result of oxidative stress.

My project relates to one specific kind of ubiquitin modification, Lysine 48 (K48) ubiquitination. This tag serves as a signal for protein degradation. My project focuses on characterizing K48 ubiquitination levels in cells experiencing oxidative stress. Some of the big questions of my research project are what enzymes are involved, specifically the E2 and corresponding E3 enzymes that ubiquitinate proteins. As well as what are the targets for K48, how K48 ubiquitination of ribosomes vary in stressful environments, and how these modifications impact translation. My current project is taking many different approaches to characterizing the usage of K48 ubiquitin in response to stress. I’ve started out this research experience looking at general levels of K48 ubiquitination in wild type yeast cells under different levels of oxidative stress. After this initial experiment, I’m studying K48 levels in mutant yeast stains that lack E2 enzyme genes in order to test which enzymes are important to the K48 ubiquitination process. After this, I will explore how the proteasome activity and deubiquitinating enzymes in the cell are affected by oxidative stress and then how the frequency of K48 modified ribosomes changes in a stressful environment. Characterizing this pathway could provide greater insight into the biological underpinnings of serious neurodegenerative diseases and help this area of research be one step closer to finding a cure.

1 Week Down!

I’m not sure that I came to Duke this summer with many expectations about my research experience in mind. Rather, I had many different hopes regarding the dynamics of the lab and what kind of project I would conduct and what work it would entail. I was extremely nervous prior to the start of the program. I was eager to make a good impression on the Silva lab and work towards holding my own within lab and work independently and collaboratively. The Silva lab studies ubiquitination and protein degradation in cells in response to oxidative stress, which is thought to be a foundational biological factor in the development of diseases like Parkinson’s and Alzheimer’s. My two biggest hopes for this research experience were that I would be genuinely fascinated by the research I was doing and that I would build a relationship with my mentor.

After my first week, I’ve gained a much clearer idea of what my research experience is going to be like this summer. I’m extremely excited for what’s to come. I expect my days to be busy and intellectually stimulating. I expect to be challenged to push myself towards working independently. I hope that through this experience I will develop a clearer idea of the career path I want to take, whether that be as a researcher, or working in an intersection of biology and another field such as law. I think it’s such a valuable experience to be able to get a taste of what a work week would feel like as a researcher in the biological sciences. Some of my goals for this experience were to dive deep into a section of biology, develop my laboratory skills, learn new techniques, get to know the people in my lab, develop mentorship relationships, grow my confidence in a lab, and think seriously about what aspects of research really draw me in.

This first week went really well and I think I took some solid steps towards my goals. In the big picture of carrying out my research project, this week served kind of as a trial run for the procedure. I learned about culturing yeast, exposing yeast to stress inducing conditions, estimating protein concentrations, and conducting western blots. Next week, we’re going to repeat this procedure using mutant yeast strains to study ubiquitination under oxidative stress. I’m excited to work with mutant yeast strains and start data collection for my experiment. I am eagerly, yet nervously awaiting the time when I’ll work solo on my project.


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