Eric Sha | November 11, 2022
DNA replication is a critical process that ensures the growth and continuity of cells. Thus, it is crucial to ensure that no mistakes are made during replication. Dr. Jared Nordman’s lab focuses on this regulation of replication and on the replication machinery used by cells. In addition to being the principal investigator of the Nordman lab, Dr. Nordman teaches Biochemistry I and II (BSCI 2520 and BSCI 4265) here at Vanderbilt. I sat down with Dr. Nordman to talk about his research, career journey, and experience teaching biochemistry during the COVID-19 pandemic.
Research in the Nordman Lab
Thank you for taking the time to talk with me today. Your lab focuses on DNA replication during development. Can you tell us more about that?
Replicating your genome is really important for every organism. As we think about how DNA replication is regulated, we have to think about the context of development. A lot can change during development, such as the way that chromatin is structured and the way the cell cycle is remodeled. These are known effectors of how you replicate your genome. We use flies for experiments because flies can typically replicate the genome in about 8 hours, but in some developmental contexts they can replicate that same genome in 3 minutes. We can exploit those dramatic changes to identify how the replication machinery is changing during development, with the ultimate idea of understanding how you accurately replicate your genome every time the cell divides.
What findings has your lab made?
We’ve identified new factors that are important for replication and replication factors that have roles we didn’t really expect. We’ve recently been interested in a protein called Rif1 that controls the timing of replication, specifically in S phase when a given DNA sequence is replicated. We found that this protein interacts with the replication forks (which are known to replicate the genome) and showed that Rif1 has a function at replication forks that nobody had found before. Another recent paper showed that a subcomplex in the nuclear pore affects replication initiation through mechanisms we don’t totally understand yet. We’re really excited to pursue that.
What are some cool new methods/techniques that your lab is using?
We love trying out new methods! One thing we’re really excited about is using quantitative mass spectrometry to identify different protein complexes. We collaborate with Dr. Lars Plate’s lab, which has been really helpful. We do a lot of genomic type assays here, where we use Illumina-based sequencing methods to identify where a given protein binds through the genome. We’ve also developed techniques to look at where R-loops are formed. These are sites of RNA/DNA hybrid formation that happen as a binding product of transcription and are important for genome stability. A student in my lab adapted a technique called DRIP-seq and mapped those changes during development.
How do you see the field of biological/biochemical research changing in the future?
When you look at the top journals, you see lots of new quantitative techniques being applied. I think that’s always been a theme throughout the history of biology, at least since the onset of modern molecular biology. Some of these creative methods include single-cell sequencing technologies and high resolution mass spectrometry. We’re at this marriage between technology and biology that we’ve never had before, and this is driving biology forward. We take it for granted how rapidly we’re able to make a COVID vaccine, and I think that just shows how much biology has progressed.
How did you get into research? What about DNA replication specifically?
I guess I got into research by accident! I had a TA in undergrad that suggested I reach out to someone about doing research. At the time, I had no idea that people did research as a career. I ended up joining that lab and was fortunately very successful as an undergrad, which kind of jump started my career path. I could ask whatever questions I got excited about and pursue those at levels of detail that are near insanity and love what I do every day. Once I realized that was an option, I knew that was what I wanted to do. The lab that I first went to was a DNA replication/repair lab, and I never really strayed after that. I’ve always been fascinated with regulation; replication is such a complex process that requires so much regulation and input from different signals and coordination of different protein complexes. You can replicate billions of base pairs of DNA in just a few hours without making a mistake, and that really blows my mind.
Who are your biggest inspirations in research?
My biggest inspirations are definitely my mentors that I had over the years. My undergrad mentor was really fantastic and believed in me and planted the seed to get me going. Most importantly, I’d have to mention my graduate advisor, Dr. Andrew Wright, who just made the best environment to work in and kept me excited. He made me realize that great scientists can also be great people. The same is true for my postdoc mentor, Dr. Terry Orr-Weaver, who was super inspirational. The amount that she was able to accomplish in her career as a woman in science in a time when things weren’t so favorable for women in science is remarkable. She’s the ultimate professional and I wanted to be just like that when I grew up.
What advice do you have to young scientists?
Find something you love doing. There will be lots of setbacks and challenges, and you need the motivation to keep going. If you don’t love what you’re doing, you’re never going to be successful. After you’ve done the 1000th assay that didn’t work, what’s going to motivate you to do the 1001th assay that is going to work? So much of what we do is failure, and you have to acknowledge it, accept it, and keep moving forward.
Teaching Biochemistry during COVID
During the COVID pandemic, you adopted the flipped classroom approach in your classes. How has COVID changed the way you teach? Was there anything you didn’t realize about teaching before COVID?
Active learning strategies are well-documented to be better tools for learning. The problem is, it’s a lot of work on our end to actually flip the classroom. It’s relatively easy for most professors to walk in and give a lecture for a class that they’ve taught a lot. The thought of flipping the classroom was really daunting, but COVID forced us to do that. I think a lot of us wanted to do it, but were intimidated by the amount of work it would be to flip the classroom. To be honest, I was also nervous about flipping the classroom in such a large class. I recently started teaching a smaller class, and it wasn’t as intimidating to flip the classroom there, as you had somewhere between 8 and 25 students. To do that with 150 students feels like another challenge. I had an idea initially of what I wanted to do in the classroom setting, but when we first flipped the classroom, I was wrong and had to come up with a better system on the fly. I don’t think my expectations were quite right at first, so that had to be adjusted. I also didn’t anticipate the learning gains we’d see. I recently gave an exam that I thought was pretty difficult and the average was a lot higher than I expected. I think a lot of it was because we are able to do so much work in the classroom and go deeper because of the lectures watched outside of class. I’m seeing that really pay off this time around. I also have much better interactions with the students throughout the semester because I get so much one-on-one time with everybody by answering questions on the problem sets. I don’t think I realized how beneficial [getting so much one-on-one time] would be for me and the students.
What’s your favorite part of teaching biochemistry?
Getting to know the students for sure. It’s nice to make connections with students, even in a large class like biochemistry. The fact that I still get to know those students and make a personal connection is really important. I have no doubt that the biggest contribution I will have on science is motivating and inspiring students in the next generation. Some of these students will carve out a path in research and do something really important. That’s going to make a much longer-lasting impact on science than my research will.