Author Archives: Jaan Nandwani

I started this summer diving in at the deep end with my first lab meeting, where I was taken aback by how much I didn’t know, but excited to begin. Fast forward to my last lab meeting of this summer, and I can’t believe how much I have learned in 8 weeks. At this meeting, I was presenting my work from this summer and I finally began to keep up with (some) of the conversation.

My summer research experience has definitely surpassed my expectations as I have learned more than I could have ever imagined. I have finally got a sense of the literature in my field and worked with my lab mates to learn more about the focus of the lab. I have also learned many new technical skills including western blot analysis and genotyping.

I realized that I want to continue scientific research and thrilled that I will be continuing this project with this lab in the fall. I am very grateful for my lab mates and mentors who helped me develop a passion for what I am studying. Their support and encouragement really pushed me to to be more dedicated to this experience.

In addition, I am so thankful for the bonds and connections I formed with the BSURF community. We had a lot of fun times exploring Durham or even just hanging out at Swift. As a whole, I feel that this summer has been one of immense growth and I am excited to continue navigating this exciting world of science.

Throughout BSURF, we have had the opportunity to learn about so many different fields of research and have obtained advice from various faculty members here at Duke. Learning about fields different from my own was incredibly fascinating, and hearing advice from researchers of all different backgrounds was super helpful. 

I was especially intrigued by the research that I had not even thought about before. One example of a talk that especially blew me away was Dr. Sheila Patek’s talk about ultra-fast movements. I had never considered research on the fastest movements on the planet. Dr. Patek first talked about the trap-jaw ant, which closes its jaw to capture prey at a speed of nearly 70 mph. She also talked about the snapping shrimp which has a shooting defense system that is super fast. 

But the main event of her talk was the mantis shrimp, which has an incredibly fast small hammer to break snail shells. The mantis shrimp has peak forces 2500 times its body weight, but somehow manages to not break itself. The smashing motion has likely evolved over time to become one of the fastest motions known. Dr. Patek explained how there are principles underlying this biological diversity that proper industry forward. Material scientists and engineers can use research like hers and apply it to a variety of applications. 

But the one thing that really surprised me about Dr. Patek’s research was the fact that she was faced with much opposition regarding the importance of her research. However, Dr. Patek preserved and worked hard to defend why research like hers is necessary, which I really admire. I was inspired by Dr. Patek to always remember to stand up for your passions and what you believe in, regardless of those who may not agree with you. 

Although dystonia is the third most common movement disorder and causes muscles to contract uncontrollably, the exact mechanisms for dystonia are poorly understood. Past research on multiple forms of dystonia have implicated phospho-eIF2a pathway activity in the brain as a central source of dysfunction. This pathway is involved in responding to cellular stressors and mediating synaptic plasticity responses in the brain. The goal of this study is to identify the brain regions and developmental periods in which the pathway’s activation is disrupted in a DYT1 mouse model of childhood-onset dystonia. Western Blot analysis was used to determine the expression levels of phospho-eIF2a and total eIF2a of DYT1 and control mice at various time points in development including p0, p5, p14, p21 and p30 and in various brain regions including the striatum, cortex, cerebellum, and midbrain to determine where pathway dysregulation was most predominant. This knowledge will advance our understanding of the cellular mechanisms of dystonia and provide proof-of-principle experiments to determine whether targeting this pathway is beneficial.

When working in a lab, it can sometimes be hard to fully understand the clinical applications and practical elements of working on a project long term. This week, while listening to the chalk talks of my peers, Simone’s particularly stood out to me because it was a clinical application of research. I thought it was incredibly fascinating how her research is focused on creating a D4 assay to measure protein biomarkers in blood efficiently. In the past, the most common type of methodology for blood-based diagnostics is ELISA which is an enzyme-linked immunosorbent assay. However, there are a variety of downsides to this system as it requires a large amount of resources, and is not very simple to use. Therefore, Simone’s research is focused on the D4 assay which requires fewer resources and can be used with little user training, making this system much more efficient. 

The whole idea was very cool and her illustrations from her chalk talk truly helped to convey how exactly the machine will work. Special assay reagents are first coated onto a coated glass chip. Then, the sample, either blood or serum is added, which drives the D4 assay chip to completion. In addition, the assay is highly portable. The system has a cell-phone based detector for the sample which uses the camera to readout the fluorescence on the D4 assay, which can in turn detect the protein of interest. 

I also enjoyed taking a step back and looking at how these D4 assays could help provide detection for breast cancer or Methicillin-resistant Staphylococcus aureus (MRSA) using specific assays, which could help with earlier detection and treatment. In the breast cancer assay, she will be targeting a protein called HER2, which is found in breast cancer cells. If the assay is capable of identifying this protein, then the patients can be treated with anti-HER2 drugs, which can be hugely beneficial. There are also other clinical biomarkers that have been associated with breast cancer which Simone will be targeting, which include ER, PR and Ki67. If Simone and her lab can create a D4 assay that targets all of these biomarkers simultaneously, it will be easier to provide better treatment and care for patients. Simone is also studying MRSA, which is important because MRSA can resist antibiotics due to a specific protein called PBP2a. If a D4 assay can be used to detect PBP2a early on, MRSA treatment could become quicker and more efficient. 

Overall, since I wasn’t completely aware of this project, it was very cool to learn about something outside of the basic lab research. This project also helped me to realize that I may want to work on a clinical research project in the future. D4 assays seem to be a major part of the future of diagnostic medicine, and I’m grateful to have had the opportunity to learn about them through Simone’s chalk talk! 

My mentor, Dr. Ashley Helseth, has been a tremendous help in not only guiding me in my research project, but also in helping me to navigate and understand my lab’s research as a whole. She has been incredibly influential and I cannot wait to continue working with her for the rest of the summer and into the future.

Dr. Helseth has definitely had a unique journey in science as she seemingly never stops learning. At the age of 5, she knew she wanted to be a pediatrician. But, as she got older she realized she wanted to become a vet. She spent her undergraduate career as “pre-vet”, but soon realized she had a passion for scientific research. So, she decided to get a pHD at the University of Nebraska Medical Center following her undergrad. During graduate school, she focused on neuroimmunology, but specifically the modulation of the immune system to treat Parkinson’s. One driving reason she decided to do research on Parkinson’s in specific was because she had many family members who had been diagnosed with it and wanted to understand the disease pathology.

However, Dr. Helseth’s journey did not stop after she got her PhD. Her love for learning continued as she was inspired by her PhD mentor to pursue an MD. Dr. Helseth explained that in addition to the obvious job security that comes with being a physician, she realized that the best way to understand the disease is to see the clinical manifestation. She explained how good scientists can take a step back to see the big picture and she found that incredibly fascinating. So, then Dr. Helseth came full circle to her passion from when she was a mere 5 years old. After medical school at the University of Nebraska, Dr. Helseth did her residency in child neurology here at Duke.

Though Dr. Helseth does go to clinic occasionally, she spends a lot of her time in the lab doing research of course. When asked what her favorite part about doing research is, she explained that it is that moment when you obtains a result that contradicts past literature. Dr. Helseth loves the thrill of exciting and unexpected outcomes! However, she also spoke to me about something that she wished to change about the field. She wished for a world in which science was more focused on collaboration, as opposed to competition. She explained how in the physician world, doctors constantly collaborate to obtain the best medical outcome for their patient. She explained how she would like for their to be less of a focus on competing to publish first and more focus on reaching out to others to achieve the end goal of disease treatment.

In addition, despite her busy life, Dr. Helseth explained how it is important to have a balance. Outside of lab and clinic, she enjoys running, hiking, watching movies and of course hanging out with her family. She also offered two main pieces of advice to future students based on her experiences.

1. Don’t be discouraged by failure because it is going to happen.
2. Work should never be your job, but it should be your career. She was explaining how important it to find something you are passionate about, because work won’t feel like “work” if you do!

I’m so grateful to have Dr. Helseth as a mentor and I can’t wait to continue learning alongside her!

We have all had various experiences that have had a significant effect on who we are and how we act. Whether it was the childhood memory we will never forget, or the friendships we formed throughout school, our experiences definitely shape us. In a similar fashion, the neural connections within our brain change in response to experience. Just like when someone makes an impression in clay, our brains’ circuitry changes in response to new experiences.

This idea is referred to as “synaptic plasticity” and is a major focus of the Calakos lab, where I am working this summer. The lab focuses on how experience influences behavior, but also how in neurological conditions, the mechanisms of synaptic plasticity can go awry. More specifically, I am focusing on the condition of dystonia, which is a movement disorder in which muscles may contract uncontrollably and is the third most common movement disorder.

Past research within the lab has shown that there is a specific protein pathway known as eIF2alpha which is associated with synaptic plasticity and may be correlated with dystonia. Think of this protein pathway like a set of instructions that helps regulate our cells. This pathway typically responds when cells are experiencing high stress. It has been hypothesized that in dystonia, this pathway becomes dysregulated early on in development.

However,  it remains uncertain whether and when targeting eIF2α signaling can improve dystonia. It is also important to determine exactly where in the brain selective vulnerability to altered eIF2α signaling occurs. Therefore, for my research project, I will be using western blot to determine if there is a dysregulation in eIF2alpha in a mouse model of dystonia compared to their littermate controls. I will analyze the brain tissue from mice for expression of eIF2alpha at various time-points throughout development including the day of birth, 5 days after birth, 14 days after birth, and 21 days after birth to determine if there is a period of susceptibility in which pathway dysregulation occurs. I will be analyzing four main brain regions: midbrain, striatum, cerebellum and cortex, regions previously implicated in dystonia, to determine if there is a specific brain region in which the pathway’s dysregulation is most predominant. I feel that my experiences working in this lab on this project will definitely shape my future decisions and maybe even change a few of my neural connections along the way.

Day one of BSURF and I was diving in at the deep end with my first lab meeting at the Calakos Lab, where lab members discussed the projects they were working on. I was slightly intimidated by the vast array of jargon, diagrams and graphs that were presented, but at the same time I became even more motivated and excited to learn. As I introduced myself to my new labmates at this meeting, my Principal Investigator asked what I expected from my summer research experience. Put quite simply, I responded, “I want to learn as much as possible and make even a small contribution to the lab.” But let’s further unpack that. 

Prior to this summer, I had never had a serious research experience. Coming to Duke, I knew that research was something I wanted to try, but I wasn’t exactly sure what that meant. One of my primary goals for this summer is to leave with no regrets and ensure that I utilize every possible learning opportunity. Even though right now a lot of scientific research on my topic goes right over my head, I expect to delve into the scientific literature on my project, and hopefully, get a better understanding of what I am trying to accomplish. In my first week alone, I have obtained so many new skills and learned so much from my mentors, but I know that this is just the beginning. I hope that as I gain an understanding of this field, I get a sense if research is something I want to continue throughout the rest of my undergraduate and professional career.

While I obviously don’t expect to find a life-changing discovery over the summer, I do hope to help out in the lab in any way that I can. I hope to establish a good relationship with my mentors and my labmates so that they can count on me to do what I am expected. I want them to know that I am eager and ready to help in whatever capacity that may be. Ultimately, I know that this first week might have been a bit of a steep learning curve as I get acquainted with the lab, but I can’t wait to see what the rest of the summer holds and slowly, but surely learn to navigate this new world of science.

My First Time Doing PCR on my own!