Tag Archives: asthma

Take My Breath Away- A Summer of Asthma Research

Research Project

Pathology of asthma.

This summer I had the pleasure of working with Dr. Silveyra and her research team at the Penn State College of Medicine investigating the mechanisms behind adult asthmatic females being more susceptible to air pollution than males. Research has shown that upon exposure to an air pollutant like ozone, females that already have a respiratory disease, such as asthma, are much more likely to develop worsening asthma as well as other respiratory problems. I believe this study is very important in today’s world, where the majority of ozone can be found in cities and industrialized areas that have very high populations. Therefor a female with asthma living in a populated city risks the possibility of her asthma worsening or developing other complications.  When people think of asthma, they usually think of shortness, of breath, trouble breathing, and wheezing. These symptoms are all due to a person’s airways becoming inflamed and an air pollutant like ozone could trigger this. The body expresses proteins called cytokines and when certain types of these cytokines are expressed, they can lead to inflammation like we see in asthma. In recent years a special type of RNA called microRNA (miRNA) has been found to play a key role in regulating the expression of these inflammatory cytokines. My research team and I were particularly interested in miR-712, which is a miRNA known to play a role in regulating inflammatory cytokines. Our idea was that if this miRNA is expressed differently between males and females, this could explain why asthmatic females are more susceptible to air pollutants than males.  This study could lead to the development of treatments specific for males and females.

Realities of Research

This was the first real research project I had ever participated in, so it was pretty intimidating in the beginning. However, as time went on I learned new techniques and began to understand the project and why it was important and that got me really excited to be doing research. The part that surprised me the most is how things that are so small like miRNA can play such a huge part in disease and keeping us healthy. Along the way I had to learn new techniques like how to extract the miRNA’s and how to determine how much was being expressed. In the end the results were a little surprising. Yes, we saw higher levels of miR-712 expressed in asthmatic females that had been exposed to ozone, but we also saw even higher levels of it in asthmatic males that had been exposed to ozone. This may have been due to the fact that male mice typically react quicker to the asthma model we used and that it may take females longer to actually “develop” asthma. I think in the future this model may need to be changed a little bit, but that is all a part of doing research.

Life of a Scientist

I found day-to-day life in the lab to be very exciting. There was always something to be doing and it was nice to know that everything you were doing in a day was for a purpose. One thing that surprised me was how long some procedures can actually take. Procedures I would read about in textbooks always seemed like they were quick and then you have your results, but there is actually a lot of hours that go into some procedures. The worst part was exposing the mice to ozone, because it was a three-hour long exposure and it would get pretty boring. The absolute best part was getting to work with my research team. Every single one of them was so helpful and knowledgeable and I am so grateful for them.

 

Citations

  1. Fuentes, N., Roy, A., Mishra, V., Cabello, N. and Silveyra, P. (2018). Sex-specific microRNA expression networks in an acute mouse model of ozone-induced lung inflammation. Biology of Sex Differences, 9(18).
Ashley Weaver is a rising senior at Penn State University in State College, Pennsylvania majoring in immunology and infectious disease. She is a 2018 Short-Term Research Education Program to Increase Diversity in Health-Related Research (STRIDE) fellow working in Dr. Patricia Silveyra’s lab at the Penn State College of Medicine in Hershey, Pennsylvania. Her fellowship is funded by APS and a grant from the National Heart, Lung, and Blood Institute (Grant #1 R25 HL115473-01). 
After graduating, Ashley plans to pursue a career in clinical lab work for government organizations and then to pursue her masters in immunology.
More Than a Powerhouse

Over the summer, I have been conducting research in Dr. Sathish Venkatachalem’s lab at North Dakota State University. Our lab investigates the effects of sex steroid hormones such as estradiol on asthma. Asthma currently affects 1 in 13 people in the United States and results in 14.2 million doctor’s office visits each year.1 In recent years it has been discovered that pre-menopausal women have a higher rate of asthma than men, suggesting a role of hormones (a chemical secreted from glands) in asthma.2 While men have a small amount of estradiol secreted into their bloodstream, pre-menopausal women have much more estradiol which helps to regulate the menstrual cycle among other functions. My project focuses on how different hormones in men and women could have an impact on asthma. My focus is specifically on a specialized structure in cells called mitochondria. Mitochondria are largely known for converting energy into a usable form of adenosine trisphosphate (ATP), but they also play many other roles. For example, mitochondria act as a reservoir for calcium within the cell which is important because calcium is an essential component of contraction, cell signaling, and nerve cell function, among other roles. My hypothesis is that if mitochondria are not functioning properly to buffer calcium, they cannot help with calcium regulation which may cause more contraction in the muscle cells surrounding the lung airway. As a result, the airway could narrow, and breathing could become difficult if not impossible. My project investigates how mitochondria change shape in asthmatic conditions and whether they are working together as a team to regulate calcium in cells. It is crucial for mitochondria to buffer calcium so that proper contraction and relaxation of the lung airways can occur. Proteins called Drp1 and Mfn2 regulate the fusion and fission process between mitochondria and are key in my investigations into mitochondrial morphology. Fusion proteins cause mitochondria to bind together, while fission proteins cause mitochondria to break apart. If too many fission proteins are present in mitochondria it can result in increased breakage and the failure to properly buffer calcium. In the future, mitochondria could be a target for treatment of asthma to reduce contraction and allow a patient to breathe more easily.

 

Image of mitochondria.

Research is quite different from other punch-in punch-out jobs I have had. Often, experiments demand that you come early or stay late to get results. I have been fortunate to work under a graduate student who has helped me prioritize which experiments need to be done and at what time. Through the summer, I have come across quite a few challenges and I have found that my critical thinking skills have been sharpened because of it. For example, at the beginning of the summer I was trying to identify a certain protein within my mitochondria, but it proved to be elusive at first. Through trial and error, I modified the protocol of the experiment until proper results were obtained. During those weeks, I felt discouraged because it was not exciting to repeat the same experiment multiple times over. However, I learned to problem solve through scientific protocols and I grew as a researcher because of it. The part of my project that I have found the most rewarding is taking images of my mitochondria. Results come quickly because the mitochondria absorb a dye quickly, then they light up under my microscope. I have learned to view the pictures of those mitochondria as art; the bright green squiggles that show up on the imaging screen never fail to amaze me and remind me of what I can do in this field.

 

Christy pictured in Dr. Sathish Venkatachalem’s lab at North Dakota State University.

Being a scientist in a lab for ten weeks has revealed to me the need for creativity in science. When I did not know how to proceed with an experiment or a result, I had to think outside the box, ask other scientists, or modify the protocol. Some days were exciting because the data turned out very well after many days of work. Other days were packed with processing mitochondrial data in front of a computer. I really enjoyed that my day-to-day experience in the lab was constantly changing due to the different experiments that I had the opportunity to run. I was also surrounded by brilliant scientists and colleagues that were willing to explain a finding to me or sharpen my skill at a certain technique in the lab. I have learned that science needs to be collaborative because many minds combined are better than one. I am grateful to the American Physiological Society for the opportunity to learn these lessons during ten weeks of research this summer.

 

References:

  1. (2018, April 24). Retrieved from https://www.cdc.gov/asthma/default.htm
  2. Sathish V, Martin YN, Prakash YS. Sex steroid signaling: implications for lung diseases. Pharmacology & therapeutics. 2015; 150:94-108.
  3. (2015, April 26). [Image of mitochondria]. Retrieved from https://www.bbc.com/news/health-32434347
Christy Jesme is a senior at North Dakota State University in Fargo, ND. She is majoring in biology and minoring in chemistry and psychology while working in Dr. Sathish Venkatachalem’s lab. The lab investigates the role of sex steroid signaling on asthma. During the summer of 2018, Christy was awarded the Undergraduate Summer Research Fellowship funded by the American Physiological Society. She is currently in the process of applying to medical school in hopes of attending classes in the fall of 2019.