The effects of Polycystic Kidney Disease (PKD) are astounding. Kidneys, normally the length of a baseball, can grow to be the size of a football with fluid filled cysts covering the entire organ. Oftentimes, the disease can cause heart failure. This summer in Dr. Thomas Weimbs’ lab at the University of California, Santa Barbara, I researched one of the pathways that this disease affects. Specifically, a process called macroautophagy is necessary for kidneys to function properly. In macroautophagy, cells designate and target specific organelles or molecules to be broken down, send a structure to surround them, and then subsequently degrade the organelle or macromolecule (Johansen & Lamark, 2011). Yet in PKD, this process does not occur as it normally would in a healthy individual (Zhu, Sieben, Xu, Harris, & Lin, 2017). This dysfunctional pathway, among others resulting from the disease, results in kidneys that cannot function normally to remove waste from the blood and body. I am looking into what could regulate this decrease in autophagy. Is it the overexpression of a specific protein? And if so, what treatments mitigate this effect? Though this may seem to be a small part of the disease as a whole, it is important to understand the individual mechanisms and pathways within the disease to find new and effective therapies.

Realities of Research

Beginning this project was daunting. There is an incredible wealth of knowledge and research concerning Polycystic Kidney Disease that I had never been exposed to; I needed to look into these topics and understand background information so I could critically think about my project. Initially, reading scientific papers on this topic was very time consuming – I looked into every pathway, gene, and protein that I didn’t recognize in the literature. But slowly, this process became easier, and the topics became more familiar. Now, 10 weeks later, I am more confident in my ability to read and understand the scientific literature that is closely related to this topic.

I am also more comfortable with the hands-on lab techniques that I explored and focused on during my research internship. Specifically, I dedicated many weeks to microscopy, a technique that I had not ever been extensively exposed to. I find it incredible to look at the cells that I cultured and treated with different drugs, plasmids or antibodies up close. And though I didn’t expect it, I actually find the photos that result from my immunofluorescence experiments quite beautiful – I think they look like multi-colored galaxies.

These past 10 weeks have been both enlightening and frustrating at the same time – but mostly they have been rewarding. Though it was disappointing to have experiments that I spent over a week preparing yield no results, it was even more exciting when I did see results for the first time. I’ve learned the value of patience in the lab and careful, meticulous work. I’ve learned how important it is to put in outside work to reap the benefits of the environment you are in. And lastly, I’ve learned to not give up if something does not work. Instead, I analyze why it happened, and try again.

This summer has exposed me to a new and exciting realm of biology. I am incredibly grateful for the opportunity to have been connected with new peers and mentors, and to make a little dent in a very big and profound research topic.

References

1. Johansen, T., & Lamark, T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 7(3), 279–296, 2011.
2. Zhu, P., Sieben, C. J., Xu, X., Harris, P. C., & Lin, X. Autophagy activators suppress cystogenesis in an autosomal dominant polycystic kidney disease model. Human Molecular Genetics 26(1), 158–172, 2017.

Madeline Matthys is a senior at Duke University in Durham, NC . She is majoring in Biology and minoring in Chemistry. With the generous help of the American Physiological Society through the Undergraduate Summer Research Fellowship program, Madeline worked in Dr. Thomas Weimbs’ lab at the University of California, Santa Barbara in Santa Barbara, CA. Madeline plans to continue biological research and after she receives her Bachelors of Science, she hopes to attend medical school.