The epithelium is a layer of cells that separates the inside of the human body from the external environment. In the gastrointestinal (GI) tract, these cells are known as enterocytes and must form a barrier against harmful pathogens present in the gut lumen, while at the same time aiding in the digestion and absorption of nutrients. It is important that all these functions of the epithelium are tightly controlled to maintain homeostasis. Dysregulation of these complex processes has been shown to lead to diseases such as inflammatory bowel diseases (IBDs) which affect over 1 million US residents (Kaplan, 2015). IBDs, which include Crohn’s disease and ulcerative colitis, are characterized by chronic inflammation of the GI tract leading to abdominal pain, weight-loss, fever and a loss of quality of life. While the exact cause of the disease remains incompletely understood, we know that the integrity of the barrier of our GI tract is crucial in IBD prevention (Martini, Krug, Siegmund, Neurath, & Becker, 2017).
At a young age, we are often told to eat our vegetables and that fiber is good for our digestive health, but what does that entail? Recently, we have shown that a dietary fiber known as rhamnogalacturonan (RGal) enhances gut barrier function. Furthermore, we have shown that RGal decreases disease severity in a mouse model of colitis. However, how RGal improves intestinal barrier function remains incompletely understood. My project over the summer aimed to characterize the mechanism through which RGal enhances epithelial barrier function. Specifically, my project aimed to evaluate the role of intracellular proteins known as protein kinase Cs (PKCs) in the modulation of barrier function in an intestinal epithelial cell line in response to RGal. Our lab used an apparatus called the Ussing Chamber to measure epithelial barrier permeability. In my project, I will treat my cells with various chemical inhibitors of PKCs in Ussing Chambers and then determine barrier permeability to small ions in response to RGal. If PKCs are involved in the modulation of barrier permeability in response to RGal, chemical inhibition of PKC will block the beneficial effect of RGal on barrier function. By understanding signalling pathways that enhance barrier function in inflammatory diseases in the GI tract, we have the potential to use dietary fibers such as RGal to leverage these pathways to treat active IBD.
There are two realities of research that I was able to experience this summer. First, I think one of the most rewarding things about my research is that we sometimes did not obtain the results that we expected to. Although this may seem counterintuitive, unexpected results in my project were always the most interesting because I was not only able to observe my supervisor’s stunned reaction, but those results were the ones that allowed us to come up with an alternative hypothesis and steer the project in a completely different direction than we initially planned. I think that the experiments that generate unexpected results are my favorite thing about science. Secondly, I think that the most important thing for people to realize about the day-to-day lives of scientists is that finding the cure for cancer or any other major disease does not happen every day. While understanding the bigger picture in the context of a particular disease and the rationale behind the experiments that we conduct is important and keeps us focused, the things that we study day-to-day often involve understanding the physiological role of a particular cellular protein or defining a cell signalling pathway. Although learning cell signalling pathways may sound a little less exciting than curing cancer, a single cell signalling experiment contributes to the overall body of knowledge which eventually leads to the development of a therapy.
This summer, I was incredibly fortunate to work with the people that I did. First, my supervisors Dr. MacNaughton and Dr. Baggio really allowed me to discover my passion for science. Every day, I am able to see their excitement about my work and their devotion to educating the next generation of scientists. Secondly, my lab mates were some of the most knowledgeable, supportive, and enthusiastic scientists that I know. Five years from now, I will not only remember the science from this summer, but I will still remember our debates about fruit with meat in salads, our arguments about whether or not the word ‘meth’ should be allowed in Scrabble (it shouldn’t), our common frustrations about failed western blots and our disagreements about how to pronounce words like ‘drama’ or ‘garage’.