Chemical and Biological Engineering PhD student Max Yavitt is the lead author on a new paper in Science Advances that focuses on intestinal tissue research. The work could allow researchers to control the shape of intestinal tissue cultured outside of the body – allowing for better study of physical changes due to injury or illness.
We asked Yavitt about the work, his time at CU Boulder and where the research will go from here.
Question: What is your department and area of study? What do you plan to do after graduation with your PhD?
Answer: I am a sixth-year PhD candidate in the Department of Chemical and Biological Engineering, and I plan to graduate at the end of this semester – hopefully. I’m in the process of looking for jobs right now, but I hope to work as a research and development scientist for a biotech company in the field of biomedical devices, biomaterials, or tissue engineering.
Q: How would you describe the work and results of this paper?
A: The intestine is composed of a single layer of cells that are organized into regularly repeating features in three dimensions, known as crypts and villi. Villi protrude out into the open intestinal lumen, while crypts depress into the tissue that surrounds the intestine, creating a sort of wavy surface that can compress or stretch cells that are distributed along different regions. These physical forces can change the behavior and function of a cell, but that has been difficult to study inside of the body.
In this work, we design a material that enables the researcher to control the shape of intestinal tissue cultured outside of the body. This will allow for closer study of how physical changes in stretching, cell shape, and curvature affect intestinal cellular behavior – specifically the formation of intestinal crypts I mentioned before. In this research, we found that intestinal cells can sense when they are exposed to regions of curvature, and we identified a biological pathway that cells use to initiate crypt formation events.
Q: What are the applications in the real world from this research?
A: Stretching and compression are prevalent during intestinal homeostasis, which is just regular intestinal function. However, forces and cell shape undergo dynamic changes during the development of the intestine in pregnancy and early childhood and following intestinal injury. In this work, we designed a material platform to understand how physical forces regulate crypt formation. The goal is to this platform to better understand how the intestine develops or recovers from injury for example. That could lead to the design of drugs or therapeutics to help when something goes wrong, such as in the case of intestinal disease.
Q: Is this a research topic or area you were interested in before coming to CU Boulder?
A: Before coming to CU Boulder, my undergraduate research had focused on the use of biomaterials as drug delivery devices, from which I developed a general interest in using biomaterials to address medical challenges. However, I was unaware of the issues facing intestinal tissue engineering specifically. Part of the reason that I was interested in CU Boulder was because I would be exposed to many new applications. Other people in the Anseth Lab design biomaterials to study heart disease, muscle regeneration, or cancer progression, so I knew that there would be plenty of interesting opportunities to address unique medical challenges.
Q: What research questions are still to be answered after this paper? Where does the work go from here?
A: This paper helps to understand how physical forces can guide early crypt-forming events, which is important to consider during intestinal development or following injury. From an engineering perspective, we can use our material platform and the information we have learned about the driving biological mechanisms, to now control intestinal development in a deterministic manner. In the next steps, we will exploit these principles to make intestinal tissue that has the same size and shape, to make more reproducible cellular models for applications such as drug screening.
Q: Anything else you want to say about your time at CU Boulder or working with Professor Kristi Anseth?
A: I have had a great time working at CU Boulder over the past six years. Doctor Anseth has been a supportive mentor and has taught me how to be a better scientist and engineer. I am excited to move on to the next phase of my life, but I will miss my time here at CU Boulder!
“In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis” was supported in part by the National Institutes of Health (R01 DK120921, P30-DK116073, P30-CA046934, F31 DK126427, R01 GM072744, and P30 NS048154), DARPA (W911NF-19-2-0024), the National Science Foundation (RECODE 2033723), the Department of Education Graduate Assistance in Areas of National Need Fellowship and University of Colorado Boulder Biological Sciences Initiative. Other CU Boulder authors include Bruce Kirkpatrick, Michael Blatchley, Kelly Speckl, and Kristi Anseth.
Max Yavitt