Faculty supervisor: Dr. Andreas Matouschek
Name of project: Characterizing substrate selection by the 26S proteasome
Please give a brief, simplified overview of your research project.
The 26S proteasome is the primary machine that controls degradation of damaged and misfolded proteins. Substrates are targeted to the proteasome through ubiquitin tags, and degradation is initiated at an unstructured region, or tail, within the substrate. The geometry of the substrate plays an integral role in substrate selection. Substrates with optimal geometries have the unstructured region reach into the proteolytic pore of proteasome which results in affective degradation. Substrates with poor geometries have unstructured regions that do not reach the proteolytic pore which leads to little to no degradation. Substrates were made with varying alpha-helix spacers, from 0 amino acids to 70 amino acids, between the ubiquitin tag and initiation tail in order to test which geometries are affectively degraded by the proteasome. Degradation was measured by detecting fluorescence from a fluorescent domain that is within each substrate. The results showed that degradation of the model substrates depend on the geometry of the substrate where optimal degradation peaked at the alpha-spacer with 30 amino acids.
Describe the tasks you engage in as part of your work.
• Plasmid cloning
• Protein purification
• In-vitro fluorescence based degradation assays
Describe what you thought college might be like before you came to UT. Did you consider research when thinking about college?
I honestly thought that during college, all I would have time to do is study for my classes. I didn’t know that UT would provide such a wide variety of extracurricular activities that would enhance my learning experience. Because I was interested in STEM, I knew that I would either like to go into research or healthcare, so research was always on the table for me.
How did you get involved with your research project?
I took Dr. Matouschek’s biochemistry course and on the first day of class he mentioned the kind of research he was doing. It sparked my interest so I did a little more research on his lab and emailed him about a potential position in his lab. Fortunately, we sort of clicked and I’ve been working in his lab for about two years
now. Based on some previous research I did, Dr. Matouschek decided to put me on my current project.
Do you see your project connecting with your plans for your future?
I will always be interested in the proteasome, however what I learned from working in the lab was how to think through problems. I think this skill can be applied to anything I do, whether or not it is research related.
What is the most interesting or surprising thing you’ve gotten to do for this project?
A few weeks ago in February, my PI flew me out to Washington, D.C. where I got to present my work at a national conference called the American Association for the Advancement of Science (AAAS). I competed in a poster competition where I was against undergraduates and graduate students from all across the nation. As it turned out, I won the molecular and cellular biology section that had about 90 other presenters. It was so surprising to know that other researchers understand the importance of my research which is easy to forget sometimes.
What advice would you give to a student who was thinking about research?
I would say that even if you are curious about research, try it out. You will never know how you feel about it until you are actually doing it. I would also say be persistent. If you reach out and don’t hear back, follow up. If you get rejected from a lab, look for another one. You probably won’t find the perfect lab for you on the first try, so keep your head up and your options open.