Alec Buttner ’21
Synthesis of Peptide-Based Quorum Sensing Modulators for S. pneumoniae
Major: Biochemistry
Hometown: Easton, PA
Project Advisor: Dr. Bertucci
Briefly describe your project.
Streptococcus pneumoniae is a pathogenic bacterium that is the cause of many health issues such as bacterial infection, pneumonia, and sepsis. The ability of S. pneumoniae to infect a host organism (i.e. humans) is largely controlled through quorum sensing. Quorum sensing is a cell-density dependent form of bacterial communication where bacterial cells release a signaling pheromone once a population density is reached. Through Solid Phase Peptide Synthesis (SPPS), synthetic variants of the competence stimulating peptide (CSP1), one of the main signaling pheromones in S. pneumoniae are made. These synthetic peptides include substitutions in the native CSP1 sequence that increase binding efficiency to the quorum-sensing receptor (ComD1), but include a mutation in the first position that turns the peptide from an activator to an inhibitor for the quorum-sensing circuit. This results in decreased quorum-sensing in S. pneumoniae and, thus, lower levels of virulence and infectivity.
Describe the origin of your project.
During the fall of my Sophomore year, I approached Dr. Bertucci about his research as I found the projects very interesting. After discussing the details of the projects, Dr. Bertucci presented the opportunity for me to work in his lab. I worked with Dr. Bertucci throughout the Spring semester of my Sophomore year and applied for the SOAR program with Emilee Engler, another student who collaborated with me on the research project.
What’s the best part about working with your faculty mentor? What valuable insights have they brought to your project?
Dr. Bertucci encourages us to take control of the project and contribute to decisions about the project’s direction (i.e. what CSP1 variants to make and why). Instead of simply carrying out laboratory procedures, he encourages us to look at our data critically to make scientific decisions about our research. This has helped me understand the scientific process and how research projects develop over time.
What has been your biggest obstacle so far?
The biggest obstacle for myself was learning all the facets of our research project. There are so many factors to consider when making amino acid substitutions such as their effects on binding and helicity. Throughout SOAR, Dr. Bertucci worked with us to read through various publications so that we could better understand why our research is taking place, what the overall goals are, and how we can use our knowledge of peptide chemistry to achieve these goals.
What has been your biggest takeaway from this experience?
When looking for research projects, I wanted to find a project that I was passionate about as well as an advisor that would help me gain confidence in a laboratory setting. Throughout SOAR, I was able to make contributions toward research that was meaningful to me, but also develop a skillset that was transferable to other laboratory spaces. I now feel much more confident with lab work and making the critical decisions that come with it.
What was the result of your project?
Some of the substitutions we made greatly improved the binding efficiency of CSP1, which is very useful in the development of a synthetic CSP1 variant that would be used to inhibit quorum sensing. This is important because we want our synthetic peptide to bind more efficiently and outcompete the native peptide, lowering quorum sensing.
In your own words, how do you feel about being awarded this opportunity? Why should other students take advantage of the SOAR program at Â鶹¹û¶³?
I feel incredibly grateful for this opportunity as it has provided me with the ability to develop skills that are useful for the professional world, learn more about concepts within my area of study that are not part of traditional course curriculum, and gain confidence in laboratory settings. I would encourage all students from all disciplines to apply for SOAR and take advantage of this amazing program. Whether you’re an art major, business major, or chemistry major, there is a place for you in SOAR and valuable skill for you to gain through the SOAR program.
Now that SOAR is over, do you plan to expand upon your research? If so, how?
We will continue to make more substitutions and inhibitory peptides using the results from this summer. We will work to increase the binding efficiency as much as possible in order to make the most effective inhibitory peptides for quorum sensing in S. pneumoniae as possible.
Have you, or do you plan to present this research outside the SOAR presentations?
I plan to present our research at Student Scholarship and Creative Endeavors Day, the upcoming ACS conferences, and whatever opportunities are presented to us.