Discipline: Biological Sciences
Subcategory: Chemical/Bimolecular/Process Engineering
Session: 4
Room: Exhibit Hall
Tyrece Emeil Frater - University of South Florida
Co-Author(s): Dr. Laurence A. Stern, University of South Florida, Florida
Interleukin(IL-4) is a cytokine that initiates type 2 helper-T cell pathways and mediates lymphocyte differentiation. Interleukin-4 is prized for its ability to suppress pro-inflammatory responses. Interleukin-4 is not a heavily engineered protein despite its notable impact in relieving autoimmune diseases such as psoriasis (Yang et. Al). Our approach to interleukin-4 was to increase its affinity for interaction without jeopardizing its stability. If we can increase the ligand’s affinity for interaction, then we can engineer a mutant IL-4 that will relieve these autoimmune diseases to a greater extent. We ran a command called Analyse Complex to understand the thermodynamic values that constitute interleukin-4. These values are important because it is no use to engineer a brilliant protein that cannot withstand the body’s internal environment. We ran two commands called Position Specific Scoring Matrix(PSSM) and Build Model. These commands applied mutagenesis to interleukin-4’s ligand, and receptor. Position Specific Scoring Matrix mutated the amino acids on the ligand that interact with the receptor. Build Model mutated the thermodynamic values of the non-interacting amino acids found on the receptor. After mutation, the thermodynamic values of a protein change, as did ours. We used this data to create heat maps in Microsoft Excel that allowed us to target segments of our cytokine that are suitable for bioengineering. Our heat map results from PSSM suggest that we may not be able to improve IL-4’s affinity for interaction without compromising structure. Our results from Build Model suggest that there are many mutations that we can make to IL4’s non-binding interface to improve its potency as a therapy for autoimmune diseases. Collectively, our results provide great incentive for further research.
Funder Acknowledgement(s): This research was funded by the National Science Foundation Research Experience for Undergraduates program Award Number 1950458. This opportunity was possible because of the work of LSAMP senior specialist Mr. John Fynn. This research is supported through a grant from the National Science Foundation under the Louis Stokes Alliances for Minority Participation (LSAMP) Program, HRD-1712683, 2017-2020.
Faculty Advisor: Dr. Laurence A. Stern, sternl@usf.edu
Role: I completed the entirety of this research with the verbal guidance of my professor, Dr. Lawrence A. Stern.