CHARACTERIZING NOVEL PEPTIDES FROM THE HUMAN MICROBIOME

Abstract

The human microbiome is a source of compounds that can impact human health and wellbeing. These compounds, in the form of small molecules, peptides, and proteins, participate in microbe-microbe and host-microbe interactions. In this thesis work, I sought to characterize small peptides from the microbiome. While recent work has identified thousands of small peptides, there is a lack of systematic evaluation of bioactivity. To gain a better understanding of the bioactive peptide space, I apply functional and cheminformatic approaches and follow up with targeted bioassays.In the thesis presented here, I describe approaches to uncover and characterize microbiome-derived peptides. I show that the gut microbiome encodes a peptide that aligns to a known sporulation peptide, and that this peptide has antimicrobial activity. Next, I delineate a pipeline that helped determine that a novel, secreted small peptide can be a protease inhibitor. I also present my work as a Science, Technology and Environmental Policy Fellow where I specialized on the topic of antimicrobial resistance. I provide a basic, speculative revenue projection for a drug market and then examine the antimicrobial resistance issue through a national security lens. I review the current innovative and strategic approaches at federal agencies to countering antimicrobial resistance. I then provide a list of fifteen policy proposals. It is my hope that this body of work can contribute to the understanding of the compounds produced by the human microbiome and their molecular roles in microbe and host interactions. I also hope that my work in science policy can serve as a springboard for policies and programs that directly impact society and secure our future health.