Talia Nguyen Rose Hills
Suppression of NOD2 Signaling During Listeria monocytogenes Infection
Listeria monocytogenes (Lm) is a Gram-positive facultative intracellular pathogen and model organism used to study bacterial pathogenesis and host immunity. Hosts recognize bacteria and signal immune responses in part by activating the cytosolic receptor NOD2 with a small molecule (MDP) derived from bacterial cell wall peptidoglycan. However, our preliminary research shows that NOD2 is not activated in vivo, despite Lm cell growth and division releasing MDP and related agonists (e.g., GMDP). This suggests that Lm may secrete an unknown factor inhibiting NOD2 activation, thereby attenuating this pathway in vivo.
My project aims to identify genes in the Lm genome that contribute to this inhibitory effect by screening for mutants in which NOD2 activation is restored following gene disruption via transposon mutagenesis. After sequencing these strains and generating clean mutations, I will validate their phenotypes in WT and NOD2-deficient backgrounds to determine whether the disrupted genes encode for factors inhibiting NOD2 activation. Identifying such factors may inform the design of vaccine adjuvants by showing how NOD2 signaling can be modulated in various physiological contexts.
Message To Sponsor
Thank you so much for your generous support of my summer research project! As an incoming senior planning to pursue a PhD, this opportunity allows me to continue developing the skills and perspective that will guide my future in science. Through this work, I hope to contribute to a deeper understanding of host-pathogen interactions and help inform future approaches to vaccine design.