Exploring the Mechanisms and Cellular Specificities of Antifungal Toxins

Fungal toxins are critical to microbial competition and pathogenicity, offering valuable insights into their interactions with fundamental cellular processes and in microbial ecology. This research program investigates the molecular mechanisms of fungal toxin-mediated cell killing, the pathways that govern toxin susceptibility, and the evolutionary dynamics of toxin-target interactions. By integrating molecular modeling, artificial intelligence, evolutionary biology, and biochemistry, the program aims to uncover the determinants of toxin cell-type specificity, with future implications for understanding the molecular mechanisms of protein toxins and fundamental cellular processes in fungi. The investigator has established foundational knowledge of killer toxin diversity, specificity, and mechanisms of action. These studies have identified critical pathways influencing toxin susceptibility, demonstrated the rapid evolution of toxins and their targets, and uncovered novel antifungal activities with potential commercial applications. The investigator’s proven productivity, dedication to mentoring future scientists, and development of innovative methodologies highlight the ability to deliver impactful research while adapting to emerging technologies and evolving questions in killer toxin research. This program will advance our understanding of diverse killer toxins produced by fungi, focusing on their cytotoxicity and interactions with cellular structures. It aims to address key knowledge gaps in toxin function and specificity by developing a rapid toxin characterization pipeline. The program will also use the Saccharomyces K1 toxin as a model to investigate its structural homology with other toxins, explore its interactions with fungal cells, and examine the evolution of resistance, mainly through changes to the fungal cell wall and membrane. This research will enhance our understanding of resistance mechanisms evolved by fungi in response to external stressors and open new avenues for antifungal strategies targeting opportunistic fungal pathogens. Project Number: 1R35GM161960-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Paul Rowley | Institution: UNIVERSITY OF IDAHO, MOSCOW, ID | Award Amount: $426,404 | Activity Code: R35 | Study Section: Special Emphasis Panel[ZRG1 MBBC-J (55)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11260778