César de la Fuente
University of Pennsylvania
Artificial Intelligence Approaches for Antibiotic Discovery
2023 Rao Makineni Lectureship
Monday, June 26, 2023, at 12:15 pm - 12:45 pm
Artificial intelligence, AI, has the potential to outperform humans and revolutionize our world. In this talk, I will describe our efforts using AI to develop computational approaches for antibiotic design and discovery.
Computers can already be programmed for superhuman pattern recognition of images and text. In order for machines to discover novel antibiotics, they have to first be trained to sort through the many characteristics of molecules and determine which properties should be retained, suppressed, or enhanced to optimize antimicrobial activity. Said differently, machines need to be able to understand, read, write, and eventually create new molecules.
I will discuss how we trained a computer to execute a fitness function following a Darwinian algorithm of evolution to select for molecular structures that interact with bacterial membranes, yielding the first artificial antimicrobials that kill bacteria both in vitro and in relevant animal models.
My lab has also developed pattern recognition algorithms to mine the human proteome, identifying throughout the body thousands of antibiotics encoded in proteins with unrelated biological function, and has applied computational tools to successfully reprogram venoms into novel antimicrobials.
Computer-generated designs and innovations at the intersection between machine and human intelligence may help to replenish our arsenal of effective drugs, providing much-needed solutions to global health problems caused by infectious diseases.
César de la Fuente is a Presidential Assistant Professor at the University of Pennsylvania, where he leads the Machine Biology Group, whose goal is to combine the power of machines and biology to help prevent, detect and treat infectious diseases. Specifically, he pioneered the development of the first antibiotic designed by a computer with efficacy in animals; designed algorithms for antibiotic discovery; reprogrammed venoms into antimicrobials; created novel resistance-proof antimicrobial materials and invented rapid low-cost diagnostics for COVID-19 and other infections.
De la Fuente is an NIH MIRA investigator and has received recognition and research funding from numerous other groups. He has received over 50 awards. He was recognized by MIT Technology Review as one of the world’s top innovators for “digitizing evolution to make better antibiotics.” He was selected as the inaugural recipient of the Langer Prize, an ACS Kavli Emerging Leader in Chemistry, and received the AIChE’s 35 Under 35 Award and the ACS Infectious Diseases Young Investigator Award. In 2021, he received the Thermo Fisher Award and the EMBS Academic Early Career Achievement Award for “the pioneering development of novel antibiotics designed using principles from computation, engineering and biology.” Most recently, Prof. de la Fuente was awarded the prestigious Princess of Girona Prize for Scientific Research, the ASM Award for Early Career Applied and Biotechnological Research, and was named a Highly Cited Researcher by Clarivate.