Colloquium with Presidential Assistant Professor César de la Fuente of the Perelman School of Medicine

Title: Towards Computer-Made Antibiotics

Until now, the natural world has supplied us with antibiotics. Bacteria, however, are increasingly resistant to these drugs. The next generation of antibiotics will likely come not from nature but from computer-based discovery. Working at the forefront of this development, I seek to harness computational power to find molecules with antibacterial activity. I use synthetic biology and computational tools to determine features contributing to this activity and train computers to find— or design— candidate molecules and tweak their structures virtually. Experimentation is reserved for validating computer predictions, saving time, labor, and expense. With machine-based molecular discovery, I explore proteins and peptides as engineering scaffolds. My approaches diversify proteins, such as host defense peptides (HDPs), beyond their natural variation. For example, to increase their antimicrobial properties, we trained a computer to execute a fitness function that selects for structures that interact with bacterial membranes, thereby converting several HDPs into the first artificial antimicrobials that kill bacteria both in vitro and in animals. By investigating these exciting possibilities, I aim to build machine-made antibiotics to combat infectious diseases and develop clinical applications for autonomously generated synthetic molecules. Computer-made drugs may help to replenish our arsenal of effective drugs and outpace the evolution of antibiotic resistance.

Biography

César de la Fuente, Ph.D. is a Presidential Assistant Professor at the University of Pennsylvania, where he is leading the Machine Biology Group to integrate synthetic biology, microbiology, and AI. Prof. de la Fuente seeks to expand nature’s repertoire to build novel synthetic molecular tools and devise therapies that nature has not previously discovered. The Machine Biology Group aims to develop computer-made tools and medicines that will replenish our current antibiotic arsenal. Prof. de la Fuente was named a Boston Latino 30 Under 30, a 2018 Wunderkind by STAT News, a Top 10 Under 40 of 2019 by GEN, a Top 10 MIT Technology
Review Innovator Under 35 (Spain), and is a recipient of the 2019 Society of Hispanic Professional Engineers Young Investigator Award. He has also been recognized by MIT Technology Review in 2019 as one of the world’s top innovators for “digitizing evolution to make better antibiotics”. In 2019, de la Fuente was selected as the inaugural recipient of the Langer Prize. His scientific discoveries have yielded over 70 peer-reviewed publications and multiple patents.