Design of Programmable Biologics with Discrete Generative Algorithms
The Chatterjee Lab at the University of Pennsylvania develops generative algorithms to design functional biologics directly from sequence. Our work has centered on protein language models that de novo design peptides to bind and modulate undruggable disease targets, with experimental validation across rare neurodegenerative disorders, pediatric cancers, and viral infections. However, because therapeutic design depends not only on binding but also on developability, specificity, and cellular context, we have developed new discrete diffusion modeling algorithms to generate peptides, proteins, mRNAs, and isoform-specific modulators, enable controllable, Pareto-efficient generation. We have extended further to discrete flow-based generative models to refine highly specific, domain- and motif-resolved binders under competing objectives. Beyond therapeutics, we have also applied our discrete generative frameworks to metal-binding peptides and environmental toxins for bioremediation applications. Finally, we’ve recently pioneered a new class of generative models, termed Schrödinger Bridges, that not only model biological states but also the trajectories connecting them, from protein folding to cell-state transitions, establishing a unified and programmable framework for molecular design grounded in physics and context-aware dynamics.
Bio: Pranam Chatterjee is an assistant professor of bioengineering and computer and information science and the Africk-Lesley Distinguished Scholar of Innovation at the University of Pennsylvania. His Programmable Biology Group develops new discrete generative models for the de novo design of biologics, spanning from algorithmic theory to pre-clinical validation in vitro and in vivo. The lab specifically develops therapeutics for rare pediatric diseases, infertility, and substance use disorders, as well as molecules for environmental bioremediation. Having earned his S.B., S.M., and Ph.D. from the Massachusetts Institute of Technology, Chatterjee has received the MIRA Award, Hartwell Individual Biomedical Research Award, and multiple NIH and foundation grants for his work. He has also co-founded Gameto, Inc., UbiquiTx, Inc., AtomBioworks, Inc., and Recognition Bio, Inc., which translates his research into fertility-related solutions, RNA medicines, and cancer therapeutics, respectively.