Organic Seminar - George Burslem
Nov
3
2025
Description
The Organic Seminar Series presents: George Burslem
University of Pennsylvania
Host: Ken Hsu
Title: Chemical Tools to Edit Protein Sequences and Post-Translational Modifications
Location: WEL 2.122
Refreshments served at 3:15pm
The ability to study proteins in a cellular context is crucial to our understanding of biology. In this presentation, I will discuss our recent technology development projects to empower the biomedical research community. First, I will describe a new technology for “intracellular protein editing”, drawing from intein-mediated protein splicing, genetic code expansion, and endogenous protein tagging. This protein editing approach enables us to rapidly and site specifically install new sequences, residues or chemical probes into a protein of interest. We demonstrate the power of this protein editing platform to edit cellular proteins, inserting epitope peptides, protein-specific sequences, and non-canonical amino acids (ncAAs). Importantly, we employ an endogenous tagging approach to apply our protein editing technology to endogenous proteins with minimal perturbation. We anticipate that the protein editing technology presented here will be applied to a diverse set of problems, enabling novel experiments in live mammalian cells and therefore provide unique biological insights. Subsequently, I will describe our induced proximity approaches to edit protein post-translational modifications. By combining Scalable POoled Targeting with a LIgandable Tag at Endogenous Sites (SPOTLITES) for the high-throughput tagging of endogenous proteins, with generic small molecule-based protein recruitment systems, we can screen for novel proximity-based effectors. We apply this methodology to both targeted protein degradation and targeted protein acylation. Our screens revealed a multitude of potential new effector proteins for degradation and converged on members of the CTLH complex which we demonstrate potently induce degradation. Altogether, we introduce a platform for pooled induction of endogenous protein-protein interactions that can be used to expand our toolset of effector proteins for targeted protein degradation and other forms of induced proximity.