High Throughput Peptide Interaction Discovery, Epitope Mapping and “Split” proximity labelling

• Applicant: Peter Bellotti
• Subject Area: Biochemistry ; Biological and Biomimetic Chemistry ; Organic Molecular Chemistry - Synthesis and Characterisation ; Pharmacology
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516215326

The interaction between functional biomolecules, a largely unmapped macrocosm, underlies the astonishing variety and dynamism of higher forms of life. Despite the profound understanding of genotype, a large fraction of biomolecules, for instance long non-coding RNA from «pervasive transcription», has no known function. We sought to study the role of short peptides, in particular the cleavage products of signal peptides, which represent an uncharted cohort of potential cellular modulators. Combining our in-house developed photoproximity labelling technology and four-dimensional ion mobility mass spectroscopy, we aim at developing a high-throughput native peptide receptor discovery workflow. Furthermore, the development of ion mobility-m/z modifying tags will empower the spatially precise epitope microenvironment mapping.One proscriptive challenge faced by interactome studies is that countless proteins belong to multiple functional complexes with overlapping protein compositions. We aim at developing a Split-ID photochemical approach based on the Förster resonance energy-transfer to enable the study of ER/mitochondrial junctions. This approach potentially offers orders of magnitude higher spatiotemporal resolution vs state-of-the-art techniques and the gated nature of the technology adds an additional dimension to photo-proximity methodologies. Close collaboration between research groups at Weill Cornell Medicine will enable immediate assessment of the translational potential of the newly developed technologies.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Jacob B. Geri