Single molecule protein sequencing using biological nanopores
Despite the importance of post-translational variation to the function of proteins in a living organism, sequencing proteins to study these variations is still a costly and time-consuming process, with intrinsic limitations. Prote...
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Información proyecto SMPSBN
Duración del proyecto: 23 meses
Fecha Inicio: 2020-04-01
Fecha Fin: 2022-03-31
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Despite the importance of post-translational variation to the function of proteins in a living organism, sequencing proteins to study these variations is still a costly and time-consuming process, with intrinsic limitations. Protein sequencing and detection of post-translational modifications (PTMs) by mass spectrometry, the current gold standard, requires extensive sample preparation and large sample sizes, and possesses a limited dynamic range with respect to sample concentration. These limitations severely restrict its application to biological and clinical problems. A robust method for sequencing proteins and detecting PTMs at the single-molecule level would be revolutionary for proteomics research, allowing biologists to quantify low-abundance proteins as well as distributions and correlations of PTM patterns, all at a single-cell level. I propose a first-of-kind method for protein sequencing with applications in fundamental biology, cancer immunotherapy, and pharmaceutical development. This method uses biological nanopores in a manner similar to nanopore DNA sequencing, an established single-molecule sequencing technology capable of high throughput and single-molecule sensitivity. Developing this method for protein sequencing comes with many significant challenges, which will be addressed over the course of the proposed research.