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Improving the molecular to digital interface for <fast, scalable, accessible, secure> molecular information systems
Improving the molecular-to-digital interface for fast, scalable, accessible, and secure molecular information systems is central to our research. Integration of silicon and biomolecular systems offers transformative potential, enabling hybrid computing systems that merge molecular data storage and processing with electronics. This vision includes generalizable platforms for the integration of electronics and biological systems. While biomolecular computers may not match semiconductor speeds, biological components offer distinct advantages: they are smaller, more energy-efficient, massively parallel, and can directly interface with natural biological systems for 'near-data' processing. These features enable biological devices to operate in environments where traditional hardware falls short, such as within the human body, and to achieve computational power for data-intensive tasks.
Our work addresses the key challenges in this space—developing scalable mechanisms for accessing molecular data, enhancing communication between electronic and biological components, and improving the design and fabrication of these systems at scale. Nanopore-based protein sequencing plays a pivotal role in these efforts, offering a unique ability to decode individual proteins and understand their roles in biological systems at a granular level. Beyond biological understanding, nanopore technologies enable proteins to potentially serve as molecular recorders and data storage units, creating new possibilities for information storage, biological monitoring, and real-time tracking of molecular events. This dual capability of nanopore protein sequencing positions it as a foundational technology for the future of molecular information systems and biological research.
Improving the molecular-to-digital interface for fast, scalable, accessible, and secure molecular information systems is central to our research. Integration of silicon and biomolecular systems offers transformative potential, enabling hybrid computing systems that merge molecular data storage and processing with electronics. This vision includes generalizable platforms for the integration of electronics and biological systems. While biomolecular computers may not match semiconductor speeds, biological components offer distinct advantages: they are smaller, more energy-efficient, massively parallel, and can directly interface with natural biological systems for 'near-data' processing. These features enable biological devices to operate in environments where traditional hardware falls short, such as within the human body, and to achieve computational power for data-intensive tasks.
Our work addresses the key challenges in this space—developing scalable mechanisms for accessing molecular data, enhancing communication between electronic and biological components, and improving the design and fabrication of these systems at scale. Nanopore-based protein sequencing plays a pivotal role in these efforts, offering a unique ability to decode individual proteins and understand their roles in biological systems at a granular level. Beyond biological understanding, nanopore technologies enable proteins to potentially serve as molecular recorders and data storage units, creating new possibilities for information storage, biological monitoring, and real-time tracking of molecular events. This dual capability of nanopore protein sequencing positions it as a foundational technology for the future of molecular information systems and biological research.
Nanopore Proteomics: towards single-molecule protein sequencing and PTM detection
While genomic analysis illuminates the blueprints used by organisms to store and propagate information, proteins are the principal active ingredients in the recipe of life. Thus, our ability to understand and engineer complex biological processes hinges on elucidating the structure and function of whole proteomes -- robust technologies to identify and characterize proteins are vital to this effort. Towards this goal, a primary focus of our research is developing new methods of protein analysis. Currently, we're advancing nanopore sensing technology for interrogation of intact protein strands and peptide fragments. This process results in a series of ionic current blockade data that, when combined with machine learning, can be diagnostic of protein/peptide structure at the single-molecule level. This work represents the first steps towards developing the principles of this technology as a general platform for protein and post-translational modification (PTM) identification, and is aimed at achieving the resolution required to fully grasp the complexities of the proteome.
Related pubs:
Related pubs:
- Motone K*, Kontogiorgos-Heintz D*, Wee J, Kurihara K, Yang S, Roote G, Fox O, Fang Y, Queen M, Tolhurst M, Cardozo N, Jain M, Nivala J. Multi-pass, single-molecule nanopore reading of long protein strands. Nature. 2024.
- Motone K, Nivala J. Not if but when nanopore protein sequencing meets single-cell proteomics. Nat. Methods. 20:336-338. 2023.
- Motone K, Cardozo N, Nivala J. Herding cats: label-based approaches in protein translocation though nanopore sensors for single-molecule protein sequence analysis. iScience. 2021.
- Cardozo N*, Zhang K*, Doroschak K*, Nguyen A, Siddiqui Z, Bogard N, Strauss K, Ceze L, Nivala J. Multiplexed direct detection of barcoded protein reporters on a nanopore array. Nat. Biotechnol. 2021.
- Nivala J, Marks DB, Akeson M. Unfoldase-mediated protein translocation through an α-hemolysin nanopore. Nature Biotechnol. (3):247-50. PMID: 23376966. 2013.
- Nivala J, Mulroney L, Li G, Schreiber J, Akeson M. Discrimination among protein variants using an unfoldase-coupled nanopore. ACS Nano. 23;8(12):12365-75. PMID: 25402970. 2014.