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Reading through proteins with graphene: NWO Vidi grant awarded to Dr. Grégory Schneider

While there are numerous and extremely advanced methods to sequence the genome, only a few methods exist to sequence the proteome. The Vidi project of Grégory Schneider promises to shed light on the most difficult paradigm of proteomics: achieving an error-free determination of the sequence of single protein molecules in real time.

Protein sequencing is hampered by three major roadblocks: i) proteins cannot be amplified as it is for DNA, ii) proteins have to be fragmented, and iii) unlike for DNA, 20 fluorescent amino acid tags without spectrum overlap simply does not exist.

Grégory Schneider proposes to develop a new single molecule technique inspired from nanopores (widely used to study DNA), that can read the sequence of an individual protein from head-to- tail, amino acid per amino acid, molecule after molecule. To date, sensing individual amino acids in proteins has been impossible because typical single-molecule nanopore sensors devices are thick (at least as thick as a protein). Graphene – a one atom thin material – has the potential to act as a sensor, primarily the edges of graphene. To sequence proteins, graphene will be sculpted into a nanogap (i.e., two layers of graphene separated by a physical gap on the order of the size of a protein molecule), through which unfolded proteins will be driven from head to tail under an electric field. As the protein translocates, the nanogap will be probed electrically and the amino acid sequence will be determined from the electrical readout of the graphene nanogap.

Dr. Schneider believes that this project has the potential to lead to groundbreaking changes in complete proteome mapping which will bring enormous benefits to the healthcare sector. Indeed, the early stage identification of a disease-specific marker can greatly improve the clinical success rate and reduce mortality, notably in protein-prone diseases such as neurodegenerative and protein-aggregation diseases.

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