Apparatus for the processing of single molecules

The invention relates to an apparatus(100) and a method for the processing of single molecules, particularly for the sensing or sequencing of single-stranded DNA. A bottom layer(110) and an electrically conductive top layer(120) with a first and a second slit(111,121), respectively, are disposed on top of each other such that an aperture(A) is formed by the slits. The slits(111,121) are preferably perpendicular to each other. An electrical circuit(140) may be connected to the top layer(120), allowing to sense single molecules that pass through the aperture(A)

An Epigenetics-Inspired DNA-Based Data Storage System.

Biopolymers are an attractive alternative to store and circulate information. DNA, for example, combines remarkable longevity with high data storage densities and has been demonstrated as a means for preserving digital information. Inspired by the dynamic, biological regulation of (epi)genetic information, we herein present how binary data can undergo controlled changes when encoded in synthetic DNA strands. By exploiting differential kinetics of hydrolytic deamination reactions of cytosine and its naturally occurring derivatives, we demonstrate how multiple layers of information can be stored in a single DNA template. Moreover, we show that controlled redox reactions allow for interconversion of these DNA-encoded layers of information. Overall, such interlacing of multiple messages on synthetic DNA libraries showcases the potential of chemical reactions to manipulate digital information on (bio)polymers.C.M. is grateful for the financial support by the Swiss National Science Foundation (grant number P2EZP2_152216). G.R.M. was supported by funding from Trinity College, Cambridge, the Herchel Smith fund and the Wellcome Trust. P.M. was funded by the Wellcome Trust and is currently supported by an ERC Advanced grant. P.V.D was funded by the Wellcome Trust and a Marie Curie Fellow of the European Union (grant number FP7-PEOPLE-2013-IEF/624885). The S.B. lab is supported by a program grant and core funding from Cancer Research UK (C9681/A18618), an ERC Advanced grant (339778) and by a Senior Investigator Award of the Wellcome Trust (099232/Z/12/Z). We thank Eun-Ang Raiber and Dario Beraldi for stimulating discussions and proofreading the manuscript.This is the final version of the article. It first appeared from Wiley at http://dx.doi.org/10.1002/anie.201605531

Manufacturing method of an apparatus for the processing of single molecules

The invention relates to a method for manufacturing an apparatus for the processing of single molecules. According to this method, a self-assembling resist (155) is deposited on a processing layer (110, PL) and allowed to self-assemble into a pattern of two phases (155a, 155b). One of these phases (155a) is then selectively removed, and at least one aperture is generated in the processing layer (110, PL) through the mask of the remaining resist (155b). Thus apertures of small size can readily be produced that allow for the processing of single molecules (M), for example in DNA sequencing

Genome-wide mapping of 5-hydroxymethyluracil in the eukaryote parasite Leishmania.

BACKGROUND: 5-Hydroxymethyluracil (5hmU) is a thymine base modification found in the genomes of a diverse range of organisms. To explore the functional importance of 5hmU, we develop a method for the genome-wide mapping of 5hmU-modified loci based on a chemical tagging strategy for the hydroxymethyl group. RESULTS: We apply the method to generate genome-wide maps of 5hmU in the parasitic protozoan Leishmania sp. In this genus, another thymine modification, 5-(β-glucopyranosyl) hydroxymethyluracil (base J), plays a key role during transcription. To elucidate the relationship between 5hmU and base J, we also map base J loci by introducing a chemical tagging strategy for the glucopyranoside residue. Observed 5hmU peaks are highly consistent among technical replicates, confirming the robustness of the method. 5hmU is enriched in strand switch regions, telomeric regions, and intergenic regions. Over 90% of 5hmU-enriched loci overlapped with base J-enriched loci, which occurs mostly within strand switch regions. We also identify loci comprising 5hmU but not base J, which are enriched with motifs consisting of a stretch of thymine bases. CONCLUSIONS: By chemically detecting 5hmU we present a method to provide a genome-wide map of this modification, which will help address the emerging interest in the role of 5hmU. This method will also be applicable to other organisms bearing 5hmU.FK is supported by the Wellcome Trust, DB is supported by the Herchel Smith Fund, REH is supported by the University of Cambridge and the Herchel Smith Fund, GRM was supported by Trinity College and the Herchel Smith fund, PVD is supported by Marie Curie fellowship and the Wellcome Trust. The Balasubramanian group is core-funded by a Wellcome Trust Senior Investigator Award (099232/Z/12/Z) and Cancer Research UK(C14303/A17197)