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Beads on String Genomics: Experimental Toolbox for Unmasking Genetic / Epigenetic Variation in Genomic DNA and Chromatin

Objective

Next generation sequencing (NGS) is revolutionizing all fields of biological research but it fails to extract the full range of information associated with genetic material and is lacking in its ability to resolve variations between genomes. The high degree of genome variation exhibited both on the population level as well as between genetically “identical” cells (even in the same organ) makes genetic and epigenetic analysis on the single cell and single genome level a necessity.
Chromosomes may be conceptually represented as a linear one-dimensional barcode. However, in contrast to a traditional binary barcode approach that considers only two possible bits of information (1 & 0), I will use colour and molecular structure to expand the variety of information represented in the barcode. Like colourful beads threaded on a string, where each bead represents a distinct type of observable, I will label each type of genomic information with a different chemical moiety thus expanding the repertoire of information that can be simultaneously measured. A major effort in this proposal is invested in the development of unique chemistries to enable this labelling.
I specifically address three types of genomic variation: Variations in genomic layout (including DNA repeats, structural and copy number variations), variations in the patterns of chemical DNA modifications (such as methylation of cytosine bases) and variations in the chromatin composition (including nucleosome and transcription factor distributions). I will use physical extension of long DNA molecules on surfaces and in nanofluidic channels to reveal this information visually in the form of a linear, fluorescent “barcode” that is read-out by advanced imaging techniques. Similarly, DNA molecules will be threaded through a nanopore where the sequential position of “bulky” molecular groups attached to the DNA may be inferred from temporal modulation of an ionic current measured across the pore.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/chromosome
  • /natural sciences/biological sciences/genetics and heredity/genome

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

TEL AVIV UNIVERSITY
Address
Ramat Aviv
69978 Tel Aviv
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 627 600
Principal investigator
Yuval Ebenstein (Dr.)
Administrative Contact
Lea Pais (Ms.)

Beneficiaries (1)

TEL AVIV UNIVERSITY
Israel
EU contribution
€ 1 627 600
Address
Ramat Aviv
69978 Tel Aviv
Activity type
Higher or Secondary Education Establishments
Principal investigator
Yuval Ebenstein (Dr.)
Administrative Contact
Lea Pais (Ms.)