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Exploring the Epigenome by Multiplexed Physical Mapping of Individual Chromosomes

Project description

Exploring the effect of long-range epigenetic modifications

Epigenetic modifications are chemical tags on DNA and chromatin that affect DNA accessibility and gene expression. They are heritable but do not involve alterations in the actual DNA sequence. Scientists of the EU-funded MultiplexGenomics project are interested to discover how epigenetic modification located far away from a gene can influence expression and can predispose individuals to certain types of cancer. Researchers will develop a platform for genomic profiling and perform physical and chemical mapping of individual chromosomes. The project has the potential to unveil novel control networks and hidden long-range regulation of genomic locations, advancing genomics science.

Objective

The genome is composed of the genetic code and a rich repertoire of epigenetic chemical DNA modifications, the Epigenome, with distinct signatures in health and disease. Unmasking the interplay between different genomic features is critical for understanding the operating system of life. Specifically, revealing long-range epigenetic regulation may uncover predisposition to cancer. Nevertheless, due to the short read-length of single-cell next-generation sequencing, there is no method today that can integrate multiple genomic observables, on the same genome and at the same time. The missing picture constitutes a major genomic “blind spot”, obscuring epigenetic regulation of gene expression. This project aims to provide a multiplexed view of the genome never before accessible. I will utilize single-molecule physical and chemical mapping of individual chromosomes to discover long-range epigenetic correlations, focusing on markers for predisposition to breast cancer. I will approach multiplexing by applying optical and electrical sensing concepts to detect chemical tags attached to long genomic DNA molecules. Equipped with a toolbox of biochemical DNA labeling reactions, I will develop a unique spectral imager for simultaneous acquisition of high-content genomic information from DNA stretched in nanochannel arrays. DNA tagging will also be used to enhance electrical contrast for nanopore epigenetic sequencing. Finally, by combining electric sensing inside nanochannels I will develop new integrated devices for electro-optical genomic analysis. Together, these developments cover the full range of genomic length scales and resolution. MultiplexGenomics will establish a groundbreaking experimental framework for genetic/epigenetic profiling of native chromosomal DNA. A successful completion of this project will make possible the discovery of novel control networks and hidden long-range regulation, opening new horizons for basic genomic research and personalized medicine.

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Coordinator

TEL AVIV UNIVERSITY
Net EU contribution
€ 2 750 000,00
Other funding
€ 0,00

Beneficiaries (1)