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3D_Tryps SIGNED

The role of three-dimensional genome architecture in antigenic variation

Total Cost €

EC-Contrib. €

Partnership

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3D_Tryps project word cloud

Explore the words cloud of the 3D_Tryps project. It provides you a very rough idea of what is the project "3D_Tryps" about.

crispr spatial model cas9 new employed survival immune nucleus impacts plays antigens parasite causal divergent hi switching strategy regulation evolutionarily unprecedented inside variation hierarchical mechanisms links genome genomic organisms trypanosoma mutually throughput experiments host first antigenic techniques medical opened periodic evade regulator eukaryotes expression infection revealed nonrandom bridge frequency functional brucei pathogens architecture view outlined antigen despite gene translocation editing protozoan course dna organization organism sequence assays 3d relying critical systematically sequencing decades me nucleotide loci intervention probe systematic perform pathogen exclusive influence

Project "3D_Tryps" data sheet

The following table provides information about the project.

Coordinator	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 website: www.uni-muenchen.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Germany [DE]
Total cost	1˙498˙175 €
EC max contribution	1˙498˙175 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-STG
Funding Scheme	ERC-STG
Starting year	2017
Duration (year-month-day)	from 2017-04-01 to 2022-03-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 website: www.uni-muenchen.de contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	DE (MUENCHEN)	coordinator	1˙498˙175.00

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Project objective

Antigenic variation is a widely employed strategy to evade the host immune response. It has similar functional requirements even in evolutionarily divergent pathogens. These include the mutually exclusive expression of antigens and the periodic, nonrandom switching in the expression of different antigens during the course of an infection. Despite decades of research the mechanisms of antigenic variation are not fully understood in any organism. The recent development of high-throughput sequencing-based assays to probe the 3D genome architecture (Hi-C) has revealed the importance of the spatial organization of DNA inside the nucleus. 3D genome architecture plays a critical role in the regulation of mutually exclusive gene expression and the frequency of translocation between different genomic loci in many eukaryotes. Thus, genome architecture may also be a key regulator of antigenic variation, yet the causal links between genome architecture and the expression of antigens have not been studied systematically. In addition, the development of CRISPR-Cas9-based approaches to perform nucleotide-specific genome editing has opened unprecedented opportunities to study the influence of DNA sequence elements on the spatial organization of DNA and how this impacts antigen expression. I have adapted both Hi-C and CRISPR-Cas9 technology to the protozoan parasite Trypanosoma brucei, one of the most important model organisms to study antigenic variation. These techniques will enable me to bridge the field of antigenic variation research with that of genome architecture. I will perform the first systematic analysis of the role of genome architecture in the mutually exclusive and hierarchical expression of antigens in any pathogen. The experiments outlined in this proposal will provide new insight, facilitating a new view of antigenic variation and may eventually help medical intervention in T. brucei and in other pathogens relying on antigenic variation for their survival.

Publications

List of publications.
year	authors and title	journal	last update
2018	Juan-JosÃ© Vasquez, Carolin Wedel, Raul O Cosentino, T Nicolai Siegel Exploiting CRISPRâ€“Cas9 technology to investigate individual histone modifications published pages: e106-e106, ISSN: 0305-1048, DOI: 10.1093/nar/gky517	Nucleic Acids Research 46/18	2019-07-18
2018	Laura S. M. MÃ¼ller, RaÃºl O. Cosentino, Konrad U. FÃ¶rstner, Julien Guizetti, Carolin Wedel, Noam Kaplan, Christian J. Janzen, Panagiota Arampatzi, JÃ¶rg Vogel, Sascha Steinbiss, Thomas D. Otto, Antoine-Emmanuel Saliba, Robert P. Sebra, T. Nicolai Siegel Genome organization and DNA accessibility control antigenic variation in trypanosomes published pages: 121-125, ISSN: 0028-0836, DOI: 10.1038/s41586-018-0619-8	Nature 563/7729	2019-07-18

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