Dataset Information

Microbiotal-Host Interactions and Hypertension.

ABSTRACT: Hypertension, or elevated blood pressure (BP), has been extensively researched over decades and clearly demonstrated to be caused due to a combination of host genetic and environmental factors. Although much research remains to be conducted to pin-point the precise genetic elements on the host genome that control BP, new lines of evidence are emerging to indicate that, besides the host genome, the genomes of all indigenous commensal micro-organisms, collectively referred to as the microbial metagenome or microbiome, are important, but largely understudied, determinants of BP. Unlike the rigid host genome, the microbiome or the "second genome" can be altered by diet or microbiotal transplantation in the host. This possibility is attractive from the perspective of exploiting the microbiotal composition for clinical management of inherited hypertension. Thus, focusing on the limited current literature supporting a role for the microbiome in BP regulation, this review highlights the need to further explore the role of the co-existence of host and the microbiota as an organized biological unit called the "holobiont" in the context of BP regulation.

SUBMITTER: Galla S

PROVIDER: S-EPMC6347099 | biostudies-other | 2017 May

REPOSITORIES: biostudies-other

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Microbiotal-Host Interactions and Hypertension.

Galla Sarah S Chakraborty Saroj S Mell Blair B Vijay-Kumar Matam M Joe Bina B

Physiology (Bethesda, Md.) 20170501 3

Hypertension, or elevated blood pressure (BP), has been extensively researched over decades and clearly demonstrated to be caused due to a combination of host genetic and environmental factors. Although much research remains to be conducted to pin-point the precise genetic elements on the host genome that control BP, new lines of evidence are emerging to indicate that, besides the host genome, the genomes of all indigenous commensal micro-organisms, collectively referred to as the microbial meta ...[more]

PMID: 28404738

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Project description:The goal of this project is to understand the etiology and pathology of host-pathogen interaction using high-throughput cellular phenotyping. By combining the expertise in pathogen biology, informatics and stem cell biology across the institute, this project will use targeted genetic modification in mouse embryonic stem cells to identify functions of host genes in innate immunity. We will also explore the biology of mouse embryonic stem cells and their differentiation into immune competent cells. To this end we will generate homozygous and inducible knockout lines in mouse embryonic stem cells, which will be differentiated into immune competent cells, such as macrophages or dendritic cells. These will be subjected to a panel of immune challenge and stimulation assays to characterise the functions of the disrupted genes. To identify new functions for mammalian genes in innate immunity we will:\Generate a panel of homozygous inducible gene knockout mouse ES cell lines working from a list of ca. 80 candidate genes (MGP phenotyping and GWAS hits). \Scale up differentiation protocols for immune challenge and stimulation assays.\Benchmark in vitro differentiated ES cell models against primary immune cells from selected MGP mouse lines and eventually against human iPS cells.\Screen a panel of 30 genetically modified cell lines in immunological challenge and stimulation assays, defining phenotypes at the cellular level by high content imaging, biochemically by assaying cytokine production, and at the molecular level by transcriptome analysis.\Define novel gene functions in innate immunity through network analysis of gene expression data from all challenged cell lines.\In the longer term scale up the production and phenotyping of genetically modified cell lines (mouse or human as appropriate).This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

Dataset Information

Microbiotal-Host Interactions and Hypertension.

Publications

Microbiotal-Host Interactions and Hypertension.

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