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Discovery of Host-Microbiota Interac...

Rosen, Connor Edwin.

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Discovery of Host-Microbiota Interactions.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Discovery of Host-Microbiota Interactions./
Author:	Rosen, Connor Edwin.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	202 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
Contained By:	Dissertations Abstracts International83-02B.
Subject:	Immunology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28321441
ISBN:	9798534651829

Discovery of Host-Microbiota Interactions.
Rosen, Connor Edwin.

Discovery of Host-Microbiota Interactions. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 202 p.

Source: Dissertations Abstracts International, Volume: 83-02, Section: B.

Thesis (Ph.D.)--Yale University, 2021.

This item must not be sold to any third party vendors.

The microbiota, comprising the trillions of microorganisms that colonize barrier tissues, exert profound effects on host health and disease. Microbial effects on host physiology have been illuminated by a wealth of sequencing-based approaches that enumerate bacterial species, strains, genes, and products (collectively, "multi-omics" approaches) at different tissue sites and in different human populations. Microbes may influence local physiology at their site of residence, as well as having systemic effects including perturbation of organism-wide metabolism, with wide-ranging consequences. The molecular mechanisms by which microbes mediate both local and systemic effects, however, remain mostly unclear. This is in part due to technological limitations in profiling microbes at the scales necessary to characterize the thousands of unique strains and species that comprise the collective human microbiota. The identification of specific host pathways engaged or modulated by particular microbes will provide insight into how the microbiota impacts host physiology, and suggest nodes of intervention for the amelioration of microbiota-mediated disorders. In this thesis, I will describe a new technological approach to profile direct microbial interactions with the host and how discoveries enabled by this technique may shape our future understanding of host-microbe interactions.In Chapter 1, I present a brief introduction to the microbiota, with a particular focus of the intestinal microbiota, along with an introduction to the importance of "functional profiling" to describe and classify the microbiota. The intestine is the most densely populated organ by microbial cells, and includes a diverse range of microenvironments that support a large diversity of microbes. Functional profiling may support traditional multi-omics approaches to identify critical microbes or pathways in host-microbe connection. In Chapter 2, I discuss selective pressures facing the intestinal microbiota, to contextualize the functional profiling program of interest, an effort to discovery direct cellular host-microbe interactions. In Chapter 3, I introduce yeast surface display methodology and the design and creation of a library of human exoproteins that is useful for interrogating binding partners of host exoproteins, validated and highlighted by the discovery of the targets of human autoantibodies in autoimmune diseases. In Chapter 4, I present BASEHIT, a new technique for screening microbial cells using yeast surface display libraries. I use BASEHIT to characterize the host binding patterns of hundreds of microbes and describe the nature of interactions discovered as well as several particular interactions of interest. In Chapters 5, I illustrate how BASEHIT may be applied to study mechanisms of bacterial pathogenesis, through the lens of the causative agent of Lyme disease, Borrelia burgdorferi.

ISBN: 9798534651829Subjects--Topical Terms:

611031
Immunology.
Subjects--Index Terms:

Host-microbiota interactions

Discovery of Host-Microbiota Interactions.
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500 $a Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
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520 $a The microbiota, comprising the trillions of microorganisms that colonize barrier tissues, exert profound effects on host health and disease. Microbial effects on host physiology have been illuminated by a wealth of sequencing-based approaches that enumerate bacterial species, strains, genes, and products (collectively, "multi-omics" approaches) at different tissue sites and in different human populations. Microbes may influence local physiology at their site of residence, as well as having systemic effects including perturbation of organism-wide metabolism, with wide-ranging consequences. The molecular mechanisms by which microbes mediate both local and systemic effects, however, remain mostly unclear. This is in part due to technological limitations in profiling microbes at the scales necessary to characterize the thousands of unique strains and species that comprise the collective human microbiota. The identification of specific host pathways engaged or modulated by particular microbes will provide insight into how the microbiota impacts host physiology, and suggest nodes of intervention for the amelioration of microbiota-mediated disorders. In this thesis, I will describe a new technological approach to profile direct microbial interactions with the host and how discoveries enabled by this technique may shape our future understanding of host-microbe interactions.In Chapter 1, I present a brief introduction to the microbiota, with a particular focus of the intestinal microbiota, along with an introduction to the importance of "functional profiling" to describe and classify the microbiota. The intestine is the most densely populated organ by microbial cells, and includes a diverse range of microenvironments that support a large diversity of microbes. Functional profiling may support traditional multi-omics approaches to identify critical microbes or pathways in host-microbe connection. In Chapter 2, I discuss selective pressures facing the intestinal microbiota, to contextualize the functional profiling program of interest, an effort to discovery direct cellular host-microbe interactions. In Chapter 3, I introduce yeast surface display methodology and the design and creation of a library of human exoproteins that is useful for interrogating binding partners of host exoproteins, validated and highlighted by the discovery of the targets of human autoantibodies in autoimmune diseases. In Chapter 4, I present BASEHIT, a new technique for screening microbial cells using yeast surface display libraries. I use BASEHIT to characterize the host binding patterns of hundreds of microbes and describe the nature of interactions discovered as well as several particular interactions of interest. In Chapters 5, I illustrate how BASEHIT may be applied to study mechanisms of bacterial pathogenesis, through the lens of the causative agent of Lyme disease, Borrelia burgdorferi.
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650 4 $a Molecular biology. $3 517296
650 4 $a Physiology. $3 518431
650 4 $a Peer review. $3 624199
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