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Uncovering Transkingdom Connectivity Through Mapping Host-Microbiota Interactions
Uncovering Transkingdom Connectivity Through Mapping Host-Microbiota Interactions
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151015
- ISBN
- 9798383566329
- DDC
- 576
- 서명/저자
- Uncovering Transkingdom Connectivity Through Mapping Host-Microbiota Interactions
- 발행사항
- [Sl] : Yale University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 133 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-02, Section: B.
- 주기사항
- Advisor: Palm, Noah Walcott.
- 학위논문주기
- Thesis (Ph.D.)--Yale University, 2024.
- 초록/해제
- 요약Our microbiota, the trillions of microbes that constitutively colonize every outward-facing surface of our bodies, have diverse impacts on human physiology, yet the molecular bases for these effects remain mostly unknown. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the 'exoproteome'). Commensal microbes may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct microbiota-exoproteome interactions remain largely unexplored. We developed and validated a novel technology, BActerial Selection to Elucidate Host-microbe Interactions in high Throughput (BASEHIT), that enables proteome-scale assessment of human exoproteome-microbiome interactions. Using BASEHIT, we interrogated 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The resulting interactome revealed an extensive network of transkingdom connectivity consisting of thousands of previously undescribed host-microbe interactions involving 383 strains and 651 host proteins. Specific binding patterns within this network implied underlying biological logic: for example, conspecific strains exhibited shared exoprotein-binding patterns, and individual tissue isolates uniquely bound tissue-specific exoproteins. Furthermore, we observed dozens of unique and often strain-specific interactions with potential roles in niche colonization, tissue remodeling, and immunomodulation, and found that strains with differing host interaction profiles had divergent interactions with host cells in vitro and impacts on the host immune system in vivo. Overall, these studies expose a previously unexplored landscape of molecular-level host-microbiota interactions that may underlie causal impacts of indigenous microbes on human health and disease.
- 일반주제명
- Microbiology
- 일반주제명
- Immunology
- 일반주제명
- Cellular biology
- 일반주제명
- Health sciences
- 키워드
- Exoproteins
- 키워드
- Microbiomes
- 키워드
- Yeast display
- 기타저자
- Yale University Microbiology
- 기본자료저록
- Dissertations Abstracts International. 86-02B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008250123s2024 us c eng d■001000017160416
■00520250211151015
■006m o d
■007cr#unu||||||||
■020 ▼a9798383566329
■035 ▼a(MiAaPQ)AAI30995835
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a576
■1001 ▼aSonnert, Nicole Dak-Mei Lam.
■24510▼aUncovering Transkingdom Connectivity Through Mapping Host-Microbiota Interactions
■260 ▼a[Sl]▼bYale University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a133 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-02, Section: B.
■500 ▼aAdvisor: Palm, Noah Walcott.
■5021 ▼aThesis (Ph.D.)--Yale University, 2024.
■520 ▼aOur microbiota, the trillions of microbes that constitutively colonize every outward-facing surface of our bodies, have diverse impacts on human physiology, yet the molecular bases for these effects remain mostly unknown. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the 'exoproteome'). Commensal microbes may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct microbiota-exoproteome interactions remain largely unexplored. We developed and validated a novel technology, BActerial Selection to Elucidate Host-microbe Interactions in high Throughput (BASEHIT), that enables proteome-scale assessment of human exoproteome-microbiome interactions. Using BASEHIT, we interrogated 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The resulting interactome revealed an extensive network of transkingdom connectivity consisting of thousands of previously undescribed host-microbe interactions involving 383 strains and 651 host proteins. Specific binding patterns within this network implied underlying biological logic: for example, conspecific strains exhibited shared exoprotein-binding patterns, and individual tissue isolates uniquely bound tissue-specific exoproteins. Furthermore, we observed dozens of unique and often strain-specific interactions with potential roles in niche colonization, tissue remodeling, and immunomodulation, and found that strains with differing host interaction profiles had divergent interactions with host cells in vitro and impacts on the host immune system in vivo. Overall, these studies expose a previously unexplored landscape of molecular-level host-microbiota interactions that may underlie causal impacts of indigenous microbes on human health and disease.
■590 ▼aSchool code: 0265.
■650 4▼aMicrobiology
■650 4▼aImmunology
■650 4▼aCellular biology
■650 4▼aHealth sciences
■653 ▼aExoproteins
■653 ▼aHost-microbiota interactions
■653 ▼aMicrobiomes
■653 ▼aYeast display
■653 ▼aImmune modulation
■690 ▼a0410
■690 ▼a0982
■690 ▼a0379
■690 ▼a0566
■71020▼aYale University▼bMicrobiology.
■7730 ▼tDissertations Abstracts International▼g86-02B.
■790 ▼a0265
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160416▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
