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Enteroendocrine Regulation of Metabolism and Innate Immunity in Drosophila melanogaster.
Enteroendocrine Regulation of Metabolism and Innate Immunity in Drosophila melanogaster.
상세정보
- 자료유형
- 학위논문(국외)
- 기본표목-개인명
- 표제와 책임표시사항
- Enteroendocrine Regulation of Metabolism and Innate Immunity in Drosophila melanogaster.
- 발행, 배포, 간사 사항
- 발행, 배포, 간사 사항
- 형태사항
- 107 p.
- 일반주기
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 일반주기
- Advisor: Watnick, Paula I.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2025.
- 요약 등 주기
- 요약Despite comprising a very small percentage of the total intestinal epithelium cell population, enteroendocrine cells (EECs) collectively form the largest endocrine organ in the body, secreting over 20 peptide hormones, or enteroendocrine peptides (EEPs), that regulate several physiological processes, including feeding behavior, metabolism, and immunity. Drosophila melanogaster, also known as the common fruit fly, shares structural and functional homology with the mammalian gastrointestinal tract and has therefore served as an excellent model organism to study intestinal physiology. My thesis work explores the role and regulation of the Drosophila EEP tachykinin (Tk) in the context of innate immunity and intestinal and systemic lipid metabolism. Previous work by the lab has established that activation of innate immune signaling in EECs induces expression of Tk and subsequent production of antimicrobial peptides (AMPs). In the first part of my thesis work, I discovered that, in addition to AMPs, Tk activates expression of Peritrophin-15a, a chitin-binding protein that is part of the protective peritrophic matrix (PM) that lines the intestinal epithelium. I further found that Peritrophin-15a is necessary for robust intestinal colonization by the pathogen V. cholerae and that, in addition to Drosophila, other arthropods that associate with V. cholerae in the environment express close structural homologs of Peritrophin-15a. Our findings suggest that V. cholerae might exploit activation of the host innate immune response and upregulation of Peritrophin-15a to increase adhesion to the intestinal surface of environmental arthropod hosts. Much like mammalian EECs, Drosophila EECs express nutrient transporters and G protein-coupled receptors (GPCRs) that sense intestinal nutrient status to regulate EEP production. In the second part of my thesis work, I found that the EEC-exclusive GPCR GulpR regulates expression of Tk and other EEPs. I also report that, through Tk, GulpR modulates utilization of systemic lipid stores when flies experience starvation but not infection stress. This suggests that activation of lipid mobilization in response to nutrient limitation and infection are regulated via different mechanisms. Overall, my thesis work identifies a GPCR that regulates expression of Tk and other EEPs in Drosophila, discovers additional roles of Tk in modulating innate immunity and metabolism, and identifies a protein produced by arthropods that may contribute to the survival and persistence of the human pathogen V. cholerae in the environment.
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 부출표목-단체명
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 원문정보보기
MARC
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aBarraza, Daniela.▼0(orcid)0000-0002-6719-6197
■24510▼aEnteroendocrine Regulation of Metabolism and Innate Immunity in Drosophila melanogaster.
■260 ▼a[S.l.]▼bHarvard University. ▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a107 p.
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Watnick, Paula I.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2025.
■520 ▼aDespite comprising a very small percentage of the total intestinal epithelium cell population, enteroendocrine cells (EECs) collectively form the largest endocrine organ in the body, secreting over 20 peptide hormones, or enteroendocrine peptides (EEPs), that regulate several physiological processes, including feeding behavior, metabolism, and immunity. Drosophila melanogaster, also known as the common fruit fly, shares structural and functional homology with the mammalian gastrointestinal tract and has therefore served as an excellent model organism to study intestinal physiology. My thesis work explores the role and regulation of the Drosophila EEP tachykinin (Tk) in the context of innate immunity and intestinal and systemic lipid metabolism. Previous work by the lab has established that activation of innate immune signaling in EECs induces expression of Tk and subsequent production of antimicrobial peptides (AMPs). In the first part of my thesis work, I discovered that, in addition to AMPs, Tk activates expression of Peritrophin-15a, a chitin-binding protein that is part of the protective peritrophic matrix (PM) that lines the intestinal epithelium. I further found that Peritrophin-15a is necessary for robust intestinal colonization by the pathogen V. cholerae and that, in addition to Drosophila, other arthropods that associate with V. cholerae in the environment express close structural homologs of Peritrophin-15a. Our findings suggest that V. cholerae might exploit activation of the host innate immune response and upregulation of Peritrophin-15a to increase adhesion to the intestinal surface of environmental arthropod hosts. Much like mammalian EECs, Drosophila EECs express nutrient transporters and G protein-coupled receptors (GPCRs) that sense intestinal nutrient status to regulate EEP production. In the second part of my thesis work, I found that the EEC-exclusive GPCR GulpR regulates expression of Tk and other EEPs. I also report that, through Tk, GulpR modulates utilization of systemic lipid stores when flies experience starvation but not infection stress. This suggests that activation of lipid mobilization in response to nutrient limitation and infection are regulated via different mechanisms. Overall, my thesis work identifies a GPCR that regulates expression of Tk and other EEPs in Drosophila, discovers additional roles of Tk in modulating innate immunity and metabolism, and identifies a protein produced by arthropods that may contribute to the survival and persistence of the human pathogen V. cholerae in the environment.
■590 ▼aSchool code: 0084.
■650 4▼aMolecular biology.
■650 4▼aPublic health.
■650 4▼aBiology.
■650 4▼aBiochemistry.
■650 4▼aEndocrinology.
■653 ▼aEnteroendocrine cells
■653 ▼aGulpR modulates
■653 ▼aIntestine
■653 ▼aPeritrophin
■653 ▼aTachykinin
■653 ▼aVibrio cholerae
■690 ▼a0307
■690 ▼a0573
■690 ▼a0306
■690 ▼a0487
■690 ▼a0409
■71020▼aHarvard University▼bBiological and Biomedical Sciences.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357404▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
