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Characterisation and Engineering of Prokaryotic Innate and Adaptive Immune Systems
Characterisation and Engineering of Prokaryotic Innate and Adaptive Immune Systems
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152649
- ISBN
- 9798384077862
- DDC
- 610
- 서명/저자
- Characterisation and Engineering of Prokaryotic Innate and Adaptive Immune Systems
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 251 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Includes supplementary digital materials.
- 주기사항
- Advisor: Shipman, Seth.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약For the past 3.7 billion years, Earth has been the setting of perhaps the grandest and still ongoing genomic, evolutionary and ecological experiment: the war between bacteria and their viral parasites. Given the unfathomably large global viral and bacterial reservoirs, the former outnumbering the latter at a ratio of 10:1, it is estimated that viral transductions happen in the order of 2 x 1016 times per second. A sizeable fraction of these infections leads to prokaryotic death, and the subsequent estimated daily turnover of 15% of Earth's biomass. However, bacteria have not stood around idly: they have developed weapons of their own to fend against their viral invaders, in the form of immune systems.Over the course of evolutionary history, bacteria have developed multiple lines of defence to fend off infections, in the form of innate and adaptive immune systems. These immune systems, in turn, have been domesticated by researchers to develop novel biotechnological tools. Chapters 2 and 3 of this dissertation detail the repurposing of one of these innate immune systems, the bacterial retron, for precise genome editing in human cells, and its further engineering to enable multiple precise edits on individual genomes across the tree of life. Chapter 4 presents a study of the only known bacterial adaptive immune system, the CRISPR-Cas defence system. There, I attempt to discover novel host factors required for CRISPR adaptation, the process by which bacteria create immune memories of infection, and characterise SspA as a novel transcriptional regulator of the process.Taken together, this dissertation contends that bacterial immune systems are inseparable and cannot be properly understood in isolation of their cellular contexts, and argues for a more systems-biological understanding of their regulation and embeddedness within broader cell metabolism.
- 일반주제명
- Bioengineering
- 일반주제명
- Microbiology
- 일반주제명
- Genetics
- 일반주제명
- Immunology
- 키워드
- Bacteriophages
- 키워드
- Immune systems
- 키워드
- Genome editing
- 키워드
- Retron
- 기타저자
- University of California, San Francisco Bioengineering
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211152649
■006m o d
■007cr#unu||||||||
■020 ▼a9798384077862
■035 ▼a(MiAaPQ)AAI31486446
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a610
■1001 ▼aLopez, Santiago Caetano.▼0(orcid)0000-0001-7576-2438
■24510▼aCharacterisation and Engineering of Prokaryotic Innate and Adaptive Immune Systems
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a251 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aIncludes supplementary digital materials.
■500 ▼aAdvisor: Shipman, Seth.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aFor the past 3.7 billion years, Earth has been the setting of perhaps the grandest and still ongoing genomic, evolutionary and ecological experiment: the war between bacteria and their viral parasites. Given the unfathomably large global viral and bacterial reservoirs, the former outnumbering the latter at a ratio of 10:1, it is estimated that viral transductions happen in the order of 2 x 1016 times per second. A sizeable fraction of these infections leads to prokaryotic death, and the subsequent estimated daily turnover of 15% of Earth's biomass. However, bacteria have not stood around idly: they have developed weapons of their own to fend against their viral invaders, in the form of immune systems.Over the course of evolutionary history, bacteria have developed multiple lines of defence to fend off infections, in the form of innate and adaptive immune systems. These immune systems, in turn, have been domesticated by researchers to develop novel biotechnological tools. Chapters 2 and 3 of this dissertation detail the repurposing of one of these innate immune systems, the bacterial retron, for precise genome editing in human cells, and its further engineering to enable multiple precise edits on individual genomes across the tree of life. Chapter 4 presents a study of the only known bacterial adaptive immune system, the CRISPR-Cas defence system. There, I attempt to discover novel host factors required for CRISPR adaptation, the process by which bacteria create immune memories of infection, and characterise SspA as a novel transcriptional regulator of the process.Taken together, this dissertation contends that bacterial immune systems are inseparable and cannot be properly understood in isolation of their cellular contexts, and argues for a more systems-biological understanding of their regulation and embeddedness within broader cell metabolism.
■590 ▼aSchool code: 0034.
■650 4▼aBioengineering
■650 4▼aMicrobiology
■650 4▼aGenetics
■650 4▼aImmunology
■653 ▼aBacterial immunity
■653 ▼aBacteriophages
■653 ▼aImmune systems
■653 ▼aGenome editing
■653 ▼aRetron
■690 ▼a0202
■690 ▼a0410
■690 ▼a0982
■690 ▼a0369
■71020▼aUniversity of California, San Francisco▼bBioengineering.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163291▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
