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Two-Component Systems in Human Cells: A Basic Look at LOV and Hno Pathways for Tool Development to Advance Immunotherapy
Two-Component Systems in Human Cells: A Basic Look at LOV and Hno Pathways for Tool Development to Advance Immunotherapy
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151516
- ISBN
- 9798384483526
- DDC
- 574
- 저자명
- Sernas, Diana.
- 서명/저자
- Two-Component Systems in Human Cells: A Basic Look at LOV and Hno Pathways for Tool Development to Advance Immunotherapy
- 발행사항
- [Sl] : University of California, Davis, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 55 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
- 주기사항
- Advisor: Collins, Sean R.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Davis, 2024.
- 초록/해제
- 요약Our immune system responds to extracellular cues to protect our health by coordinating necessary cell functions from cell motility to apoptosis. Engineering signaling pathways controlling these processes is rapidly becoming a powerful approach for developing new biomedical technology, with cancer immunotherapies serving as a prominent example. However, most current strategies rely on modifying or repurposing endogenous human signaling cascades. This can result in unintended crosstalk between the synthetic signaling pathways and the complex native signaling of human cells. Two-component systems (TCS) could address this challenge and establish a scientific foundation for systematically improving and adding to the natural abilities of cells to sense and respond to their environment in a robust yet flexible manner. With a newly paved avenue for engineering cell communication, researchers could develop strategic signaling cascades in any human cell for their specific research interests. Importantly, TCS are absent in human cells, but present in all three domains of life, and offer diverse yet simple and linear signaling pathways. In TCS, ligand binding modulates a histidine kinase (HK) sensor, a protein characteristically containing separate ligand binding and HK domains. When activated, the HK transfers a phosphoryl group to the response regulator (RR), and the phosphorylated RR activates a specific downstream response through mechanisms ranging from protein-to-protein interactions to transcription. In its inactive state, the HK acts as a phosphatase. These studies focus on a light-sensitive LOV TCS and a nitric oxide-sensitive Hno TCS as candidate model pathways for modifying mammalian cells. We demonstrated constitutive activity with the LOV pathway and tested several modifications to achieve light sensitivity. While some modifications affected pathway output, all tested pathways appeared to have light-independent constitutive activity.
- 일반주제명
- Biology
- 일반주제명
- Cellular biology
- 일반주제명
- Microbiology
- 일반주제명
- Immunology
- 키워드
- Cell functions
- 기타저자
- University of California, Davis Genetics
- 기본자료저록
- Dissertations Abstracts International. 86-04B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211151516
■006m o d
■007cr#unu||||||||
■020 ▼a9798384483526
■035 ▼a(MiAaPQ)AAI31300732
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aSernas, Diana.
■24510▼aTwo-Component Systems in Human Cells: A Basic Look at LOV and Hno Pathways for Tool Development to Advance Immunotherapy
■260 ▼a[Sl]▼bUniversity of California, Davis▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a55 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-04, Section: B.
■500 ▼aAdvisor: Collins, Sean R.
■5021 ▼aThesis (Ph.D.)--University of California, Davis, 2024.
■520 ▼aOur immune system responds to extracellular cues to protect our health by coordinating necessary cell functions from cell motility to apoptosis. Engineering signaling pathways controlling these processes is rapidly becoming a powerful approach for developing new biomedical technology, with cancer immunotherapies serving as a prominent example. However, most current strategies rely on modifying or repurposing endogenous human signaling cascades. This can result in unintended crosstalk between the synthetic signaling pathways and the complex native signaling of human cells. Two-component systems (TCS) could address this challenge and establish a scientific foundation for systematically improving and adding to the natural abilities of cells to sense and respond to their environment in a robust yet flexible manner. With a newly paved avenue for engineering cell communication, researchers could develop strategic signaling cascades in any human cell for their specific research interests. Importantly, TCS are absent in human cells, but present in all three domains of life, and offer diverse yet simple and linear signaling pathways. In TCS, ligand binding modulates a histidine kinase (HK) sensor, a protein characteristically containing separate ligand binding and HK domains. When activated, the HK transfers a phosphoryl group to the response regulator (RR), and the phosphorylated RR activates a specific downstream response through mechanisms ranging from protein-to-protein interactions to transcription. In its inactive state, the HK acts as a phosphatase. These studies focus on a light-sensitive LOV TCS and a nitric oxide-sensitive Hno TCS as candidate model pathways for modifying mammalian cells. We demonstrated constitutive activity with the LOV pathway and tested several modifications to achieve light sensitivity. While some modifications affected pathway output, all tested pathways appeared to have light-independent constitutive activity.
■590 ▼aSchool code: 0029.
■650 4▼aBiology
■650 4▼aCellular biology
■650 4▼aMicrobiology
■650 4▼aImmunology
■653 ▼aSynthetic signaling pathways
■653 ▼aTwo-component systems
■653 ▼aCell functions
■653 ▼aResponse regulator
■690 ▼a0306
■690 ▼a0379
■690 ▼a0410
■690 ▼a0982
■71020▼aUniversity of California, Davis▼bGenetics.
■7730 ▼tDissertations Abstracts International▼g86-04B.
■790 ▼a0029
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162034▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.


