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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 Develo...
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  
Synthetic signaling pathways
키워드  
Two-component systems
키워드  
Cell functions
키워드  
Response regulator
기타저자  
University of California, Davis Genetics
기본자료저록  
Dissertations Abstracts International. 86-04B.
전자적 위치 및 접속  
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■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.

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