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Understanding T-Cell Receptor Signaling Through Computational Modeling and De-novo Protein Design
Understanding T-Cell Receptor Signaling Through Computational Modeling and De-novo Protein...
Understanding T-Cell Receptor Signaling Through Computational Modeling and De-novo Protein Design

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자료유형  
 학위논문 서양
최종처리일시  
20250211151425
ISBN  
9798383282915
DDC  
610
저자명  
White, William Louis.
서명/저자  
Understanding T-Cell Receptor Signaling Through Computational Modeling and De-novo Protein Design
발행사항  
[Sl] : University of Washington, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
67 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-01, Section: B.
주기사항  
Includes supplementary digital materials.
주기사항  
Advisor: Baker, David;Kueh, Hao Yuan.
학위논문주기  
Thesis (Ph.D.)--University of Washington, 2024.
초록/해제  
요약In order to successfully defend the host from a wide range of pathogens and cancer, T-cells must be able to recognize these threats while ignoring healthy tissues. If T-cell threat recognition is not properly calibrated, pathologies such as autoimmunity or immune deficiency can arise. The mechanisms that control T-cell recognition and activation can be broadly divided into two categories: the structural mechanism by which T-cell receptors (TCRs) can bind specifically to foreign peptides presented on the major histocompatibility complex (pMHC) but not self-pMHCs, and the biochemical mechanism by which TCR binding events are translated into T-cell activation. Here, I describe two projects that are together focused on developing tools and models to better understand each of these critical aspects of T-cell function. First, I developed a de-novo designed stabilizing domain which allows MHCs to be expressed solubly in E. coli, allowing much faster and easier production of pMHC reagents for a variety of applications in the study of pMHC-TCR interactions. Second, I developed a model of early T-cell signaling steps which explains several important aspects of TCR signaling through the clustering dynamics of signaling molecules. In combination, these two projects provide important tools and insights in the study of T-cell antigen recognition and selectivity.
일반주제명  
Bioengineering
일반주제명  
Biochemistry
일반주제명  
Immunology
일반주제명  
Microbiology
일반주제명  
Cellular biology
키워드  
Cell signaling
키워드  
Clustering
키워드  
MHC
키워드  
Protein design
키워드  
Soluble MHC
키워드  
T-cell receptor
기타저자  
University of Washington Bioengineering
기본자료저록  
Dissertations Abstracts International. 86-01B.
전자적 위치 및 접속  
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■1001  ▼aWhite,  William  Louis.
■24510▼aUnderstanding  T-Cell  Receptor  Signaling  Through  Computational  Modeling  and  De-novo  Protein  Design
■260    ▼a[Sl]▼bUniversity  of  Washington▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a67  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-01,  Section:  B.
■500    ▼aIncludes  supplementary  digital  materials.
■500    ▼aAdvisor:  Baker,  David;Kueh,  Hao  Yuan.
■5021  ▼aThesis  (Ph.D.)--University  of  Washington,  2024.
■520    ▼aIn  order  to  successfully  defend  the  host  from  a  wide  range  of  pathogens  and  cancer,  T-cells  must  be  able  to  recognize  these  threats  while  ignoring  healthy  tissues.  If  T-cell  threat  recognition  is  not  properly  calibrated,  pathologies  such  as  autoimmunity  or  immune  deficiency  can  arise.  The  mechanisms  that  control  T-cell  recognition  and  activation  can  be  broadly  divided  into  two  categories:  the  structural  mechanism  by  which  T-cell  receptors  (TCRs)  can  bind  specifically  to  foreign  peptides  presented  on  the  major  histocompatibility  complex  (pMHC)  but  not  self-pMHCs,  and  the  biochemical  mechanism  by  which  TCR  binding  events  are  translated  into  T-cell  activation.  Here,  I  describe  two  projects  that  are  together  focused  on  developing  tools  and  models  to  better  understand  each  of  these  critical  aspects  of  T-cell  function.  First,  I  developed  a  de-novo  designed  stabilizing  domain  which  allows  MHCs  to  be  expressed  solubly  in  E.  coli,  allowing  much  faster  and  easier  production  of  pMHC  reagents  for  a  variety  of  applications  in  the  study  of  pMHC-TCR  interactions.  Second,  I  developed  a  model  of  early  T-cell  signaling  steps  which  explains  several  important  aspects  of  TCR  signaling  through  the  clustering  dynamics  of  signaling  molecules.  In  combination,  these  two  projects  provide  important  tools  and  insights  in  the  study  of  T-cell  antigen  recognition  and  selectivity.
■590    ▼aSchool  code:  0250.
■650  4▼aBioengineering
■650  4▼aBiochemistry
■650  4▼aImmunology
■650  4▼aMicrobiology
■650  4▼aCellular  biology
■653    ▼aCell  signaling
■653    ▼aClustering
■653    ▼aMHC
■653    ▼aProtein  design
■653    ▼aSoluble  MHC
■653    ▼aT-cell  receptor
■690    ▼a0202
■690    ▼a0487
■690    ▼a0982
■690    ▼a0379
■690    ▼a0410
■71020▼aUniversity  of  Washington▼bBioengineering.
■7730  ▼tDissertations  Abstracts  International▼g86-01B.
■790    ▼a0250
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161648▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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