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Uncovering How Bacteria Sense and Respond to Chemically Diverse Corrinoids Through Cobalamin Riboswitch Gene Regulation- [electronic resource]
Uncovering How Bacteria Sense and Respond to Chemically Diverse Corrinoids Through Cobalam...
Uncovering How Bacteria Sense and Respond to Chemically Diverse Corrinoids Through Cobalamin Riboswitch Gene Regulation- [electronic resource]

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자료유형  
 학위논문파일 국외
최종처리일시  
20240214095906
ISBN  
9798380621144
DDC  
576
저자명  
Kennedy, Kristopher J.
서명/저자  
Uncovering How Bacteria Sense and Respond to Chemically Diverse Corrinoids Through Cobalamin Riboswitch Gene Regulation - [electronic resource]
발행사항  
[S.l.]: : University of California, Berkeley., 2021
발행사항  
Ann Arbor : : ProQuest Dissertations & Theses,, 2021
형태사항  
1 online resource(102 p.)
주기사항  
Source: Dissertations Abstracts International, Volume: 85-04, Section: B.
주기사항  
Advisor: Taga, Michiko E.
학위논문주기  
Thesis (Ph.D.)--University of California, Berkeley, 2021.
사용제한주기  
This item must not be sold to any third party vendors.
초록/해제  
요약Cells actively sense and integrate information about their internal and external environments to execute adaptive physiological responses. This makes it possible to survive fluctuating and oftentimes harsh environmental conditions. Controlling the expression of genes is part of this vital cellular process. Indeed, since the birth of molecular biology theory, a multitude of cellular mechanisms have been found to control virtually every aspect of the flow of genetic information from DNA to RNA to functional proteins. The revelation that RNAs are more than just passive messengers between DNA and proteins was a turning point in the field of molecular biology. We now recognize that many types of RNA actively fold into complex three-dimensional structures to carry out important cellular functions with sophistication, precision, and efficiency that rivals proteins. A prime example are riboswitches - structured noncoding RNAs that sense specific small molecule effectors by direct binding and function as cis-regulatory genetic switches. My dissertation research focuses on the forms and functions of the cobalamin riboswitches and how they are impacted by the exceptional chemical diversity of naturally occurring variants of cobalamin known as corrinoids.I begin the first chapter with a broad overview of bacterial gene regulation with specific emphasis on mechanisms of transcriptional and translational control. This sets the stage for delving into the distinctive elements of riboswitch structure, mechanism, and function. I also describe how various riboswitch classes connect to the cellular processes which they control. Lastly, I describe in detail the cobalamin riboswitch class and the roles that corrinoids play in bacterial physiology.The second chapter describes the bulk of my endeavors as a graduate student researcher in the Taga Lab examining the corrinoid specificity of cobalamin riboswitches. The large number of bacterial metabolic pathways that involve corrinoids and the numerous types of corrinoid cofactors and intermediates present a puzzle as to how cells can effectively use cobalamin riboswitches to control their corrinoid-related physiology. The approach I took leveraged two strengths of the Taga Lab's expertise: bacterial molecular genetics and biochemical production of commercially unavailable corrinoid molecules. I engineered an in vivo fluorescence reporter system to measure the responses of several cobalamin riboswitches to several corrinoids. From the patterns of corrinoid selectivity that I observed in my experiments, I developed a mechanistic hypothesis for corrinoid specificity of cobalamin riboswitch-based gene regulation in bacteria. Furthermore, I propose a regulatory strategy that attempts to explain how corrinoid specificities of gene regulation and bacterial physiology are functionally connected.In the third chapter, I explore the functional versatility of cobalamin riboswitches. As the second most prevalent class of riboswitches, I speculated that novel functional variations should arise from the diversity of cobalamin riboswitch sequences. To increase the likelihood of finding uncommon functional variants, I focused on atypical cobalamin riboswitch regulon architectures among bacterial species that specialize in corrinoid metabolism. This rationale enabled me to successfully identify a novel activator cobalamin riboswitch, dissect modular functionalities of tandemly linked cobalamin riboswitches, and develop new hypotheses about corrinoid-specific physiology.Together, my research studies constitute a step towards reconciling the apparent oversimplicity of current cobalamin riboswitch models with the intrinsic complexity of the cellular processes they control.
일반주제명  
Microbiology.
일반주제명  
Molecular biology.
일반주제명  
Cellular biology.
키워드  
Cells
키워드  
Bacteria
키워드  
Corrinoids
키워드  
Cobalamin
키워드  
Cobalamin riboswitches
키워드  
Gene regulation
기타저자  
University of California, Berkeley Microbiology
기본자료저록  
Dissertations Abstracts International. 85-04B.
기본자료저록  
Dissertation Abstract International
전자적 위치 및 접속  
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MARC

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■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a576
■1001  ▼aKennedy,  Kristopher  J.
■24510▼aUncovering  How  Bacteria  Sense  and  Respond  to  Chemically  Diverse  Corrinoids  Through  Cobalamin  Riboswitch  Gene  Regulation▼h[electronic  resource]
■260    ▼a[S.l.]:▼bUniversity  of  California,  Berkeley.  ▼c2021
■260  1▼aAnn  Arbor  :▼bProQuest  Dissertations  &  Theses,  ▼c2021
■300    ▼a1  online  resource(102  p.)
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-04,  Section:  B.
■500    ▼aAdvisor:  Taga,  Michiko  E.
■5021  ▼aThesis  (Ph.D.)--University  of  California,  Berkeley,  2021.
■506    ▼aThis  item  must  not  be  sold  to  any  third  party  vendors.
■520    ▼aCells  actively  sense  and  integrate  information  about  their  internal  and  external  environments  to  execute  adaptive  physiological  responses.  This  makes  it  possible  to  survive  fluctuating  and  oftentimes  harsh  environmental  conditions.  Controlling  the  expression  of  genes  is  part  of  this  vital  cellular  process.  Indeed,  since  the  birth  of  molecular  biology  theory,  a  multitude  of  cellular  mechanisms  have  been  found  to  control  virtually  every  aspect  of  the  flow  of  genetic  information  from  DNA  to  RNA  to  functional  proteins.  The  revelation  that  RNAs  are  more  than  just  passive  messengers  between  DNA  and  proteins  was  a  turning  point  in  the  field  of  molecular  biology.  We  now  recognize  that  many  types  of  RNA  actively  fold  into  complex  three-dimensional  structures  to  carry  out  important  cellular  functions  with  sophistication,  precision,  and  efficiency  that  rivals  proteins.  A  prime  example  are  riboswitches  -  structured  noncoding  RNAs  that  sense  specific  small  molecule  effectors  by  direct  binding  and  function  as  cis-regulatory  genetic  switches.  My  dissertation  research  focuses  on  the  forms  and  functions  of  the  cobalamin  riboswitches  and  how  they  are  impacted  by  the  exceptional  chemical  diversity  of  naturally  occurring  variants  of  cobalamin  known  as  corrinoids.I  begin  the  first  chapter  with  a  broad  overview  of  bacterial  gene  regulation  with  specific  emphasis  on  mechanisms  of  transcriptional  and  translational  control.  This  sets  the  stage  for  delving  into  the  distinctive  elements  of  riboswitch  structure,  mechanism,  and  function.  I  also  describe  how  various  riboswitch  classes  connect  to  the  cellular  processes  which  they  control.  Lastly,  I  describe  in  detail  the  cobalamin  riboswitch  class  and  the  roles  that  corrinoids  play  in  bacterial  physiology.The  second  chapter  describes  the  bulk  of  my  endeavors  as  a  graduate  student  researcher  in  the  Taga  Lab  examining  the  corrinoid  specificity  of  cobalamin  riboswitches.  The  large  number  of  bacterial  metabolic  pathways  that  involve  corrinoids  and  the  numerous  types  of  corrinoid  cofactors  and  intermediates  present  a  puzzle  as  to  how  cells  can  effectively  use  cobalamin  riboswitches  to  control  their  corrinoid-related  physiology.  The  approach  I  took  leveraged  two  strengths  of  the  Taga  Lab's  expertise:  bacterial  molecular  genetics  and  biochemical  production  of  commercially  unavailable  corrinoid  molecules.  I  engineered  an  in  vivo  fluorescence  reporter  system  to  measure  the  responses  of  several  cobalamin  riboswitches  to  several  corrinoids.  From  the  patterns  of  corrinoid  selectivity  that  I  observed  in  my  experiments,  I  developed  a  mechanistic  hypothesis  for  corrinoid  specificity  of  cobalamin  riboswitch-based  gene  regulation  in  bacteria.  Furthermore,  I  propose  a  regulatory  strategy  that  attempts  to  explain  how  corrinoid  specificities  of  gene  regulation  and  bacterial  physiology  are  functionally  connected.In  the  third  chapter,  I  explore  the  functional  versatility  of  cobalamin  riboswitches.  As  the  second  most  prevalent  class  of  riboswitches,  I  speculated  that  novel  functional  variations  should  arise  from  the  diversity  of  cobalamin  riboswitch  sequences.  To  increase  the  likelihood  of  finding  uncommon  functional  variants,  I  focused  on  atypical  cobalamin  riboswitch  regulon  architectures  among  bacterial  species  that  specialize  in  corrinoid  metabolism.  This  rationale  enabled  me  to  successfully  identify  a  novel  activator  cobalamin  riboswitch,  dissect  modular  functionalities  of  tandemly  linked  cobalamin  riboswitches,  and  develop  new  hypotheses  about  corrinoid-specific  physiology.Together,  my  research  studies  constitute  a  step  towards  reconciling  the  apparent  oversimplicity  of  current  cobalamin  riboswitch  models  with  the  intrinsic  complexity  of  the  cellular  processes  they  control.
■590    ▼aSchool  code:  0028.
■650  4▼aMicrobiology.
■650  4▼aMolecular  biology.
■650  4▼aCellular  biology.
■653    ▼aCells
■653    ▼aBacteria
■653    ▼aCorrinoids
■653    ▼aCobalamin
■653    ▼aCobalamin  riboswitches
■653    ▼aGene  regulation
■690    ▼a0410
■690    ▼a0307
■690    ▼a0379
■71020▼aUniversity  of  California,  Berkeley▼bMicrobiology.
■7730  ▼tDissertations  Abstracts  International▼g85-04B.
■773    ▼tDissertation  Abstract  International
■790    ▼a0028
■791    ▼aPh.D.
■792    ▼a2021
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16931076▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.
■980    ▼a202402▼f2024

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