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Approaches and Applications for Targeted Phage Discovery
Approaches and Applications for Targeted Phage Discovery
Approaches and Applications for Targeted Phage Discovery

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20260202103512
ISBN  
9798280713673
DDC  
576
저자명  
Rand, Eleanor.
서명/저자  
Approaches and Applications for Targeted Phage Discovery
발행사항  
[Sl] : Harvard University, 2025
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2025
형태사항  
108 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
주기사항  
Advisor: Baym, Michael.
학위논문주기  
Thesis (Ph.D.)--Harvard University, 2025.
초록/해제  
요약Bacteriophages, phages for short, are viruses that infect bacteria. They are the most abundant biological entities on Earth and store a huge amount of genetic diversity. From this great diversity, we have gained insights ranging from fundamental biology to treatments for bacterial infections. Despite their importance across scientific and medical fields, techniques used to isolate phages from the environment have remained largely unchanged for nearly a century. In this work, I present a modification to the classic plaque assay to improve efficiency and information gained during phage screens and show its utility across multiple applications. This method involves co-culturing multiple, genetically distinct bacterial strains to identify phages based on differential lysis patterns. In the first half of the thesis, I demonstrate that the approach can distinguish between previously characterized phages with known receptor or defense system interactions. I then apply the same screening strategy to environmental samples and successfully isolate phages with desired characteristics. In the second half of the thesis, I deploy this screening method across four specific discovery projects. First, I identify phages dependent on diverse bacterial receptors and show that the method is especially useful when phage diversity in the sample is low. Second, I confirm the functionality of restriction enzyme homologs as phage defense systems by screening for phages they inhibit. Third, I identify candidate plasmid-dependent phages that appear to rely on a conjugative pilus encoded by an outbreak-associated IncX3 plasmid. Last, I isolate phages capable of infecting a genetically recoded bacterial strain by supplying the missing tRNAs. In addition to these biological findings, I include a parts list for the custom-built imaging system used to visualize fluorescent plaques. Collectively, this work offers a practical tool for improving phage discovery and contributes to our broader understanding of phage biology.
일반주제명  
Microbiology
일반주제명  
Biology
일반주제명  
Cellular biology
일반주제명  
Genetics
키워드  
Bacteriophage
키워드  
Fluorescence
키워드  
Bacterial infections
키워드  
Genetic diversity
키워드  
Bacterial strains
기타저자  
Harvard University Systems Biology
기본자료저록  
Dissertations Abstracts International. 86-12B.
전자적 위치 및 접속  
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■040    ▼aMiAaPQ▼cMiAaPQ
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■1001  ▼aRand,  Eleanor.▼0(orcid)0000-0003-0775-2064
■24510▼aApproaches  and  Applications  for  Targeted  Phage  Discovery
■260    ▼a[Sl]▼bHarvard  University▼c2025
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2025
■300    ▼a108  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-12,  Section:  B.
■500    ▼aAdvisor:  Baym,  Michael.
■5021  ▼aThesis  (Ph.D.)--Harvard  University,  2025.
■520    ▼aBacteriophages,  phages  for  short,  are  viruses  that  infect  bacteria.  They  are  the  most  abundant  biological  entities  on  Earth  and  store  a  huge  amount  of  genetic  diversity.  From  this  great  diversity,  we  have  gained  insights  ranging  from  fundamental  biology  to  treatments  for  bacterial  infections.  Despite  their  importance  across  scientific  and  medical  fields,  techniques  used  to  isolate  phages  from  the  environment  have  remained  largely  unchanged  for  nearly  a  century.  In  this  work,  I  present  a  modification  to  the  classic  plaque  assay  to  improve  efficiency  and  information  gained  during  phage  screens  and  show  its  utility  across  multiple  applications.  This  method  involves  co-culturing  multiple,  genetically  distinct  bacterial  strains  to  identify  phages  based  on  differential  lysis  patterns.  In  the  first  half  of  the  thesis,  I  demonstrate  that  the  approach  can  distinguish  between  previously  characterized  phages  with  known  receptor  or  defense  system  interactions.  I  then  apply  the  same  screening  strategy  to  environmental  samples  and  successfully  isolate  phages  with  desired  characteristics.  In  the  second  half  of  the  thesis,  I  deploy  this  screening  method  across  four  specific  discovery  projects.  First,  I  identify  phages  dependent  on  diverse  bacterial  receptors  and  show  that  the  method  is  especially  useful  when  phage  diversity  in  the  sample  is  low.  Second,  I  confirm  the  functionality  of  restriction  enzyme  homologs  as  phage  defense  systems  by  screening  for  phages  they  inhibit.  Third,  I  identify  candidate  plasmid-dependent  phages  that  appear  to  rely  on  a  conjugative  pilus  encoded  by  an  outbreak-associated  IncX3  plasmid.  Last,  I  isolate  phages  capable  of  infecting  a  genetically  recoded  bacterial  strain  by  supplying  the  missing  tRNAs.  In  addition  to  these  biological  findings,  I  include  a  parts  list  for  the  custom-built  imaging  system  used  to  visualize  fluorescent  plaques.  Collectively,  this  work  offers  a  practical  tool  for  improving  phage  discovery  and  contributes  to  our  broader  understanding  of  phage  biology.
■590    ▼aSchool  code:  0084.
■650  4▼aMicrobiology
■650  4▼aBiology
■650  4▼aCellular  biology
■650  4▼aGenetics
■653    ▼aBacteriophage
■653    ▼aFluorescence
■653    ▼aBacterial  infections
■653    ▼aGenetic  diversity
■653    ▼aBacterial  strains
■690    ▼a0410
■690    ▼a0306
■690    ▼a0379
■690    ▼a0369
■71020▼aHarvard  University▼bSystems  Biology.
■7730  ▼tDissertations  Abstracts  International▼g86-12B.
■790    ▼a0084
■791    ▼aPh.D.
■792    ▼a2025
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357437▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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