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Flow cytometric characterization of B cell development in mouse strains expressing unmutated common ancestors of HIV-1 broadly neutralizing antibodies

Flow cytometric characterization of B cell development in mouse strains expressing unmutated common ancestors of HIV-1 broadly neutralizing antibodies

Project Summary

After several years of HIV-1 infection, some patients develop broadly neutralizing antibodies to the HIV-1 envelope protein. These antibodies are extensively mutated, suggesting multiple rounds of selection within germinal centers, yet these antibodies arose from an unmutated common ancestor which presumably bound HIV-1. The Cain Lab is interested in characterizing B cell development in a series of transgenic mice expressing the unmutated common ancestor (“UCA”) of different HIV-1 broadly neutralizing antibodies. Interestingly, B cell development is impacted to varying degrees across the different UCA-expressing mouse strains, suggesting that mechanisms of immunological tolerance may inhibit the production of B cell lineages with the potential to bind HIV-1. The overall goal of this internship is to use flow cytometry to compare B cell development across the various UCA-expressing mouse strains, and identify in each strain the developmental stages at which tolerance mechanisms act. I am looking for an intern with a background in statistics, computer science, or math to develop a pipeline for analyzing high-parameter flow cytometry data that includes dimension reduction tools such as t-SNE (t-Distributed Stochastic Neighbor Embedding) and SPADE (Spanning tree Progression Analysis of Density-normalized Events).

Timeline:

  • Weeks 1-3: Review literature on flow cytometric characterization of mouse B cell development; review learn algorithms for dimensional reduction of high-parameter cytometry data.
  • Weeks 4-5: Develop a strategy for dimensional reduction of high-parameter flow cytometry data using t-SNE and SPADE.
  • Weeks 6-10: Apply dimension reduction strategy to flow cytometry data for 8-10 UCA transgenic mouse strains.

Desired Outcome:

  • SPADE Trees depicting B cell development in 8-10 UCA transgenic mouse lines Special Project Features
  • The intern will work at the cutting edge of HIV research.
  • The intern will be a member of a team pushing the envelope of flow cytometry analysis.
  • The intern will meet weekly with the PI for mentoring, data strategizing, and discussion.

Expectations for intern

  • Familiarity with flow cytometry
  • Experience with FlowJo and/or Cytobank OR be able to construct processing pipelines using R/Bioconductor