A single-cell perspective on infection
Thesis: Ph. D. in Bioinformatics, Harvard-MIT Program in Health Sciences and Technology, 2016.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2016
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| Online Access: | http://hdl.handle.net/1721.1/103500 |
| _version_ | 1811071101266034688 |
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| author | Haseley, Nathan Scott |
| author2 | Deborah T. Hung. |
| author_facet | Deborah T. Hung. Haseley, Nathan Scott |
| author_sort | Haseley, Nathan Scott |
| collection | MIT |
| description | Thesis: Ph. D. in Bioinformatics, Harvard-MIT Program in Health Sciences and Technology, 2016. |
| first_indexed | 2024-09-23T08:46:05Z |
| format | Thesis |
| id | mit-1721.1/103500 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T08:46:05Z |
| publishDate | 2016 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1035002019-04-10T07:26:27Z A single-cell perspective on infection Haseley, Nathan Scott Deborah T. Hung. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Thesis: Ph. D. in Bioinformatics, Harvard-MIT Program in Health Sciences and Technology, 2016. Cataloged from PDF version of thesis. Includes bibliographical references (pages 83-94). The clinical course of infection is ultimately determined by a series of cellular interactions between invading pathogens and host immune cells. It has long been understood that these interactions, even when they occur in tissue culture models, give rise to a wide variety of different outcomes, some beneficial to the host, others to the pathogen. These cellular interactions, however, are typically studied at a bulk level; masking this cell-to-cell variation, losing important information about the full range of possible host-pathogen interactions, and leaving the mechanistic basis for these different outcomes largely unexplored. Here, we present a system that combines single-cell RNA sequencing with fluorescent markers of infection outcome to directly correlate host transcription signatures with infection outcome at the single cell level. Applying this system to the well-characterized model of Salmonella enterica infection of mouse macrophages, we found: 1) Unique transcription signatures associated with bacterial exposure and bacterial infection, 2) Sustained high levels of heterogeneity in immune pathways in infected macrophages, and 3) A novel subpopulation of macrophages characterized by high expression of the Type I Interferon response after infection. Upon further investigation we found that this heterogeneity in the host Type I Interferon response was the result of heterogeneity in the population of infecting bacteria, namely in the extent of PhoPQ-mediated LPS modifications. This work highlights the importance of heterogeneity as a characteristic of bacterial populations that can influence the host immune response. It also demonstrates the benefits of examining infection with single-cell resolution. by Nathan Scott Haseley. Ph. D. in Bioinformatics 2016-07-01T18:45:59Z 2016-07-01T18:45:59Z 2016 2016 Thesis http://hdl.handle.net/1721.1/103500 952429310 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 116 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Harvard--MIT Program in Health Sciences and Technology. Haseley, Nathan Scott A single-cell perspective on infection |
| title | A single-cell perspective on infection |
| title_full | A single-cell perspective on infection |
| title_fullStr | A single-cell perspective on infection |
| title_full_unstemmed | A single-cell perspective on infection |
| title_short | A single-cell perspective on infection |
| title_sort | single cell perspective on infection |
| topic | Harvard--MIT Program in Health Sciences and Technology. |
| url | http://hdl.handle.net/1721.1/103500 |
| work_keys_str_mv | AT haseleynathanscott asinglecellperspectiveoninfection AT haseleynathanscott singlecellperspectiveoninfection |