Massively parallel combinatorial microbiology

Reductionist biology of the 20th century rooted pure culture methods and antibiotics as pillars of humankind's interaction with microbiology, igniting a revolution in medicine and biotechnology. The revolution was not without cost. By overlooking complex biological interactions, it introduced new problems--from the sharp rise in immune disorders to the antibiotic resistance crisis--that 21st century tools must address. While 'omics methods have fundamentally expanded our understanding of biological complexity, we lack a generalized method for measuring how the parts of a complex system, such as the individual strains of a microbial community, interact with each other. In this thesis, I present kChip, a new platform for constructing massively parallel combinatorial arrays of these parts in order to measure their interactions directly. I describe how kChip has been used to reveal patterns in microbial community assembly, unearth minimal microbial combinations with desirable functions, and screen for compounds that potentiate antibiotic activity. I demonstrate how kChip can advance the development of new technologies like microbial consortia and combinatorial drug therapies.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biological Engineering

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Kehe, Jared Scott.

Advisor dc:contributor.advisor

• Paul C. Blainey.

• Biological Engineering.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/127886

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/127886