The microorganisms of the human intestinal tract-known as the 'microbiota'-represent a dynamic and diverse community made up of over 500 species and 100 trillion cells. Advancements in genomics over the last decade have greatly facilitated the characterization of this complex multi-species symbiont. It has been found that phylum-level compositional shifts in the microbiota, which can be induced by environmental, host and bacterial factors, correlate with and promote human disease. The next frontier in this research field is to understand how potentially deleterious shifts in the microbiota occur and how such shifts might be corrected to treat disease. Herein I describe a systems biology approach to identify molecular and cellular determinants of microbiota robustness (resistance to perturbation) and resilience (recovery from perturbation). The overarching hypothesis guiding my research plan is that both bacteria and host-derived properties contribute to the compositional integrity of the microbiota. To address this hypothesis, I will employ a gnotobiotic zebrafish host model system that is amenable to high-throughput and real time investigation of host-associated microbial community dynamics.
AIM 1 of my proposal will identify bacterial genes within a natural zebrafish bacterial isolate required to resist the colonization of an invasive species.
AIM 2 will address the consequences of temporary host immunosuppression on the diversity and function of the microbiota. And in AIM 3 I will investigate the role of specie extinction events, which can be a consequence of antibiotic use, on the composition and function of the microbiota. Observations made during this work will inform the design of more effective probiotic and therapeutic regimes for treating diseases associated with pathogenic alterations of the microbiota.

Public Health Relevance

The composition and functional properties of an individual's microbiota can influence their predisposition to a variety of disorders, including obesity, diabetes, colon cancer and intestinal bowel disease. The goal of my research is to identify bacterial and host factors that underlie the ability of the microbiota to resist and recover from perturbation. This work will inform the design of therapeutic interventions aimed at treating disease through manipulation of the microbiota.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AI112094-01
Application #
8716351
Study Section
Special Emphasis Panel (ZRG1-F13-C (21))
Program Officer
Prograis, Lawrence J
Project Start
2014-02-01
Project End
2017-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$49,214
Indirect Cost
Name
University of Oregon
Department
Biochemistry
Type
Organized Research Units
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403