Research Summary

Human health is intimately connected to our microbiota, a constantly-evolving consortium of trillions of bacteria that live on and within us, producing compounds that provide nourishment and affecting myriad functions including immunity and neurodevelopment. Our bodies and our surroundings are composed of diverse environments with widely different physical and chemical properties, including water availability, salt concentration, acidity, and temperature. These properties strongly influence which microbes will colonize and survive in, on, and outside our bodies. Our laboratory combines cutting-edge experimental and computational techniques to study how these properties affect the microbiota, and transmission of bacteria between hosts in health and disease.

More than 20 million Canadians suffer every year from digestive disorders involving the gut microbiota. The varying abiotic intestinal microenvironment (pH, osmolality, mucus availability) seen in these diseases restricts the ability of certain bacteria to grow in the gut, greatly modifying the microbial community. The mechanisms of bacterial resilience to these common environmental shifts are not understood. The long-term goal of our research program is to determine the mechanisms by which microbial communities remain resilient during disturbances (perturbations) in their physical (abiotic) environment. 

Projects

1)      Osmotic diarrhea is a prevalent condition, caused by food intolerance, celiac disease, and widespread use of laxatives. Previous work has shown that, during osmotic diarrhea, there is increased susceptibility to infection by pathogens, indicating that disrupted abiotic conditions may have detrimental effects on key microbiota functions, including colonization resistance. In previous work we have shown that osmotic diarrhea disrupts the colonic environment, leads to extinction of key bacterial families, and decreases microbial diversity. We seek to discover the mechanisms involved in microbiota resilience to osmotic perturbation due to osmotic diarrhea by determining the behavior of key microbial families in clinical samples and then testing specific mechanisms in the laboratory.

2)      One of the ways that bacterial community dynamics are affected during abiotic perturbations is through changes in the infective and reproductive abilities of viruses that infect bacteria, known as bacteriophages or phages. Although phages are the most abundant organisms on Earth, we know very little about the complexities of the relationship between them and their bacterial hosts, particularly in the context of abiotic perturbations. Understanding the molecular mechanisms underlying this interaction is essential to understanding microbial communities associated with various hosts and environments. Our lab aims to unravel the bacterial as well as phage-dependent mechanisms by which phage infection is resilient to environmental perturbations.

3)   The varying abiotic intestinal microenvironment (pH, osmolality, mucus availability) in inflammatory bowel disease (IBD) restricts the ability of certain bacteria to grow in the gut, thereby limiting fecal microbiota transplant (FMT) efficacy. We know very little about the mechanisms of interplay between the gut microbiota and abiotic environmental conditions in IBD. Our objectives are therefore to 1) determine how the IBD microbiota changes the abiotic gut environment and 2) predict and engineer the ability of microbial members from healthy subjects to colonize an altered IBD gut environment and ameliorate it. By characterizing the luminal environment (pH, osmolality, mucus and bacterial components) from IBD models and human biopsies and using in vitro and bioengineering approaches combined with computational analysis we aim to create a predictive model of the interplay between gut environment and microbial communities in IBD. This understanding is necessary to improve treatment efficacy and to develop novel personalized IBD therapies. 

 

Bio

B. Sc., University of British Columbia (Honors Biophysics)

Ph.D., Stanford University (Biophysics)

Postdoctoral Fellow, Stanford University (Microbiology and Immunology)

Awards

James S. McDonnell Foundation Postdoctoral Fellowship Award (2014–2017)

Stanford Bio-X Interdisciplinary Graduate Fellowship – Bruce and Elizabeth Dunlevie (2011–2014)

Stanford Graduate Fellowship (2008-2011)

Publications

Google scholar link:https://scholar.google.ca/citations?user=_V-I0aMAAAAJ&hl=en

1.      Tabula Muris Consortium. “Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris.” 562(7727):367-372. Oct 2018. Nature

2.      C. Tropini, E. L. Moss, K. Ng, S. K. Higginbottom, E. P. Casavant, C. G. Gonzales, B. Fremin, J. E. Elias, K. C. Huang, A. S. Bhatt, and J. L. Sonnenburg. “Transient osmotic perturbation causes long-term alteration to the gut microbiota”. 173(7):1742-1754, June 2018, Cell.

3.      C. Tropini*, K. Earle*, K. C. Huang, J. L. Sonnenburg. “The Gut Microbiome: Connecting Spatial Organization to Function. 21:433–442, April 2017. Cell Host and Microbe.

4.      C. Tropini, T. K. Lee, J. Hsin, S. Desmarais, T. Ursell, R. Monds, K. C. Huang. “General principles of bacterial cell-size determination revealed by heterologous expression of cell wall synthesis machinery and chemical perturbations”. Vol. 9, 1520-1527. November 2014. Cell Reports.

5.      B. A. Krajina, C. Tropini, A. Zhu, P. DiGiacomo, J. L. Sonnenburg, S. C. Heilshorn, and A. J. Spakowitz. “Dynamic light scattering microrheology reveals multi-scale viscoelasticity of polymer gels and precious biological materials”. 10.1021/acscentsci.7b00449, December 2017. ACS Central Science.

6.      K. Heyries, C. Tropini, M. VanInsberghe, O.I. Petriv, C. Hugesman, A. Singhal, K. Leung, C.L. Hansen. “Megapixel Digital PCR”, Vol. 8, 649-651. July 2011, Nature Methods.

7.      Y. E. Chen*, C. Tropini*, K. Jonas, C. G. Tsokos, K. C. Huang, M. T. Laub “Spatial gradient of protein phosphorylation underlies replicative asymmetry in a bacterium” Vol. 108(3), 1052-1057. January 2011, PNAS. *Co-first author

8.      C. Tropini and K. C. Huang. “Interplay between the Localization and Kinetics of Phosphorylation in Flagellar Pole Development of the Bacterium Caulobacter crescentus”. Vol, 8(8), e1002602. August 2012, Plos Computational Biology.

9.      C. Tropini, N. Rabbani and K. C. Huang. Physical constraints on the establishment of intracellular spatial gradients in bacteria”. Vol. 5(1), 17, August 2012, BMC Biophysics.

10.  C. Tropini and A. Marziali, “Multi-nanopore force spectroscopy for DNA analysis” Vol. 92, 1632-1637. March 2007, Biophysical Journal.

 

 

 

 

 

 

 

 

 

 

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