A roadmap for greater science diversity at UO (Guest opinion)

The Oregonian  

2017-06-11

Most people confronted with the innards of a gutted fish will recoil in disgust. But as scientists who study the microbial communities, or microbiomes, of animals, we are fascinated by the tiny critters that make their home inside a fish gut. Through our own research on the zebrafish, we know that some of these microbes hold the promise for bettering human health, from stimulating the production of insulin-secreting cells in a pancreas to soothing an overactive immune system...

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UO’s Knight Campus gets first hearing in state Legislature

Around the O  online

2017-03-28

Speaking at the hearing were Patrick Phillips, acting executive director of the Knight Campus; Karen Guillemin, professor of biology and one of the faculty members who developed the initiative; and Michelle Sconce, a graduate teaching fellow and student of Guillemin. A recording of the hearing can be viewed on the Oregon Legislature's website.

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Pursuing a Hunch

Around the O  online

2016-12-19

“The fact that we only found one protein that fit our criteria was actually kind of disappointing,” Hampton Hill said. “In science, it’s so rare to have one candidate that works. I thought I’d have to do a lot more work.” Hampton Hill’s advisor, UO biologist Karen Guillemin, recalls her own skeptical response. “I said, ‘There’s no way that this is it, Jen,’” Guillemin said. “This is just too good to be true.” Further testing confirmed the results and months of additional research followed. Guillemin and Hampton Hill compiled their findings in a just-published research paper in the open access journal eLife.

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UO finds bacterial protein that boosts insulin-producing cells in zebrafish

Around the O  online

2016-12-13

The research demonstrates the developmental role of teeming communities of bacteria and other microbes — the microbiota — in the bodies of animals, said UO biologist Karen Guillemin, a co-author. Understanding how the microbiota affects the development of beta cells, which are lost in patients with Type 1 diabetes, eventually could lead to new diagnostic, preventative and therapeutic approaches for this disease, she said.

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Bacteria that boost insulin-producing cells could yield new diabetes approaches

Fierce Biotech  

2016-12-16

The key will be to figure out how gut bacteria—known by scientists as microbiota—impact beta cell development, said Karen Guillemin, a biologist at the University of Oregon and co-author of a paper about the discovery published in eLife. "We're realizing that the microbiome is a rich source for discovering new biomolecules that have enormous potential for manipulating and promoting our health," she said in a press release from the university...

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The Enteric Nervous System Promotes Intestinal Health by Constraining Microbiota Composition

Rolig, A. S., E. K. Mittge, J. Ganz, J. V. Troll, E. Melancon, T. J. Wiles, K. Alligood, W. Z. Stephens, J. S. Eisen, and K. Guillemin.

2017 Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health.

A Conserved Bacterial Protein Induces Pancreatic Beta Cell Expansion During Zebrafish Development

Hill, J. H., E. A. Franzosa, C. Huttenhower, and K. Guillemin

2016 Resident microbes play important roles in the development of the gastrointestinal tract, but their influence on other digestive organs is less well explored. Using the gnotobiotic zebrafish, we discovered that the normal expansion of the pancreatic β cell population during early larval development requires the intestinal microbiota and that specific bacterial members can restore normal β cell numbers. These bacteria share a gene that encodes a previously undescribed protein, named herein BefA (β Cell Expansion Factor A), which is sufficient to induce β cell proliferation in developing zebrafish larvae. Homologs of BefA are present in several human-associated bacterial species, and we show that they have conserved capacity to stimulate β cell proliferation in larval zebrafish. Our findings highlight a role for the microbiota in early pancreatic β cell development and suggest a possible basis for the association between low diversity childhood fecal microbiota and increased diabetes risk.

Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota.

Wiles, T. J., M. Jemielita, R. P. Baker, B. H. Schlomann, S. L. Logan, J. Ganz, E. Melancon, J. S. Eisen, K. Guillemin, and R. Parthasarathy

2016 The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this “microbial organ” for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this issue, we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within a vertebrate gut. We observed that the interplay between each population and the gut environment produces distinct spatiotemporal patterns. As a consequence, one species dominates while the other experiences sudden drops in abundance that are well fit by a stochastic mathematical model. Modeling revealed that direct bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to a mutation in the ret locus, which in humans is associated with the intestinal motility disorder known as Hirschsprung disease. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities can drive bacterial population dynamics within the gut, and it reveals a new facet of the intestinal host–microbe interface by demonstrating the capacity of the enteric nervous system to influence the microbiota. Ultimately, these findings suggest that therapeutic strategies targeting the intestinal ecosystem should consider the dynamic physical nature of the gut environment.

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Individual Members of the Microbiota Disproportionately Modulate Host Innate Immune Responses.

Rolig, A. S., R. Parthasarathy, A. R. Burns, B. J. Bohannan, and K. Guillemin

2015 Predicting host health status based on microbial community structure is a major goal of microbiome research. An implicit assumption of microbiome profiling for diagnostic purposes is that the proportional representation of different taxa determine host phenotypes. To test this assumption, we colonized gnotobiotic zebrafish with zebrafish-derived bacterial isolates and measured bacterial abundance and host neutrophil responses. Surprisingly, combinations of bacteria elicited immune responses that do not reflect the numerically dominant species. These data are consistent with a quantitative model in which the host responses to commensal species are additive but where various species have different per capita immunostimulatory effects. For example, one species has a high per capita immunosuppression that is mediated through a potent secreted factor. We conclude that the proportional representation of bacteria in a community does not necessarily predict its functional capacities; however, characterizing specific properties of individual species offers predictive insights into multi-species community function.

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What Is the Future of Developmental Biology?

Guillemin, K.

2017 In the pre-molecular era, experimental embryology defined the concepts of induction, morphogen gradients, and signaling centers. In the 1980s, developmental genetics identified the genes and signaling cascades that underlie these concepts. A multitude of papers described how a handful of signaling pathways shape every organ. The joke was that there are two types of developmental biologists: those who know they work on Notch (or Hedgehog, BMP, or Wnt) and those who don’t. This became repetitive, which seriously hurt the field.

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The Scales of the Zebrafish: Host-microbiota Interactions From Proteins to Populations

Burns, A. R., Guillemin, K.

2017 The interactions between animal hosts and their associated microbiota can be studied at multiple spatial and conceptual scales, with each providing unique perspectives on the processes structuring host-microbe systems. Recently, zebrafish, Danio rerio, has emerged as a powerful model in which to study these interactions at many different scales. Controlled but simplified gnotobiotic experiments enable discovery of the molecules and cellular dynamics that shape host-microbe system development, whereas population level investigations of bacterial dispersal and transmission are beginning to reveal the processes shaping microbiota assembly across hosts. Here we review recent examples of these studies and discuss how the results can be integrated to better understand host-microbiota systems.