Award Abstract # 1233760
Understanding the Effects of Complex Phage-Bacteria Infection Networks on Marine Ecosystems

NSF Org: OCE
Division Of Ocean Sciences
Recipient: GEORGIA TECH RESEARCH CORP
Initial Amendment Date: August 1, 2012
Latest Amendment Date: August 1, 2012
Award Number: 1233760
Award Instrument: Standard Grant
Program Manager: David Garrison
OCE
 Division Of Ocean Sciences
GEO
 Directorate For Geosciences
Start Date: August 15, 2012
End Date: February 28, 2017 (Estimated)
Total Intended Award Amount: $471,076.00
Total Awarded Amount to Date: $471,076.00
Funds Obligated to Date: FY 2012 = $471,076.00
History of Investigator:
  • Joshua Weitz (Principal Investigator)
    jsweitz@umd.edu
Recipient Sponsored Research Office: Georgia Tech Research Corporation
926 DALNEY ST NW
ATLANTA
GA  US  30318-6395
(404)894-4819
Sponsor Congressional District: 05
Primary Place of Performance: Georga Institute of Technology
225 North Ave NW
Atlanta
GA  US  30332-0002
Primary Place of Performance
Congressional District:
05
Unique Entity Identifier (UEI): EMW9FC8J3HN4
Parent UEI: EMW9FC8J3HN4
NSF Program(s): BIOLOGICAL OCEANOGRAPHY
Primary Program Source: 01001213DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 0000
Program Element Code(s): 165000
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.050

ABSTRACT

Bacteria and their viruses (phages) make up two of the most abundant and genetically diverse groups of organisms in the oceans. The extent of this diversity has become increasingly apparent with the advent of environmental sequencing. However, the ongoing discovery of new taxonomic diversity has, thus far, out-paced gains in quantifying the function of and interactions among phages and bacteria. Improved quantitative understanding of how diverse groups of phages exploit bacterial hosts will improve predictions of microbial population dynamics, ecosystem functioning, and the large-scale dynamics of global biogeochemical cycles. This project will develop a theoretical framework for characterizing the effect of complex phage-bacteria interactions on marine ecosystem structure and function. The theoretical framework is grounded in the analysis of cross-infection assays of bacteriophages with their bacterial hosts, termed phage-bacteria infection networks (PBINs). Recent discoveries concerning the structure of PBINs will be combined with a novel eco-evolutionary dynamics modeling framework in the service of the following aims: Aim 1. Develop theoretical methods to analyze PBINs that include quantitative infection data to characterize complex patterns of cross-infection found in marine ecosystems.
Aim 2. Establish eco-evolutionary multi-strain models that incorporate complex PBIN data to evaluate hypotheses regarding how cross-infection within PBINs affects community stability.
Aim 3. Utilize the multi-strain model to predict how PBINs influence: (i) the ratio of viral to bacterial population abundances; and (ii) the flux of carbon and nutrients at the ecosystem level.

The theory developed in this project will improve characterizations of phage- bacteria interactions in marine ecosystems and establish a framework to link phage-bacteria in- teractions with ecosystem function. First, the project will generalize preliminary findings of multi-scale structure within empirical PBINs by developing novel network theories that can be applied to quantitative infection data. Properties of marine PBINs will be analyzed to assess whether they are hierarchically organized, organized into modules, and/or possess multi-scale structure. The statistical structure of PBINs will be integrated with multi-scale coevolutionary models. These co- evolutionary models will be utilized to evaluate hypotheses regarding how cross-infection structure affects community stability. Finally, these coevolutionary models will be used to consider carbon and nutrient regeneration via viral lysis of bacterial hosts. PBIN structure will be varied to establish a link between cross-infection and key indices of ecosystem structure and function, with specific applications to Roseobacter and Synechococcus hosts. Analytical methods and large-scale simulations will be utilized to achieve these goals, closely linked to empirical datasets.

Broader impacts: Educational objectives will be centered around the theme of fostering the next generation of quantitative biologists interested in microbial systems (Aim 4). In doing so, the PI will: (i) provide a training program for quantitative biologists that enables them to have direct interactions with students of different backgrounds; (ii) introduce a new course focusing on quantitative viral ecology; (iii) develop and disseminate software tools that enable biologists to apply rigorous quantitative methods to viral-host interaction data and to the study of viral-host communities. Two graduate students and eight undergraduates will be directly supported on this project. These students will have academic backgrounds spanning physics to biology and work in collaborative teams. The graduate students will travel for extended visits to the viral ecology laboratories at the U of Arizona and U of Tennessee-Knoxville. A new graduate course will be developed on quantitative viral ecology to serve trainees on this grant and the growing number of students interested in environmental microbiology at Georgia Tech. The theories developed in this project will be implemented and disseminated as open-source software tools.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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(Showing: 1 - 10 of 11)
Jover LF, Cortez MH, and Weitz, JS "Mechanisms of multi-strain coexistence in host-phage systems with nested infection networks" Journal of Theoretical Bilogy , v.inpress , 2013 , p.inpress 10.1016/j.jtbi.2013.04.011
L.F. Jover, M.H. Cortez and J.S. Weitz "Mechanisms of multi-strain coexistence in host-phage systems with nested infection networks." J. Theoretical Biology , v.332 , 2013 , p.65
L.F. Jover, T.C. Effler, A. Buchan, S.W. Wilhelm and J.S. Weitz "The elemental composition of virus particles: implications for marine biogeochemical cycles" Nature Reviews Microbiology , 2014
Li Deng, J. Cesar Ignacio-Espinoza, Ann Gregory, Bonnie T. Poulos, Joshua S. Weitz, Philip Hugenholtz, Matthew B. Sullivan. "Viral tagging reveals discrete populations in Synechococcus viral genome sequence space" Nature , 2014
Cesar Flores, Tim Poisot, Sergi Valverde and Joshua S. Weitz "BiMat: a MATLAB package to facilitate the analysis of bipartite networks" Methods in Ecology and Evolution , v.7 , 2016 , p.127 10.1111/2041-210X.12458
Charles H Wigington, Derek L Sonderegger, Corina PD Brussaard, Alison Buchan, Jan F Finke, Jed Fuhrman, Jay T Lennon, Mathias Middelboe, Curtis A Suttle, Charles Stock, William H Wilson, K Eric Wommack, Steven W Wilhelm, Weitz, J.S "Re-examination of the relationship between marine virus and microbial cell abundances" Nature Microbiology , v.1 , 2016 , p.15024 10.1038/nmicrobiol.2015.24
Taylor, B.P. and Penington, C.J. and Weitz, J.S. "Emergence of increased frequency and severity of multiple infections by viruses due to spatial clustering of hosts" Physical Biology , v.13 , 2016 , p.066014 10.1088/1478-3975/13/6/066014
Luis F. Jover, Cesar O. Flores, Michael H. Cortez & Joshua S. Weitz "Multiple regimes of robust patterns between network structure and biodiversity" Scientific Reports , v.5 , 2015 , p.17856 10.1038/srep17856
Jover, Luis F. and Romberg, Justin and Weitz, Joshua S. "Inferring phage-bacteria infection networks from time-series data" Royal Society Open Science , v.3 , 2016 10.1098/rsos.160654
Jover LF, Cortez MH, Weitz JS. "Mechanisms of Multi-strain Coexistence in Host-Phage Systems with Nested Infection Networks" Journal of Theoretical Biology , v.332 , 2013 , p.65
Joshua S Weitz, Charles A Stock, Steven W Wilhelm, Lydia Bourouiba, Maureen L Coleman, Alison Buchan, Michael J Follows, Jed A Fuhrman, Luis F Jover, Jay T Lennon, Mathias Middelboe, Derek L Sonderegger, Curtis A Suttle, Bradford P Taylor, T Frede Thingst "A multitrophic model to quantify the effects of marine viruses on microbial food webs and ecosystem processes." ISME J , 2015 10.1038/ismej.2014.220
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PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

In the oceans, viruses are both highly abundant and diverse, e.g., there are typically over a 10 billion viruses in a liter of surface seawater.  Yet the vast majority of these viruses don’t make humans sick. Instead, most of these viruses infect ocean microbes.  This NSF Biological Oceanography project led by Joshua Weitz (Professor of Biological Sciences, Georgia Tech), set out to understand how viruses affect life and biogeochemistry in the global oceans.  

Specifically, this project enabled a multi-year effort to understand which microbes get sick by which viruses, how microbes and viruses persist, and how ocean ecosystems respond to infections taking place at the base of the ocean’s food web. Via collaboration with researchers in the USA and internationally, we characterized datasets and models of cross-infection and their consequences. 

First, we expanded upon earlier reports that viruses are not just specialists. That is, viruses can infect many more than one type of bacteria.  Similarly, bacteria can be infected by many more than one type of virus.  Through a systematic network approach, we identified patterns of cross-infection that can be found in highly disparate communities.  This cross-infectivity raises the question: which “strategy” is favored, i.e., is it evolutionarily favorable to be a specialist or a generalist for viruses?  We found that the answer is context-dependent. We also developed models to show how such cross-infection could persist given trade-offs between infecting hosts vs. persisting in the oceans outside hosts. 

Yet the consequences of viral infection has many indirect effects.  When a virus kills a microbial cell, the remains of the cell may be consumed by other microbes.  This is known as the “viral shunt” in the sense that carbon and other nutrients are shunted away from larger organisms that move material up the food chain. In this project, we developed quantitative models of the elemental content and requirements of viruses. As a consequence, we were able to develop a quantitative, mechanistic model revealing how viruses may kill individual cells but indirectly enhance productivity of the community. Collaborating with Steven Wilhelm (UT-Knoxville) and others, we also contested the paradigm that there are 10 viruses per microbe in the ocean. Instead, by re-analyzing data from multiple oceanic expeditions, we found that the average number of viruses per microbe tends to decreases in environments with more microbes.

The analysis of virus-microbe interactions and their consequences was enabled by development of computational models and simulations.  In the latter stages of the project we developed a community resource tool, BiMAT, to facilitate analysis of interaction networks, including those between viruses and microbes.  This tool is available as an open-source library for the community. In addition, all other models in the project, including a new approach to infer networks from time series data, were released via the Weitz group’s GitHub page.

The contributions within and between disciplines was facilitated by the contributions of multiple undergraduate and graduate students.  Two REU students were supported in the project. In addition, three Ph.D. students were partially supported by this grant.  All three graduated with Ph.D.-s in Physics, albeit with application to the biology of virus-host interactions in the oceans.  Two of these students moved directly into industry. One is now a postdoctoral fellow. In total, 10 new peer-reviewed articles were published as a direct result of support enabled by this project.

The research discoveries in this project directly facilitated a series of efforts that resulted in broader impacts. First, leveraging discoveries and insights, Joshua Weitz wrote a 360 page monograph on Quantitative Viral Ecology. This book was published in December 2015 by Princeton University Press and was awarded the 2016 Best Postgraduate Textbook Prize from the Royal Society of Biology (London, UK).  The book includes multiple chapters underlying the quantitative study of virus-microbe interactions and their consequences, as well as capstone chapters focusing on ocean viruses. 

In addition, Weitz collaborated with Steven Wilhelm (UT-Knoxville) to co-author a perspective on Ocean Viruses published in the New Scientist in 2013. Weitz and his group have also been active in presenting their research in US universities, at international institutions, disciplinary conferences (like the Aquatic Viral Workshop), to conferences focusing on other disciplines (like the American Physical Society annual meeting), and to the general public. Of note, Weitz was the featured speaker in the September 2016 “Atlanta Science Tavern” event on the theme of “Microbes Get Sick, Too”.


Last Modified: 04/30/2017
Modified by: Joshua S Weitz

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