Reflections on the National Science Foundation's Understanding the Rules of Life Program Proceedings of a Workshop Series (2023) / Chapter Skim
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2 URoL: Microbiome
Pages 21-36

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From page 21...
... A third program, URoL:Emergent Networks (URoL:EN) ,3 published in 2021, is a crossdirectorate program of NSF that includes some microbiome research.
From page 22...
... described his group's URoL:MTM project, which investigates the microbiome dynamics within marine fish species. The group specifically aims to contrast fish with two different feeding ecologies -- coastal pelagic herbivorous versus cosmopolitan herbivorous.5 Microbiome samples are characterized across multiple body sites via metagenomic analysis and cultivated in vitro.
From page 23...
... In response to a question from Handelsman regarding the source of the gut symbionts, most of which are not present in seawater, Allen replied that it is a combination of vertical transmission, sediment (in demersal fish) , and coprophagy, which occurs when schooling fish eat the feces of their neighbors, "doing their own little aquatic fecal transplant." The gut exerts strong selective pressure for the growth of key taxa that contribute to host physiology.
From page 24...
... These differ considerably in microbiome complexity, ranging from a single non-pathogenic bacterial parasite that dominates the coral microbiome, 40-100 bacterial species in zebrafish gut, and a much more diverse microbiome in the seagrass. The exact same experiment is conducted in each system.
From page 25...
... On the data analysis side, the researchers found that of the multiple types of -omics they have analyzed by deep learning (metagenomics, metatranscriptomics, 16s RNA, and metabolomics) , microbial metabolomics showed the best correlation with host phenotype.
From page 26...
... The relative involvement of stochastic versus deterministic processes may itself vary among systems and situations, noted Martiny and McFall-Ngai, who suggested that if a spectrum exists between these two mechanisms in the microbiome biosphere, then there may be rules that govern its application. Another goal, that of identifying a microbial signature that underlies transient microbiome dynamics, faces both theoretical and measurement challenges, said Zhou.
From page 27...
... . Her group will combine intensive field observations spanning multiple seasons with laboratory experiments, -omics investigations, and bioinformatics to develop a predictive model of the timing of benthic anatoxin-producing mats in streams in northern California.
From page 28...
... In a similar vein, although Thacker's previous observations highlighted sponges with unique, species-associated microbiomes that were vertically transmitted to the larvae, suggesting co-speciation, more recent work in other sponges has uncovered considerable evidence of host switching and acquisition from the environment. This has caused him to rethink the role of cophylogeny in the sponge-microbiome relationship.
From page 29...
... A URoL PI who was unable to attend the meeting referenced work they had recently published "showing that genomes can be used to predict emergent community metabolism" and illustrating an emergent rule that "gene presence and absence can predict metabolite dynamics." Impacts of Microbiome on Resilience to Disturbance It is a tenet of ecological theory that diversity within an ecosystem increases its resistance to disturbance. In a large modeling experiment of coral microbiomes across coral phylogeny, Vega Thurber's group found that, once host phylogeny was disentangled from the microbiome, ecological dominance was the primary driver of disease phenotype.
From page 30...
... Quantification and sensitivity also present technical issues, "so we should be very, very careful when we address research questions using omics tools. One critical question is whether the data quality is good enough." He said that his group has frequent discussions about the extent to which experimentally-derived data can address theoretical questions, noting that they occasionally modify the questions to conform to the limitations of the methods, while at the same time ensuring that the models remain relevant to microbial systems, another important challenge.
From page 31...
... Zhou cautioned that it is misleading to equate the abundance of data that can be derived from a given sample with the actual quantity of samples. "We don't have enough data, far away from enough, to ask ecological questions," he said, giving the example of time series dynamics, which requires a minimum of 40 to 100 time points, "but it's experimental, we don't have this kind of flexibility; this is also a very big issue." Even given an abundance of data, Vega Thurber noted that it is often difficult to parse the directionality of the response, "Is the microbiome directly influencing the host?
From page 32...
... Constrain it in some way." Discher and McFall-Ngai suggested that the cohort of URoL microbiome researchers consider establishing "Rules of Life standards" to help validate data sets. McFall-Ngai described one way such an effort could push the science forward.
From page 33...
... Vega Thurber suggested holding more frequent meetings for URoL researchers, which "would be really utilitarian and helpful for everyone." SOCIETAL IMPACT AND SIGNIFICANCE OF WORK Handelsman noted "so many connections here … to important questions and advances that we could make for society." Some of these connections were mentioned during the meeting. Addressing the Impacts of Climate Change on the Environment and Human Health Benthic toxic cyanobacterial blooms constitute an emerging and widespread environmental problem, said Christova.
From page 34...
... A PI who was unable to attend the workshop wrote that "bacterial communities produce significant N2O and CO2," and that their URoL-funded work "suggests ways to engineer communities to control these emissions" and thereby ameliorate their contribution to climate change. Increasing the Food Supply Understanding how the fish gut microbiome contributes to digestion will allow for its manipulation in aquaculture settings to optimize fish growth, fish health, and food quality while reducing costs, said Allen.
From page 35...
... alters biological networks in ways that may modify success of the restoration process." Another project "will provide key insights into cnidarian biology, which is urgently needed for the design and implementation of global preservation efforts." Stating this more generally, this last respondent wrote that "understanding the function of microbiota in complex systems might aid in the rescue of threatened ecosystems like coral reefs." EDUCATION AND TRAINING Participants discussed their strategies for training a future generation of researchers who can tackle complex scientific problems from a multidisciplinary perspective. Several participants noted the importance of training students in teams led by experts from multiple fields.
From page 36...
... and microbiome ecology, Vega Thurber remarked that the NSF long-term ecological research (LTER) program contained some "beautiful" work along these lines, particularly in forests and soil systems, and that a lot of research is being codeveloped to engage tribal communities and elders to incorporate TEK in microbiome research.


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