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Timetable (UMCW04)

Engineering and Control of Natural and Synthetic Microbial Communities

Wednesday 26th November 2014 to Friday 28th November 2014

Wednesday 26th November 2014
11:00 to 12:15 Registration
12:30 to 13:20 Lunch at Wolfson Court
13:20 to 13:30 Welcome from John Toland (INI Director)
13:30 to 14:05 H Wang (Columbia University)
Plenary Lecture 1: Engineering syntrophic exchange in synthetic microbial communities
Co-authors: Michael T. Mee (Boston University), James J. Collins (Boston University), George M. Church (Harvard Medical School)

Metabolic crossfeeding is an important process that can broadly shape microbial communities. However, little is known about specific crossfeeding principles that drive the formation and maintenance of individuals within a mixed population. Here, we describe the construction of a series of synthetic syntrophic communities to probe the complex interactions underlying metabolic exchange of amino acids. We experimentally analyzed multimember, multidimensional communities of Escherichia coli of increasing sophistication to assess the outcomes of synergistic crossfeeding. We find that biosynthetically costly amino acids including methionine, lysine, isoleucine, arginine, and aromatics, tend to promote stronger cooperative interactions than amino acids that are cheaper to produce. Furthermore, cells that share common intermediates along branching pathways yielded more synergistic growth, but exhibited many instances of both positive and negative epistasis when these interactions sca led to higher dimensions. In more complex communities, we find certain members exhibiting keystone species-like behavior that drastically impact the community dynamics. Based on comparative genomic analysis of >6,000 sequenced bacteria from diverse environments, we present evidence suggesting that amino acid biosynthesis has been broadly optimized to reduce individual metabolic burden in favor of enhanced crossfeeding to support synergistic growth across the biosphere. These results improve our basic understanding of microbial syntrophy while also highlighting the utility and limitations of current modeling approaches to describe the dynamic complexities underlying microbial ecosystems. This work sets the foundation for future endeavors to resolve key questions in microbial ecology and evolution, and presents a platform to develop better and more robust engineered synthetic communities for industrial biotechnology.

Related links: http://wanglab.c2b2.columbia.edu/ - Wang Lab at Columbia University
INI 1
14:05 to 14:40 K Foster (University of Oxford)
Plenary Lecture 2: Cooperation and competition in microbial communities
Since Darwin, evolutionary biologists have been fascinated by cooperative behavior. Honeybee workers labor their whole life without reproducing, birds make alarm calls, and humans often help one another. One major group that remains relatively unexplored, however, is the microbes whose full spectrum of sociality only recently came to light. Microbes often live in large dense groups where one cell can strongly affect the survival and reproduction of others. But do microbes typically help or harm those around them? We study this question using a diversity of systems, including computer simulations, pseudomonad bacteria and budding yeast. We find that single-genotype patches naturally emerge in microbial groups, which creates favorable conditions for cooperation within a particular genotype. Moreover, some microbes actively adjust both genotypic assortment and investment into social traits in a way that promotes cooperation within a genotype. However, our work on interactions be tween different microbial genotypes suggests that, here, the evolution of competitive phenotypes is more likely than cooperation. This leads us to a simple model – the genotypic view – that predicts microbes will evolve to help their own genotype but harm most other strains and species that they meet. We are now moving to understand how our understanding of cooperation and competition in microbial communities can contribute to design principles associated with synthetic and natural systems.
INI 1
14:40 to 15:15 W Shou (FHCRC)
Plenary Lecture 3: tba
INI 1
15:15 to 15:45 Afternoon Tea
15:45 to 16:20 E Trably (INRA - Institut National de la Recherche Agronomique)
Plenary Lecture 4: tba
INI 1
16:20 to 16:55 B Smets (Technical University of Denmark)
Plenary Lecture 5: Engineering microbial community architecture to set community metabolism
The composition of a microbial community is a major indicator of a community’s metabolic potential. However, the spatial structure of that community, imposed or inherently present, can dictate its extant activity. We are keen to explore how we can steer the spatial structure of open and synthetic microbial communities to select or stabilize a target community metabolism from its constituent members. I will provide experimental and computational insights in our efforts to engineer spatially structured communities to generate redox-stratified biofilms for autotrophic nitrogen removal. These communities can provide test grounds for ecological enquiries and building blocks for technological applications.
INI 1
16:55 to 17:10 O Croze (University of Cambridge)
Contributed Talk 1: tba
INI 1
17:10 to 18:00 Welcome Wine Reception and Poster Session INI 1
Thursday 27th November 2014
09:30 to 10:05 V de Lorenzo ([Centro Nacional de Biotecnología])
Plenary Lecture 6: Metabolic conflicts drive multi-scale organization of microbial activities
Biological bottlenecks for microbial biodegradation of recalcitrant compounds in the environment include [i] unfavourable thermodynamics of (bio)chemical reactions at stake, [ii] lack of specificity of existing pathways and enzymes for novel substrates, and [iii] physicochemical stress encountered in polluted sites. Besides these limitations, bacterial cells also experience increased endogenous oxidative stress during metabolism of aromatic compounds, which is exacerbated when enzymes meet suboptimal substrates. Evolving bacterial metabolism is thus shaped by chemical constraints acting on the material and dynamic layout of enzymatic networks -and beyond. These are moulded not only for optimisation of given metabolic objectives (e.g. synthesis of a particular amino acid or nucleotide) but also for curbing the detrimental reactivity of chemical intermediates. These features suggest that the physical structure of existing biosystems, from operon assemblies to multi-cellular development may ultimately stem from the need to restrain chemical damage and limit the waste inherent to basic metabolic functions. We have examined oxidative stress brought about by the still-evolving 2,4-dinitrotoluene biodegradative pathway in Burkholderia sp. DNT. The dnt pathway of this bacterium apparently evolved from a precursor naphthalene degradation route and the first enzyme (2,4-dinitrotoluene dioxygenase) maintains some activity towards its earlier substrate. Examination of both in vivo reactions and the associated regulatory system suggests that ROS production is the first bottleneck that evolving pathways have to overcome for dealing with novel compounds. Evolutionary consequences -and some hints and genetic tools for engineering multi-strain biocatalysts- will be discussed.
INI 1
10:05 to 10:40 J van der Meer (Université de Lausanne)
Plenary Lecture 7: tba
INI 1
10:40 to 10:55 JF Poyatos (Consejo Superior de Investigaciones Cientificas)
Contributed Talk 2: tba
INI 1
10:55 to 11:25 Morning Coffee
11:25 to 11:55 A Pinto (University of Glasgow)
Plenary Lecture 8: tba
Since Darwin, evolutionary biologists have been fascinated by cooperative behavior. Honeybee workers labor their whole life without reproducing, birds make alarm calls, and humans often help one another. One major group that remains relatively unexplored, however, is the microbes whose full spectrum of sociality only recently came to light. Microbes often live in large dense groups where one cell can strongly affect the survival and reproduction of others. But do microbes typically help or harm those around them? We study this question using a diversity of systems, including computer simulations, pseudomonad bacteria and budding yeast. We find that single-genotype patches naturally emerge in microbial groups, which creates favorable conditions for cooperation within a particular genotype. Moreover, some microbes actively adjust both genotypic assortment and investment into social traits in a way that promotes cooperation within a genotype. However, our work on interactions be tween different microbial genotypes suggests that, here, the evolution of competitive phenotypes is more likely than cooperation. This leads us to a simple model – the genotypic view – that predicts microbes will evolve to help their own genotype but harm most other strains and species that they meet. We are now moving to understand how our understanding of cooperation and competition in microbial communities can contribute to design principles associated with synthetic and natural systems.
INI 1
11:55 to 12:30 C Picioreanu (Delft University of Technology)
Plenary Lecture 9: tba
INI 1
12:30 to 13:30 Lunch at Wolfson Court
14:00 to 14:35 M Asally (University of California, San Diego)
Plenary Lecture 10: tba
INI 1
14:35 to 15:10 M Barer (University of Leicester)
Plenary Lecture 11: tba
INI 1
15:10 to 15:25 Contributed Talk 3: tba INI 1
15:25 to 15:55 Afternoon Tea
15:55 to 16:30 J Prosser (University of Aberdeen)
Plenary Lecture 12: tba
INI 1
16:30 to 17:05 A Free (University of Edinburgh)
Plenary Lecture 13: Unpredictability in Microbial Communities and How to Deal With It
Co-authors: Eulyn Pagaling (University of Edinburgh), Fiona Strathdee (University of Edinburgh), Kristin Vassileva (University of Edinburgh), Rocky Kindt (University of Edinburgh), Rosalind J. Allen (University of Edinburgh)

The ability to control and engineer complex microbial communities for particular purposes or functions depends on the reproducibility and stability of community structure and function under controlled conditions. Natural microbial communities contain many low-abundance species, comprising the so-called “rare biosphere”, which may be selected when the environmental parameters governing the system are altered. Current data suggest that the stochastic selection of rare species, together with the complex, non-linear dynamics of these communities, can lead to unpredictability of community structure and function following environmental selection.

We investigate this phenomenon using a simple, replicable laboratory model system, or microcosm, containing diverse microbial ecotypes which cycle nutrients such as carbon and sulphur compounds and generate community function in the form of a redox potential gradient. Variability in the microbial community composition of this model system, studied by 16S rRNA gene-based fingerprinting and sequencing methods, is observed following a selective bottleneck in the system caused by anaerobiosis. Concomitant variation in the development of the redox gradient is also seen. However, stable final communities from this system re-inoculated into the same environment exhibit much less variability than the original communities and a final organisational state which is closely related to their initial state at inoculation. These results suggest that selection under novel environmental conditions can cause unpredictability in microbial community structure and function, but that repeated sele ction can be a means to ensure predictability. We discuss these phenomena with reference to microbial photobioreactor systems containing low microbial diversity which are amenable to engineering by “synthetic ecology”.
INI 1
17:05 to 17:20 Contributed Talk 4: tba INI 1
17:20 to 17:35 Contributed Talk 5: tba INI 1
19:30 to 22:00 Conference Dinner at Cambridge Union Society hosted by Cambridge Dining Co.
Friday 28th November 2014
09:30 to 10:05 P Wilmes ([University of Luxembourg])
Plenary Lecture 14: Ecosystems Biology: from data to control of microbial communities
Co-authors: Emilie Muller (University of Luxembourg), Anna Heintz-Buschart (University of Luxembourg), Shaman Narayanasamy (University of Luxembourg), Cédric Laczny (University of Luxembourg)

Mixed microbial communities are complex and dynamic systems. Integrated omics (combined metagenomics, metatranscriptomics, metaproteomics and metabolomics) are currently gaining momentum for detailed descriptions of community structure, function and dynamics in situ as well as offering the potential to discover novel functionalities within the framework of Eco-Systems Biology. We have developed an integrative workflow comprising wet- and dry-lab methodologies to enable systematic measurements of microbial communities over space and time, and the integration and analysis of the resulting “multi-meta-omic” data. Two distinct approaches have been developed allowing the deconvolution of integrated omic data either at the population- or community-level. By resolving multi-omic data at the population-level, we have uncovered patterns which suggest that in our model microbial community (lipid accumulating microbial consortia from a biological wastewater treatment tank) t he dominance of a microbial generalist is linked to finely tuned resource usage. Analysis of reconstructed metabolic networks has resulted in the identification of possible “keystone genes”, analogous to keystone species in species interaction networks. Integrated omics will likely become the future standard for the large-scale characterization of microbial consortia within an Eco-Systems Biology framework. In particular, by integrating information from genome to metabolome, integrated omics allows deconvoluton of structure-function relationships by identifying key members and functionalities. For example, identified keystone species and/or genes likely represent driver nodes which may be exploited in view of future control strategies. However, to test emerging hypotheses and formulate predictive models, which support such endeavours, an iterative discovery-driven planning approach is required. This should ultimately allow the manipulation of microbial communities and steer them towards desired outcomes.

INI 1
10:05 to 10:40 J Rodriguez (Masdar Institute of Science and Technology)
Plenary Lecture 15: tba
INI 1
10:40 to 10:55 Contributed Talk 6: tba INI 1
10:55 to 11:25 Morning Coffee
11:25 to 11:55 Plenary Lecture 16: tba INI 1
11:55 to 12:30 Plenary Lecture 17: tba INI 1
12:30 to 13:30 Lunch at Wolfson Court
University of Cambridge Research Councils UK
    Clay Mathematics Institute The Leverhulme Trust London Mathematical Society Microsoft Research NM Rothschild and Sons