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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 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: - Wang Lab at Columbia University
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.
14:40 to 15:15 Plenary Lecture 3: Bacterial interactions in synthetic communities and in the wild
Predicting how bacterial community structure impacts ecosystem functioning requires quantifying how bacteria interact in natural environments. Our past research has used synthetic communities to characterise the ecology and evolution of bacterial interactions. Results indicate that: (i) interactions tend to be antagonistic, (ii) community complexity mollifies antagonisms and favours positive interactions, (iii) interactions evolve rapidly with repercussions for ecosystem functioning, and (iv) higher-order interactions are relatively unimportant. However, extrapolating these results to natural environments is challenging because of the complexity these communities. I will discuss one potential solution, which uses common garden experiments to quantify interactions in complex communities collected from nature.
15:15 to 15:45 Afternoon Tea
15:45 to 16:20 Plenary Lecture 4: Eco-engineering of fermentative microbial communities: the role of keystone species

Microbial mixed cultures present a broad metabolic flexibility and allow considering complex organic biomass as potential resources for biomolecules and hydrogen production in dark fermentation processes. A wide number of microbial species are able to ferment carbohydrates, but a high microbial diversity is often detrimental to bioprocess operation since it leads to process instability. To date, only few controllers, essentially physicochemical, are available to control finely the multiplicity of bacterial metabolisms in mixed cultures. And no strong or very specific selection pressure could be applied to enrich in efficient and robust microbial communities. One possibility would be to engineer ecologically these communities to better control the metabolic networking. For that, we investigated the use of keystone species as biotic triggers of the fermentative metabolism in mixed cultures. First some keystone species, often low in abundance but having a major role on metabolic networks, were identified from several natural ecosystems. Different strategies of biotic control of the fermentative microbial communities were then investigated, confirming the important role of these species and the possibility of using them as biotic controllers of the overall community. Artificial co-cultures were also carried out, and a specific type of interaction was characterized. Beyond this study, it is expected that these findings lead to new biotechnological or environmental applications through the use of biotic control of microbial metabolisms.

16:20 to 16:55 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.
16:55 to 17:10 JF Poyatos (Consejo Superior de Investigaciones Cientificas)
Contributed Talk 1: Synthetic microbial systems as ecosystems simulators
Co-authors: Clara Moreno (CNB-CSIC), Matteo Cavaliere (CNB-CSIC), Esteban Martinez-Garcia (CNB-CSIC)

An ideal ecosystem “simulator” would permit the study of ecological questions that are difficult to analyze in the field, and whose details are sometimes not easy to incorporate by means of ab initio computer models. Here, I propose the use of synthetic bacterial systems as such “simulators” by discussing one case study. This is focused on the issue of how certain stressors impact ecosystems that rest on public resources, a fundamental question for risk assessment. We will thus engineer a community that relies on public goods to manage stress. With this “simulator”, I will try to show how the availability of essential resources, and the presence of habitat heterogeneities eventually influence the effect of the stressor. Some surprises are guaranteed.

17:10 to 18:00 Welcome Wine Reception and Poster Session INI 1
Thursday 27th November 2014
09:30 to 10:05 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.
10:05 to 10:40 Plenary Lecture 7: Lignocellulose degradation by enriched microbial consortia from cow rumen and termite gut
Co-authors: Lucas Auer (idem), Adèle Lazuca (idem), Maider Abadie (idem), Gunnar Oelker (idem)

Bioconversion of lignocellulosic biomass into energy and synthons of industrial interest is of current concern to reduce the fossil energy dependence. Lignocellulose can be converted into carboxylates which can be used to produce added-value products (e.g biofuels or bioplastics). Such transformation can be realized by microbial consortia issued from the digestive tract ruminants and phytophage insects. Our aim was to produce microbial consortia displaying stable microbial diversity, high lignocellulolytic potential and high capacity to produce carboxylates using termite gut and cow rumen microbiomes. We also wanted to correlate the functional diversity of these consortia with their enzymatic activity and lignocellulose degradation profiles. To this aim, we studied the lignocellulolytic capacities of cow rumen and gut microbiomes of four species of tropical termites (Termes hospes, Microcerotermes parvus, Nasutitermes lujae and N. ephratae). Lignocellulose transformation was tested in anaerobic reactors (35°C) using wheat straw as sole carbon source. Carboxylate production and residual lignocellulosic substrate were regularly monitored during the incubation period (15 d). Our data showed that gut microbiomes from N. ephratae displayed high capacities to degrade lignocellulose. N. ephratae cow rumen microbiomes were selected to enrich the most active lignocellulolytic spe cies by sequencing batch reactor process. After 10-12 cycles, stable consortia were obtained. Sequencing of 16S rRNA gene showed important differences in the functional species present in these ecosystems compared to the initial communities. The enzymatic activities (endoglucanase, ß-glucosidase, xylanase, ß-xylosidase), mainly associated to the cell biomass, suggested the production of cellulosome-like systems. In this presentation, insights in enzymes activities and diversity will be discussed, providing better understanding of lignocellulose deconstruction by microbial consortia.

10:40 to 10:55 Contributed Talk 2: Long distance relationships between algae and bacteria
Co-authors: F. Peaudecerf (Department of Applied Mathematics and Theoretical Physics (DAMTP), University of Cambridge), M. A. Bees (Department of Mathematics, University of York), R. E. Goldstein (Department of Applied Mathematics and Theoretical Physics (DAMTP), University of Cambridge), A. G. Smith (Department of Plant Sciences, University of Cambridge)

Microbial interactions are often predicated on metabolism: e.g. auxotrophs depend on nutrients made by other microbes. Many algae are vitamin auxotrophs, with several known species requiring exogenous vitamin B12 [1]. This vitamin must be obtained from bacteria, as only they can synthesise it. Laboratory experiments have demonstrated mutualistic interactions between bacteria and B12-dependent algae. Populations of the bacterium Mesorhizobium loti (B12 producer, carbon requirer) and the green alga Lobomonas rostrata (B12 requirer, carbon producer) in co-culture stabilise to an algae/bacteria ratio of 1/30, independent of initial inoculum ratio [2]. system [3].

Here we consider the interactions between microbial populations separated in space. Experiments on hard agarose indicate that mutualistic interactions exist at a distance. We present a mathematical model capturing the essence of these experiments: growing populations of algae and bacteria coupled by a diffusive channel. Solutions to the model reveal rich dynamics. We will discuss these and speculate on the ecological significance of our findings for understanding environmental biofilms and microbial mats.

[1] Croft, M. T. et al. Nature 483:90–93 (2005) [2] Kazamia, E. et al. Environ. Microbiol. 14, 1466 (2012)

10:55 to 11:25 Morning Coffee
11:25 to 11:55 Plenary Lecture 8: Towards a predictive framework for microbial community dynamics in drinking water systems
The abundant and diverse drinking water microbiome migrates daily from the drinking water treatment plant through the distribution systems into our homes, offices, schools, etc. Every litre of water emerging from our taps has tens of millions of microbes – bacteria, archaea, eukaryotes, and viruses – all of which constitute a complex microbial community. Effectively managing this diverse microbial community is not only critical from a public health perspective, but also has implications for our water infrastructure (e.g. microbially mediated corrosion). Efforts to manage the drinking water microbiome would be well served by a framework that can predict its dynamics as a function of process operations, environmental conditions, and water supply infrastructure over relevant spatial and temporal scales. A predictive framework would pave the way for a nuanced control of the drinking water microbiome, which will save labour, energy and may also ultimately promote heal th. This presentation will outline efforts to develop a such predictive framework for water systems in the US and Europe.
11:55 to 12:30 N Krasnogor (Newcastle University)
Plenary Lecture 9: Computation and Polymer Synthesis for Designer Quorum Sensing Behaviour
Bacteria deploy a range of chemistries to regulate their behaviour and respond to their environment. Quorum sensing is one method by which bacteria use chemical reactions to modulate pre-infection behaviour such as surface attachment. A combination of polymer and analytical chemistry, biological assays and computational modelling has been used to characterize the feedback between bacteria clustering and quorum sensing signalling. We have also derived design principles and chemical strategies for controlling bacterial behaviour at the population level. In this talk I will summarise our work on the utilisation of computational modelling for the design of synthetic polymers affecting QS phenotypes and, , time permitting, the combinatorial DNA library design tool (DNALD).
12:30 to 13:30 Lunch at Wolfson Court
14:00 to 14:35 Plenary Lecture 10: tba INI 1
14:35 to 15:10 M Barer (University of Leicester)
Plenary Lecture 11: The good the bad and the irrelevant. Sequential analyses of the sputum microbiome in patients with Chronic Obstructive Pulmonary Disease
Co-authors: Koirobi Haldar (University of Leiceister), Mona Bafadhel (University of Oxford), Chris Brightling (University of Leiceister)

COPD is a chronic respiratory disease associated with progressive deterioration of lung function and eventually death from respiratory failure; chronic exposure to smoke is the major aetiological risk factor and the disease is a major WHO priority. COPD patients have excess production of mucus in their lower airways and this is coughed up as sputum which supports an abundant and diverse microbiome. The course of the disease is characterised by exacerbations in which cough and sputum production increase and lung function worsens. The causes of COPD exacerbations are hotly debated and are likely to be multiple. The view that infections, attributable to one or more microbial pathogen, are the primary cause of exacerbations is widely accepted by physicians and sanctioned by the almost universal use of antibiotics. However, rigorous evidence in support of this view is lacking. We have conducted the first sequential study of the sputum microbiome in COPD patients with samples taken when stable, at the time of exacerbation (prior to antibiotics) then 2 and six weeks later, when all had recovered from the episode. Microbiome profiling was based on Roche 454 sequencing of 16S-rDNA amplicons. With the exception of a small group of virus positive exacerbations the events could not be explained by the arrival or increased abundance of recognised pathogens. Microbiome analyses revealed a high frequency of 20 different phyla in most samples but consistent dominance of Proteobacteria and Firmicutes. No clear pattern with respect to composition or diversity of the microbiome was associated with exacerbations. However, cluster analysis revealed a subgroup of exacerbations in which disturbance of the ratio between Proteobacteria and Firmicutes occurred and subsequently returned to the stable value following therapy. We propose that this subgroup may be patients who need antibiotics while they are unnecessary or even harmful for patients whose microbiomes did not show this pattern.

15:10 to 15:25 Contributed Talk 3: Flux analysis in microbial ecosystems
Environmental bioprocess modeling has proven as a very useful tool for analysis of natural and man-made ecosystems. Attributing specific redox reactions to specific microbial groups allows for investigating a complex microbial community as the sum of the different reactions in the system. Inclusion of the microbial redox reactions in bioreactor systems and by including thermodynamic equilibria, phase transfer reactions, and spatial distribution of reactions allows for establishment of an overall system description. This kind of models have been used for analysis of numerous wastewater treatment related processes like the activated sludge process, anaerobic digestion, and biofilm processes. In recent years metaproteogenomic methods have become available to investigate microbial ecosystems. To which extent these methods and the corresponding modeling tools are of interest for research in the field of applied environmental microbiology will be the topic of this presentation. First I will present an overview of recent modeling efforts in our research group, and based on that experience I will discuss the potential role of metaproteogenomic tools in the field of environmental microbiology.
15:25 to 15:55 Afternoon Tea
15:55 to 16:30 J Prosser (University of Aberdeen)
Plenary Lecture 12: The paradox of nitrification in acid soils and lessons for microbial community ecology
Co-author: Cecile Gubry-Rangin (University of Aberdeen)

A major, long-standing question in nitrifier ecology has been the paradox of nitrification in acid soils: cultivated ammonia oxidisers cannot growth in liquid batch culture below pH 7 but gross nitrification rate in soil is unaffected by pH and some of the highest rates are seen in soils of pH 4 – 5. This question is of both scientific interest and significant global economic importance, as approximately 30% of the world’s soils are acidic, including 50% of arable soils, and up to 70% of ammonia-based nitrogen fertiliser is lost through nitrification and leaching or denitrification of nitrate. Although several mechanisms were proposed for growth of bacterial ammonia oxidisers in acid soils, a major breakthrough was evidence that the ratio of archaeal:bacterial amoA genes and gene transcripts increase as pH decreases, suggesting that acidophilic archaeal ammonia oxidisers may exist. Further evidence for this hypothesis was a global study of the distribution of archaeal amoA genes, which indicated that pH was a major factor determining archaeal ammonia oxidiser distribution in soil and identifying clusters associated with soils of different pH. The pH preference for these clusters was confirmed by predictions of their distribution in a large number of UK soil covering a range of pH values. The second line of evidence was the isolation of an acidophilic archaeal ammonia oxidisers, Nitrosotalea devanaterra, which belongs to one of the acidophilic clusters characterised in the global study, and demonstration of its growth in acid soil. While discussing this specific question in ammonia oxidiser community ecology, the different approaches used will be discussed and compared and will be used to exemplify the current state of microbial community ecology and ways in which new technologies may help and hinder future studies.

16:30 to 17:05 Plenary Lecture 13: Variability and Alternative Community States in Microbial Communities
Co-authors: Eulyn Pagaling1,2*, Katsiaryna Usachova1,3, Liudmila Usachova4, Fiona Strathdee1, Kristin Vassileva1, Rocky Kindt1, Rosalind J. Allen2

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. This can also result in alternative stable states of the system which may be difficult to interconvert.

We give an example of a wastewater treatment plant processing urban waste streams, describing the operational problems caused by the emergence of stable undesirable community states and challenges in recovering the diversity, structure and function. We then investigate the phenomena of alternative states and unpredictability using a simple, replicable laboratory model system (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 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 microcosm communities 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 selection 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".

17:05 to 17:20 M Ortiz (Harvard University)
Contributed Talk 4: Optimization-based tools for bacterial ecology design
Bacteriophage-based cell-cell communication allows users to create genetically dynamic bacterial ecologies by transmitting DNA molecules between E. coli cells. In previous work, I demonstrated how such a system could be used to transmit DNA messages having different functionalities to develop ecologies over hours-long time courses in liquid or over solid media. If well-designed, such ecologies have the ability to compute, amplify, or report state as a population.

One immediate problem encountered in designing stable bacterial ecologies is that relatively small differences in individual growth rates can impact the resulting population mix in little time. As such, we have focused on developing optimization-based tools for relating the initial and final states of heterogeneous baterial ecologies. We have created a scalable model of the phage-based communication platform to aid development of more complex engineered bacterial ecologies. By inputting few experimental parameters as well as an arbitrary desired output behavior, users can easily obtain the necessary inputs to their engineered system. As phage-based communication via DNA transmission inherently creates genetically distinct species as phage infection proceeds, this tool also enables the user to design and optimize for time-varying behaviors. Overall, it is hoped that such tools will enable greater complexity of heterogeneous bacterial mixtures, help us better understand ec ologies, and allow us to narrow the gap between natural and synthetic systems.

17:20 to 17:35 Contributed Talk 5: Numerical Continuation of Equilibria of Cell Population Models with Internal Cell Cycle
I will discuss the behavior of a model describing unicellular organisms living in a continuous culture. We do this mainly numerically, with the help of an extended version of bifurcation analysis adapted to this type of quite complex (structured) population dynamics. The complexity is induced by attaching a whole physiological structure to each of these cells, which in the present case describes the states of their internal cell cycle. Other pathways based on biochemistry would entirely fit into the modeling framework as well. In our example the cycling speed through the cell cycle will depend on the environment, which in a bioreactor environment is just the concentration of some limiting nutrient in the main tank where microbial growth takes place. The model serves well as a basis of multi-scale mathematical modeling of microbial activity, from internal cell biochemistry up to the population level, like distributions of microbial biomasses in the environment. Howev er, medical applications can be covered as well.
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 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.

10:05 to 10:40 Plenary Lecture 15: Can bioenergetics tell us more about microbial ecosystems activity than community identity?
Co-authors: Rebeca González-Cabaleiro (University of Santiago de Compostela (ES)), Robbert Kleerebezem (Delft University of Technology (NL)), Juan M. Lema (University of Santiago de Compostela (ES))

Bioenergetic considerations appear to play a central role in defining microbial ecosystems activity irrespective of the microbial community identity. Our modelling results suggest that mainly bioenergetics can define the activity of microbial ecosystems at three different levels: (1) When a generalized bioenergy-based model is used to describe the competition between a number of existing and postulated microbial metabolisms, the prevailing successful ones, the reasons behind their success and some syntrophisms are correctly predicted. This has been applied to glucose fermentation and to nitrogen oxidation and reduction ecosystems. Metabolic activities appear to be selected by maximum energy harvest rate. Based on this we postulate that it is primarily energetics who defined the today existing microbial metabolisms, pathway lengths and synergisms among them. (2) When specific anaerobic fermentative reactions of interest are studied under a thermodynamic perspective, conclusions can be drawn out about their potential reversibility. Quasi equilibrium calculations can be used to estimate concentration limits for the feasibility of pathway steps and compares with physiological and kinetic limits. Based on this we postulate that in energy limited microbial ecosystems, thermodynamic limitations can impose unfeasible intermediate metabolite concentrations rendering a metabolic pathway impossible or reversing it. (3) When anaerobic fermentation microbial ecosystems are described as one mass and electron balanced metabolic network, an optimisation of the network for maximum energy yield can provide an accurate prediction of the product formation. This has been successfully applied to the prediction of products and their shifts as a function of the environmental pH. Based on this we postulate that in energy limited microbial ecosystems such as fermentations, a bioenergetic maximum energy harvest rate criteria defines the product spectrum irrespective of the microbial community.

10:40 to 11:25 Morning Coffee
11:25 to 11:55 L Raskin (University of Michigan)
Plenary Lecture 16: Managing microbial communities in anaerobic membrane bioreactors
Anaerobic membrane bioreactor (AnMBR) systems have recently come to the forefront as promising options for mainstream anaerobic treatment of domestic wastewater. Our research has demonstrated with a bench-scale AnMBR that this technology can produce effluent quality comparable to activated sludge treatment at temperatures as low as 6°C. However, we have also demonstrated that this technology can only become competitive as an alternative domestic wastewater treatment option after addressing its high global warming potential due to the presence of dissolved methane in the permeate and the high energy demand for fouling control. While these appear to be typical process engineering problems, we contend that management of the complex anaerobic microbial communities in AnMBR is an essential component of solving these challenges and will show experimental data in support of this statement.
11:55 to 12:30 Plenary Lecture 17: Modeling biofilm formation in porous media and fouling in membrane processes
Biofilm formation in porous media is determined by a multitude of processes not only different in nature, but also in spatial and temporal scales, making in general the whole system challenging to study. This presentation will introduce concepts and approaches to biofilm modeling at pore scale. We couple two- or three-dimensional fluid dynamics models with solute transport supplying nutrients for biofilm development in complex geometry media. The biofilm formation can be described by particle-based models, with growth dependent of nutrient concentrations and detachment as a function of shear stress induced by flow. Mineral precipitation can also be introduced in the particle-based framework. A first application evaluates the impact of biofilms on proppant packed fractures in shale gas reservoirs. Simulations of two-phase flow indicated that although hydrophobic proppant grains provide better dewatering than hydrophilic surfaces, biofilms can worsen the dewatering. Model extensions show how biofilm lysis can create flow paths continuously changing position even after the medium permeability reached steady state. The second series of examples describes the effect of biofilm growth in spacer-filled channels of reverse osmosis membrane devices for water desalination. The 3-d numerical simulations show how biofilm accumulation strongly affects the feed channel pressure drop and liquid channeling. Furthermore, accumulation of salts near the membrane and mineral precipitation is stimulated by the biofilm. The micro-scale models can explain experimental observations on particle deposition patterns, biofilm and crystal formation.
12:30 to 13:30 Lunch at Wolfson Court
University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons