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Timetable (UMCW01)

Interdisciplinary Approaches to Understanding Microbial Communities

Wednesday 10th September 2014 to Friday 12th September 2014

Wednesday 10th September 2014
11:00 to 12:30 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: Contingency and convergence in microbial population dynamics
I will present some results of long-term laboratory experiments in closed microbial ecosystems. Each system is a small world in itself, with its idiosyncrasies and (hi)story to tell. Local population dynamics is monitored in dozens of replicates. Surprisingly, statistical laws governing the population fluctuations seem to be quite simple. But then, even more controlled experiments are performed...
14:05 to 14:40 S Frank (University of California, Irvine)
Plenary Lecture 2: Cancer-like overgrowths and genomic regulatory design in microbes
Mutant lineages may cause cancer-like overgrowths in microbial populations. Theory predicts that microbial regulatory controls may be designed to limit the origin and competitive potential of rogue lineages. The theory depends on the fundamental tradeoff between rate and yield in microbial metabolism. The rate versus yield tradeoff and the role of cancer-like overgrowths are influenced by the genetic structure of populations and by demographic processes such as how long resource patches last.
14:40 to 15:15 T Curtis (Newcastle University)
Plenary Lecture 3: Simple Theory and the Microbial World
Co-authors: Bill Sloan (Glasgow University), Dana Ofiteru (Newcastle University), Lise Ovreas (Bergen University), Joana Baptista (Newcastle University), Chris Quince (Glasgow University)

The microbial world is of astronomical dimensions and of profound practical importance. And yet, though astronomers and engineers rely heavily on quantitative theory, most microbial ecologists and associated practitioners do not. Those that do, are heavily influenced by classical ecological theory. However, most classical ecological theory is not “up to the job”. The inscrutability and practical importance of the microbial world means that prediction should be our aspiration. This imposes certain disciplines up on us. In particular, we should start as simply as possible, find and understand the parameters and what they can explain; and then move on. The simplest possible theory of community assembly in microbial communities is perhaps the work of Bill Sloan and his colleagues. The key parameters are the size of the community, the immigration rate and the size and make up of the metacommunity. The size of the community we often know. Finding the immigration par ameter yields useful insights about how communities form and change and the relative importance of immigration and evolution. The size and the nature of the metacommunity is less well understood, but its exploration hints at generic and useful rules in evolution that could be both intrinsically interesting and very important. However, we should look forward to a future in which mathematics has the stature and utility in microbial ecology, that it enjoys in physics. Then microbial ecology will done at the scale and with the rigour that the field merits.

15:15 to 15:45 Afternoon Tea
15:45 to 16:20 Plenary Lecture 4: Phage and Origins of the Immune System
Immune responses and mucosal surfaces of corals and humans are strikingly similar despite greater than 500 million years of divergence. Here we show that humans and phage both use bacteriophage to protect against bacteria and establish microbiomes. This Bacteriophage Adherence to Mucus (BAM) model is applicable to all metazoans. The model links hypervariable phage capsid decoration proteins with the adherence of phage to mucus and it's consequent reduced bacterial pathogenesis of underlying host epithelium. The relationships delineated make the world's most abundant biological entities central to the metazoan immune system. In so doing, they advance our understanding of immunology and the microbial ecology of a key metazoan-associated environments, and will open new directions in immunological engineering.
16:20 to 16:55 T Rogers (University of Bath)
Plenary Lecture 5: Survival of the unfit - how demographic noise can create suboptimal species
Co-author: Alan J McKane (University of Manchester)

Competition between individuals drives the evolution of whole species. When the fittest individuals survive the longest and produce the most offspring, it is conventionally assumed that the resulting species will therefore also be optimally fit. In fact, this reasoning is not always correct. Using theoretical analysis and stochastic simulations of a simple model ecology, we demonstrate how the fitness of evolved populations depends on the detail of the competitive interaction. In particular, if competition is mediated by the consumption of a common resource then demographic noise leads to the stabilisation of species with near minimal fitness.

Related Links: • - Perprint describing the work in detail

16:55 to 17:10 S Kalvala (University of Warwick)
Contributed Talk 1: Computational models of spatial behaviour of microbial communities
Computational simulations are now an important component of the toolkit for studying biological systems. While it is easy to simulate well-mixed solutions in order to model intra-cellular processes, it is more difficult to capture spatial phenomena characterizing microbial communities. The problem is compounded because we need to capture not only inter-cellular communication but also changing configurations, with microbes that move, change shape, and create new communication channels.

In this talk I will review some of the methodologies that have been developed for spatially-aware computational modelling of microbial communities and the limitations of these methodologies. I will also present some of our results in capturing some of the intriguing behaviour of myxobacteria communities (namely rippling and the formation of fruiting bodies) via a spatial simulation based on the Cellular Potts Model.

17:10 to 18:00 Wine Reception and Poster Session
Thursday 11th September 2014
09:30 to 10:05 T Hwa (University of California, San Diego)
Plenary Lecture 6: Mixed and Hierarchical Utilization of Carbon Substrates by Bacteria
Co-authors: Hiroyuki Okano (UC San Diego), Rutger Hermsen (Utrecht University), Conghui You (UC San Diego)

When bacteria are cultured in medium with multiple carbon substrates, some substrate combinations are consumed simultaneously while other combinations are consumed sequentially. Understanding and manipulating the order of carbon utilization is crucial in characterizing trophism in complex ecosystems such as the gut microbiota, and in optimizing synthetic biology applications such as the breakdown of cellulose for biofuel production. Building on recent advances in the understanding of metabolic coordination exhibited by Escherichia coli cells through cAMP-Crp signaling, we show that this signaling system alone gives rise to simultaneous utilization, and derive an algebraic formula describing the resulting growth rate, based only on the growth rates on individual substrates. For substrate combinations that are utilized hierarchically, we reveal a simple regulatory strategy by which the hierarchy is ordered roughly by the rate of growth on single substrates.

10:05 to 10:40 Plenary Lecture 7: Numerical modelling, an interdisciplinary bridge in studying microbial biofilms
Microbial biofilms inherently require multidisciplinary approaches. Numerical models can help the integration of knowledge from various disciplines into unified theories. This presentation will give examples on how mechanical models can be useful computational tools to study pattern formation due to cell motility, spreading of microbial colonies made of mixed cell morphotypes or interactions between fluid flow and biofilms, including streamer vibration effects on flow and mass transfer. Electro-active biofilms (conductive sediments, microbial fuel cells, biocorrosion) require on the other hand bridging other areas of physics and electrochemistry with biology. On the other hand, hydrology and subsurface flow models provide tools for understanding biofilm formation and their effects on multiphase flow in porous media and in biomineralization processes.
10:40 to 10:55 Contributed Talk 2: The Initiative for the Critical Assessment of Metagenome Interpretation (CAMI)
Co-author: Alexander Sczyrba, Eddy Rubin, Nikos Kyrpides, Paul Schulze-Lefert, Julia Vorholt, Nicole Shapiro, Tanja Woyke, Hans-Peter Klenk, Stephan Majda, Johannes Droege, Ivan Gregor, Peter Hofmann, Eik Dahms, Jessika Fiedler, Ruben Garrido-Oter, Yang Bai, Girish Srinivas, Phil Blood, Mihai Pop, Aaron Darling, Matthew DeMaere, Dmitri Turaev, Chris Hill, Peter Belmann, Andreas Bremges, Thomas Rattei ()

In just over a decade, metagenomics has developed into a powerful and productive method in microbiology and microbial ecology. The ability to retrieve and organize bits and pieces of genomic DNA from any natural context has opened a window into the vast universe of uncultivated microbes. Tremendous progress has been made in computational approaches to interpret this sequence data but none can completely recover the complex information encoded in metagenomes.

A number of challenges stand in the way. Simplifying assumptions are needed and lead to strong limitations and potential inaccuracies in practice. Critically, methodological improvements are difficult to gauge due to the lack of a general standard for comparison. Developers face a substantial burden to individually evaluate existing approaches, which consumes time and computational resources, and may introduce unintended biases.

CAMI ( is a new community-led initiative designed to tackle these problems by aiming for an independent, comprehensive and bias-free evaluation of methods. We are making extensive high-quality unpublished metagenomic data sets available for developers to test their short read assembly, binning and taxonomic classification methods. The results of CAMI will provide exhaustive quantitative metrics on tool performance to serve as a guide to users under different scenarios, and to help developers identify promising directions for future work.

As a community effort, we encourage feedback by both method developers and users of metagenome analysis tools. We urge developers to already register for the competition on our website and to join our Google+ group to provide feedback on the current design phase. The competition is tentatively scheduled to open at the end of 2014. The results will be presented and discussed in a workshop after the competition. We aim for a publication of the generated insights together with all CAMI contest participants and data contributors.

10:55 to 11:25 Morning Coffee
11:25 to 11:55 AG Smith (University of Cambridge)
Plenary Lecture 8: Algal-bacterial consortia and evolution of mutualism
Co-authors: Katherine Helliwell (University of Cambridge), Elena Kazamia (University of Cambridge), Matthew Cooper (University of Cambridge), Vaibhav Bhardwaj (University of Cambridge), Christian Ridley (University of Cambridge), Johan Kudahl (University of Cambridge)

Over half of all microalgae require an external source of vitamins, particularly vitamin B12 (cobalamin), to enable them to grow. There is no phylogenetic relationship between those that require the vitamin and those that do not. Bacteria are the only organisms that can synthesise this complex organic micronutrient, and we have shown that B12-dependent algae can grow in co-culture with bacteria that supply them the vitamin in exchange for fixed carbon. We have established a model system to study this interaction at the molecular level, and to explore reasons for why vitamin auxotrophy may have arisen so frequently across the diverse algal lineages. This may provide insights into the evolution of mutualism between algae and their bacterial partners.
11:55 to 12:30 Plenary Lecture 9: Structure and functions of the bacterial phyllosphere microbiota
The aerial parts of the plants, which are dominated by leaves, represent one of the largest terrestrial habitats for microorganisms. This habitat, called the phyllosphere, is occupied by a diverse community of microorganisms, which is important for plant health and growth. Most of the phyllosphere inhabitants are not well investigated; however, there is a growing interest to study commensal bacteria to elucidate their interactions with the plants, among each other and to learn how they withstand the hostile conditions of their habitat. A predominance of Proteobacteria, Actinobacteria and Bacteroidetes living in the phyllosphere of numerous plants has been revealed, while metagenomics and metaproteomics approaches gave insights into the general bacterial adaptation strategies to the phyllosphere. Complementary to these cultivation-independent approaches we established a comprehensive strain collection which covers a broad diversity of strains colonizing the model plant Arabido psis thaliana. Targeted studies with model strains allowed us to identify metabolic traits important for plant colonization and to uncover a novel bacterial regulatory system essential for plant colonization which is responsible for the general stress response in Alphaproteobacteria. The establishment of a gnotobiotic system led to the identification of plant probiotic effects of commensal bacteria and candidate genes for plant protection against bacterial pathogens. Moreover, the experimental system paired with synthetic bacterial communities helped identifying plant genes involved in shaping the bacterial community structure.
12:30 to 13:30 Lunch at Wolfson Court
14:00 to 14:35 H Flint (University of Aberdeen)
Plenary Lecture 10: Phylogeny and functionality in anaerobic microbial communities: making sense of metabolite outputs and population dynamics
Regions of the mammalian gut harbour dense microbial communities that derive most of their energy from the anaerobic breakdown of dietary carbohydrates that are not digested by host enzymes. Especially in herbivores, the organic acids produced by microbial fermentation in turn provide a major supply of energy for the host, while in the human colon they have an important impact on health. It is of key interest therefore to understand how the microbial communities of the rumen and human large intestine respond to dietary change and how this affects the production of alternative metabolic products. While some metabolic and degradative capabilities are widespread among the microbiota, many (eg. methanogenesis, degradation of crystalline cellulose, lactate utilization) appear to be restricted to a small number of phylogenetic groups. Information from cultured isolates, defined consortia, experimental models, metagenomics and in vivo studies is helping to define functional group s of human gut bacteria whose characteristics can be incorporated into theoretical models that explore inter-group interactions and community responses.
14:35 to 15:10 H Kettle (Biomathematics & Statistics Scotland (BioSS))
Plenary Lecture 11: Modelling the emergent dynamics of human colonic microbiota
Co-authors: Petra Louis (University of Aberdeen), Grietje Holtrop (Biomathematics and Statistics Scotland), Sylvia Duncan (University of Aberdeen), Harry Flint (University of Aberdeen )

We present a method for modelling the complex dynamics of the colonic microbial ecosystem that incorporates both the variation in microbial composition between people and ecosystem adaptation. The model is a Monod-equation based, ordinary differential equation model which produces computer simulations of the dynamics of the microbial population and its major metabolites. To reduce the complexity of the system we divide the bacterial community into 10 bacterial functional groups (BFGs) each distinguished by its substrate preferences, metabolic pathways, and its preferred pH range. The model simulates the growth of a large number of bacterial strains with stochastically generated traits which compete for resources. The simulation results are compared with data from four experiments in pH-controlled, anaerobic continuous flow fermentor systems that investigated the effects of pH and peptide supply. We also theoretically investigate the idea that microbial strain diversity may be promoted by a pH feedback mechanism within the colon.
15:10 to 15:25 Contributed Talk 3: A functional population model of fiber degradation by the human intestinal microbiota
Co-authors: Marion LECLERC (MICALIS,INRA), Sebastien RAGUIDEAU (MIA-J, INRA)

The human intestinal microbiota is a complex microbial ecosystem that plays a crucial role in several aspects of human health. It is particularly involved in the metabolism of residual fibres, through anaerobic digestion, thus providing significant energy (Short Chain Fatty Acids, simple sugars) and vitamins to the host. This ecosystem remains largely unexplored as a result of its limited accessibility and its complexity. We will present the ongoing development of an in silico model of the ecosystem, in interaction with its environment and its host. Our aim is to provide a virtual platform for knowledge and data integration, and simulation. A focus will be made on the structuration of the ecosystem into functional populations. We show how Whole Genome Sequencing (WGS) data from metagenomic analyses can be used to analyse the structure of carbohydrates degradation-related functions. These data give an insight of the gene content of an entire microbial community, even if the organisms that compose it cannot be cultivated. In addition to the potential of conventional molecular inventory techniques (such as targeting ADNr16s), which allows an analysis of diversity, WGS approaches provide an access to the functions. We show how the information obtained can be integrated in the model and discuss the underlying modelling hypotheses.

15:25 to 15:55 Afternoon Tea INI 1
15:55 to 16:30 Plenary Lecture 12: Determining the microbial population dynamics of anaerobic digestion using metagenomics
Co-authors: Henry Nicholls (University of York), Kelly Redeker (University of York), Peter Ashton (University of York)

Anaerobic digestion (AD) is a process that uses microbial consortia to convert organic waste to methane and carbon dioxide (“biogas”) that can be burned to generate heat and electricity. This technology can be applied to both liquid and solid wastes and is in common use. While there is a broad understanding of the principles of AD, the dynamics of the microbial populations involved in AD are still poorly characterised. Recent advances in next generation DNA sequencing technologies (NGS) have made shotgun sequencing of samples a cost-effective means for determining the composition of microbial populations. We are using NGS to build a detailed catalogue of the microbes present in a bench-scale AD system and to track the dynamics of this microbial community with the goals of identifying those species that are essential for the degradation of specific molecules and how the conflicting requirements of different members of the population are met.
16:30 to 17:05 Plenary Lecture 13 (teleconference): tba INI 1
17:05 to 17:20 Contributed Talk 4: Metabolic Modelling in an Evolutionary Framework Predicts Phenotypic Diversification of E.coli growing on Glucose as the Single Carbon Source
Co-author: Orkun S. Soyer (University of Warwick)

Understanding microbial communities is of great importance to monitor and manipulate complex ecosystems like anaerobic digesters, wastewater removal systems or the human gut. A variety of modelling approaches have been presented to simulate microbial communities, however many imply an optimization acting at the community level, an assumption which is not well grounded in evolutionary theory. We here present an evolutionary algorithm that uses multiple instances of flux balance analysis (FBA) models and density dependant selection as the fitness function, leading to the coexistence of different phenotypes of an Escherichia coli core FBA model after 500 rounds of simulated batch-transfers in a minimal medium with Glucose as the only carbon source. The solutions are “selfish” in the way that the only optimization is to maximize individual growth rate, yet they are affected by the metabolic layout of all other members in the community through a shared culture medium. We suggest that such self-optimizing models could be used to study complex microbial communities, where competition, cross-feeding, syntrophy, symbiosis and all forms of microbial interaction arise as emergent properties of the individual optimization of the member organisms.

17:20 to 17:35 Contributed Talk 6: Metaproteomics of algal blooms INI 1
19:30 to 22:00 Conference Dinner at Gonville and Caius College
Friday 12th September 2014
09:30 to 10:05 K Drescher ([Max-Planck Institute for Terrestrial Microbiology])
Plenary Lecture 14: Development and Evolution in Environmental Biofilms
Co-authors: Carey Nadell (Princeton University), Howard Stone (Princeton University), Ned Wingreen (Princeton University), Bonnie Bassler (Princeton University)

Biofilms are antibiotic-resistant, sessile bacterial communities that occupy most moist surfaces on Earth and cause chronic and medical device-associated infections. Despite their importance, it is largely unknown how bacteria organize their behavior inside biofilms, and how biofilms behave in natural environments. In this talk I will focus on how environmental aspects of natural habitats lead to the evolution of simple cooperative behaviors in biofilms. I will also demonstrate how biofilm development and the complex geometries of natural habitats interact to cause the sudden and rapid clogging of porous materials like soil, water filtration devices, and medical stents.
10:05 to 10:40 Plenary Lecture 15: Geomicrobial kinetics: bridging the gap between laboratory and nature
Rates of natural microbes are a key parameter of theoretical and practical problems in environmental chemistry, microbiology, and biotechnology. Empirical models, such as the Monod equation, are standard tools for predicting microbial rates in laboratory and industrial reactors. But direct application of these models to natural environments often overestimates the significance and extent of microbial processes by orders of magnitude relative to field observations. Hence new theories and modeling approaches are required for quantifying microbial metabolism in natural environments and for simulating population dynamics of natural communities. The new theory of geomicrobial kinetics must account for dramatic differences in growth conditions between laboratory reactors and natural environments. For example, the energy available in the environment limits the metabolism of natural microbes, which can be described using the thermodynamic potential factor. According to this factor, the thermodynamic control becomes negligible where the available energy is much larger than the energy saved by microbes. But for common anaerobic respiration of natural environments, the thermodynamic control is significant because the available energy is of the same order of magnitude as the saved energy. The new theory also needs to address (1) how microbial diversity controls the rates of microbial metabolism; (2) what metabolic strategies microbes have to employ in natural environments and how these strategies impact microbial rates; and (3) how to integrate mechanisms and kinetics at different scales, from subcellular scale of enzyme kinetics and cellular scale of microbial kinetics to the field scale of watersheds and aquifers and global scale of element cycling. These questions represent current challenges of geomicrobial kinetics, and can be addressed by integrating the exciting advances in genome-scale modeling, microbial ecology, and environmental chemistry.
10:40 to 10:55 Contributed Talk 5: Uptake levelling in chemotactic bacteria measured by the Gini index
Co-author: Raymond E. Goldstein (University of Cambridge)

Classic experiments on the accumulation of ducks around distinct food sources found consistency with the `ideal free' distribution in which the local population is proportional to the local supply rate: the animal behaviour smoothes the individual uptake over the population. Motivated by this, we examine the analogous problem in the microbial world: the distribution of chemotactic bacteria around multiple nearby food sources and their associated uptake. Through a series of simple models we illustrate how chemotaxis, nutrient consumption, and diffusion of both bacteria and nutrients conspire to produce spatial distributions with unequal resource uptake. It is suggested that the Gini index, well known in theoretical economics, provides a useful quantification of these effects.
10:55 to 11:25 Morning Coffee
11:25 to 11:55 Plenary Lecture 16: Collective Functionality Through Microbial Individuality
According to the conventional view, the properties of an organism are a product of nature and nurture - of its genes and the environment it lives in. Recent experiments with unicellular organisms have challenged this view: genetically individuals living in homogeneous laboratory environments can have markedly different properties, and express different sets of genes. We are interested in the functional consequences of this variation in bacteria: is phenotypic heterogeneity sometimes beneficial, and does it provide microbes with new functionality in their natural environment? I will first present results that suggest that, for the majority of the genes in a bacterial genome, natural selection acts to reduce phenotypic variation. Then, I will present a few exception to this rule, and discuss how phenotypic variation in clonal populations of bacteria can promote interactions between individuals, lead to the division of labor, and allow clonal groups of bacteria to cope with envi ronmental uncertainty. Finally, I will present recent results that indicate that phenotypic heterogeneity in bacterial populations does not only arise through individual molecular decisions in single cells, but is also shaped by interactions between cells that impact the expression of their phenotype. The main conclusion from this work is that microbial individuality can provide groups of organisms with collective functionality.
11:55 to 12:30 Plenary Lecture 17: Micro-scale biological interactions shape microbial community dynamics on marine particles
Particulate organic matter in aquatic environments represents a major source of nutrients for heterotrophic bacteria. To access these nutrients microbial communities need to assemble on particles and, once the ecological opportunity expires, disassemble to start migration and colonization of new nutrient sources. Because of the enormous diversity of microbes in the environment, this process is likely to involve a large number of species interacting at different points during assembly and disassembly. Using a model system based on chitin-associated communities from the coastal ocean, I will discuss ongoing work aimed at studying community assembly on particles as the behavior of a multi-species system, which we attempt to reconstruct with a combination of computational and experimental tools. Our results show that community assembly on chitin involves the fast succession of a large number of species. These complex dynamics are not driven by changes in substrates, but by local biological interactions and ecological trade-offs which structure communities at micro-meter scales. Overall, this study shows that ecological interactions impose strong selective pressures on particle-attached communities and in that micro-scale ecological processes can have a large impact on global ecosystem processes.
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