This page is archived

Links to external sources may no longer work as intended. The content may not represent the latest thinking in this area or the Society’s current position on the topic.

Microbial ecology for engineering biology

28 - 29 March 2022 08:00 - 16:00

Theo Murphy scientific meeting organised by Professor Thomas Curtis and Dr Jane Fowler.

Open engineered microbial systems have a crucial role to play in the development of sustainable technologies for the 21st century. The solution, ecology-based design of engineered biological systems, is urgently needed. This meeting united disciplines by integrating ecological theory with microbial ecology and engineering aims. The meeting spanned the scales from genome to the systems. The organisers of this meeting believe that engineering across these scales will accelerate progress in the many systems where researchers’ engineering aspirations can be met by exploiting the power of microbial communities. 

Attending this event

This event has taken place. 

Enquiries: contact the Scientific Programmes team.

Organisers

  • Professor Thomas Curtis, Newcastle University, UK

    Tom Curtis journey in engineering biology began at school reading 'Invisible Allies' by Bernard Dixon, a book showing microbes as a force for good in the world. After a BSc in microbiology at Leeds he joined the Public Health Engineering research team lead by Duncan Mara. There he learnt that Engineers knew how to put Dixon’s words into action. Working in Northeast Brazil on wastewater treatment systems he gained an MEng and PhD in Public Health Engineering (starting up and managing Aqaba’s wastewater treatment plant in-between). After two years working on public health policy for the UK government he became a Lecturer in (now Professor) of Environmental Engineering in Newcastle University. His core interest is now the engineering of real open microbial systems. His abiding belief is that these systems obey a suite of fundamental and universal rules that can be used in design and management to unlock the power of engineered biological systems.

  • Dr Jane Fowler, Simon Fraser University, Canada

    Dr Jane Fowler is an Assistant Professor of Environmental Microbiology at Simon Fraser University. Her research focuses on water quality and microbial biotechnology in biological drinking water treatment, wastewater treatment and pollutant biodegradation. A major goal of her work is to develop a mechanistic understanding of microbial community structure and function that is guided by ecological theory, microbial physiology and modelling and to apply this to engineered biological systems. This will ultimately improve sustainable biotechnologies for drinking water, wastewater and contaminant treatment using open microbial communities, improving both ecosystem and public health while making strides towards achieving sustainable development goals. Dr Fowler was awarded a PhD in Environmental Microbiology from the University of Calgary. She completed postdoctoral training as a Marie Curie fellow at the Technical University of Denmark, Department of Environmental Engineering.

Schedule

Chair

Dr Jane Fowler, Simon Fraser University, Canada

Professor Thomas Curtis, Newcastle University, UK

Dr Joe Weaver, Newcastle University, UK

08:00 - 08:10 Opening remarks & scene setting

Dr Jane Fowler, Simon Fraser University, Canada

08:10 - 08:30 Global Challenges and Opportunities for Engineering Biology

Dr Andy Lawrence, UKRI-EPSRC, UK

08:30 - 09:00 Engineering biology is a broad church that is united by the need for predictive population biology models

Engineering biology has become synonymous with synthetic biology where genes are snapped together, with Lego-like ease, to go beyond the natural metabolic diversity of microorganisms and deliver novel biotechnologies. The molecular microbiology toolkits of synthetic biology are awe-inspiring. However, for the biotechnologies to be effective and financially viable then the artificial organisms or consortia must persist and continue to function as intended. Any modification of the genetic code will affect an organism's fitness. Thus, it is desirable to know the fate of organisms a priori when exposed to the vagaries of real-world engineered or natural environments. In most engineering disciplines, ease of construction is a secondary facet of a design. First and foremost, the engineer must anticipate failure and use mathematical models to build a product that is robust and resilient. This principal needs to be adopted for all engineered biological systems, synthetic or otherwise, if engineering biology is to realise its full potential and to sit alongside more established engineering disciplines in delivering solutions in a timely and cost-effective manner. This paper demonstrates the vulnerability of synthetic organisms and the potential for even the most parsimonious of population biology models to yield insights on designing resilient systems. 

Professor Bill Sloan, University of Glasgow, UK

09:10 - 09:40 Icebreaker activity
09:40 - 10:00 Coffee break
10:00 - 10:15 Ecological structural instability as a perversive mechanism controlling ecosystem structure and dynamics

A natural question to ask in applied microbial ecology is to what extent our understanding of the ecology of large, multicellular organisms can be transferred to microorganisms. To answer it, it might help to lean on the emerging consensus that there is an explanatory separation between ecological processes involving just two or a few species on one hand, and processes involving large numbers of species and large spatial and temporal scales on the other. The latter, it appears, can be understood without a detailed understanding of the former. The underlying great unifier is a phenomenon called ecological structural instability. It denotes a high sensitivity of local ecological communities to press perturbations or species invasions that arises as species richness reaches a certain critical value from below. This high sensitivity easily leads to species extinctions, which is why in nature species richness tends to saturate shortly below the critical value. This value and other macrocological phenomena, which Dr Rossberg will discuss, are controlled essentially only by the mean, variance, and correlation of the distribution of interaction strengths between species. Details don’t matter. In what forms this leads to parallelism between microbial and traditional macroecology is an exciting question we should address. 

Dr Axel Rossberg, Queen Mary University of London, UK

10:15 - 10:30 Engineering light-driven microbial syntrophies for the generation of value-added products from waste

In environmental biotechnology, microbial transformations of organic molecules are often carried out by a microbial community as opposed to one single type of microbe. Within these communities, microorganisms are forced to interact with each other. In the most general case, microbes compete for space, a resource needed by all community members. More specific interactions may involve competition for shared substrates or a mutual requirement for each other's metabolic products. Understanding the network of interactions between the members of an existing community may enable us to introduce and maintain in an augmented community a thermodynamically possible but currently unrealised ecosystem function. This reasoning was successfully used to engineer a granular, phototrophic and methane-consuming community, able to convert dissolved methane into biomass without externally supplied oxygen. Despite competition for oxygen with traditional heterotrophic respiration, the initially introduced methanotrophic activity was maintained over prolonged times in a continuously operated reactor system. Microbial community analysis revealed that a more complex foodweb established than anticipated. Methane oxidation likely involved subsequent steps of partial oxidations by different bacteria, and possibly even intergranule dependencies. Theoretical considerations are a necessary starting point but need to be sufficiently backed up by experiments to account for unexpected behaviour.

Dr Kim Milferstedt, INRAE-LBE, France

10:30 - 10:45 Unravelling the ecological processes shaping bacterial communities

Professor Joana Falcão Salles,University of Groningen, The Netherlands

10:45 - 11:15 Discussion

Chair

Mr Ramis Rafay, Simon Fraser University, Canada

Professor Thomas Curtis, Newcastle University, UK

12:15 - 12:30 The influence of dispersal in biological treatment

Microbial communities in open microbial systems such as activated sludge are subject to a continual influx of microbes in the influent stream. The microbes entering the system have a range of fates – they may die within the system, leaving behind organic matter, they may pass through the system with little impact, or they may exhibit a positive growth rate and become a permanent member of the community. At a high enough rate, this continual immigration of organisms can have a disproportionate impact on the structure of a local community, which, in ecological terms, is referred to as the mass effects archetype of community assembly. In this talk, Dr Fowler will discuss the prevalence of mass effects within biological treatment systems and present estimates for migration rates within different systems. Dr Fowler will then consider the potential consequences of this archetype on the structure, function and stability of microbial communities.

Dr Jane Fowler, Simon Fraser University, Canada

12:30 - 12:45 Unraveling and rewiring anaerobic microbiome metabolism with microbial systems ecology

Microbial communities (‘microbiomes') have been employed to benefit society for thousands of years. However, the vast majority of the microbial world’s transformative capabilities have yet to be unlocked and harnessed for engineering applications. A key reason for this is the lack of tools available to quantitatively probe and experimentally discover the structure and in situ activity (ie fluxes) of biochemical networks operating in poorly characterised and uncultivated microorganisms. While understanding and control of microbiome metabolic flux is the ultimate goal, Dr Lawson and his team have started with unraveling metabolism and fluxes in anaerobic microbes and microbial communities driving anaerobic ammonium oxidisation (anammox) and anaerobic fermentation. Together, these microbiomes are responsible for controlling nitrogen and carbon cycling on a global-scale and for performing sustainable wastewater treatment and resource recovery through complex metabolic interactions. Dr Lawson will show how isotopic tracers combined with quantitative metabolomic analysis were used to probe and illuminate the biochemical pathways operating in anammox bacteria. He will also discuss how the integration of metagenomics, 13C-metaproteomics, and metabolic modeling were used to determine metabolic interactions between anammox, nitrifying, and denitrifying bacteria in complex microbiomes. These analyses have resulted in several key discoveries on the enigmatic metabolism of anammox bacteria and their metabolic interactions with other poorly characterised nitrogen cycle bacteria. He will conclude with discussion on preliminary efforts to assemble and engineer synthetic consortia of anaerobic fungi and bacteria to recover valuable products from renewable biomass, while unmasking basic principles for microbiome engineering.

Professor Christopher Lawson, University of Toronto, Canada

12:45 - 13:00 Linking microbial community types, their community structure and functional processes to lung disease in cystic fibrosis airways

People with cystic fibrosis (CF) suffer from persistent, poly-microbial infections in the lung. This CF lung microbiome is a dynamical, evolving ecosystem that displays classic features of a complex system. It shows temporal changes in composition, is spatially stratified in the alveolar microenvironment and microbial interactions generate an ecological dependency structure in the community. The emergent disease dynamics are characterised by abrupt inflammatory aggravation (pulmonary exacerbations) that cause irreversible lung damage and drive patient mortality. The working hypothesis is that dysbiosis and metabolic niche reconstruction are relevant drivers of lung exacerbation. However, a strong patient-specificity of the microbiome composition as well as hyper-stable community dynamics currently limit advances in the field. Dr Widder works at the interface of complex systems, data science and microbial ecology. She will present an overview on her work about the CF lung microbiome and will discuss different theoretical angles employed for overcoming system-specific challenges. Her future vision is a rational, model-based design of interference strategies that exploit underlying ecological dependencies of the microbial community and enable controlled microbiome management. The treatment would aim to avoid microbial dysbiosis, reduce lung exacerbation and thereby prolong patient’s lives.

Dr Stefanie Widder, Medical University of Vienna, Austria

13:00 - 13:30 Discussion
13:30 - 14:00 Small group discussions on applying whole systems approaches
14:00 - 14:30 Tea
14:30 - 15:00 Feedback on small group discussions in plenary

Chair

Mr Ramis Rafay, Simon Fraser University, Canada

15:00 - 15:15 Targeted DNA editing within microbial communities

Functional understanding of microbial DNA is largely based on isolate genetics, where the effects of genetic manipulations on cultivable organisms are observed in isolation. Unfortunately, this provides limited insight into the workings of genes in the complex and societally relevant microbial communities that exist in nature. In order to move beyond the paradigm of manipulating microbes in confinement, Dr Rubin and collaborators have created a generalisable toolset for targeted genome editing of individual organisms within complex microbial communities. First, they have developed environmental transformation sequencing (ET-Seq) to determine in situ which microbes within a community can be edited by untargeted transposases, and with what efficiency. Second, they have repurposed RNA-guided CRISPR-Cas transposases to paste customised DNA into unique target sites within the genomes of specific microbes in a community. Third, they have applied these technologies to enrich, isolate, and track fitness of genetic mutants in soil and infant gut microbiota. The ability to make organism- and locus-specific changes within microbiomes will lead to improved understanding of microbial communities and enable meaningful modification of them.  

Dr Benjamin Rubin, University of California, Berkeley, USA

15:15 - 15:30 Microbial community assembly processes

Process control of complex microbial communities grown in bioreactors should aim to create a niche defined by boundaries to strengthen and maintain an initially formed microbial community. Steady-state operated bioreactors are designed to reduce the effects of environmental factors on cultivated organisms, but have been shown to greatly increase the variability of community structures over long periods of time. Therefore, new ideas for reactor configurations that could lead to stabilization of community structures are needed.  Flow Cytometry as a rapid detection and assessment method was used to monitor assembly processes of microbial communities within bacterial generation times. Bioinformatics tools were used to interpret these data. Selected taxonomic sequencing of whole communities and sorted subcommunities supported the findings. The results suggest that synchronizing complex microbial communities in insular steady-state environments or keeping them in their original or desired structure can be difficult. In addition, the stability paradigm was studied in such insular environments and a fast workflow for monitoring and calculating the stability properties resistance, resilience, displacement speed, and elasticity was developed.

Professor Susann Müller, Helmholtz Centre for Environmental Research - UFZ, Germany

15:30 - 15:45 Viruses' potential roles in carbon and nitrogen cycling during benzene degradation under nitrate-reducing conditions

In this study, the researchers monitored the succession of viruses and prokaryotes in a microcosm experiment during different phases of benzene mineralisation under nitrate-reducing conditions in coarse sand. Nitrate-dependent benzene mineralisation was monitored by the addition of 13C-labelled benzene and subsequent analysis of generated 13CO2. They collected solid (sand) and liquid samples at five-time points (three biological replicates per time point) for DNA extraction and shot-gun whole-genome sequencing. A total of 24 metagenomes (Illumina, 2x125 bp, 25 Mio reads) were analysed. Functional annotation of the 222 vOTUs identified 91 genes encoding 13 proteins relevant to benzene mineralisation coupled to nitrate reduction. Regarding carbon cycling, genes related to anaerobic degradation of benzoyl-CoA, and CO2 fixation using the Wood-Ljungdahl pathway were found in our vOTUs. Similarly, genes related to nitrate reduction to nitrite, nitrite reduction to N2, and nitrite reduction to ammonium indicate the viruses' potential contribution to the nitrogen cycle. Preliminary analysis using PHACTS suggested that 160 vOTUs (72.1%) have a lytic life cycle, indicating a potential role of viruses in carbon and nitrogen cycling. The researchers' data demonstrate the potential relevance of viruses in anaerobic benzene degradation and open new doors for the study of viruses in anaerobic ecosystems.

Dr Ulisses Nunes da Rocha, Helmholtz Centre for Environmental Research, Germany

15:45 - 16:15 Discussion
16:30 - 17:30 Poster session

Chair

Dr Joe Weaver, Newcastle University, UK

Professor Thomas Curtis, Newcastle University, UK

Dr Jane Fowler, Simon Fraser University, Canada

08:00 - 08:05 Welcome and review of yesterday

Professor Thomas Curtis, Newcastle University, UK

08:05 - 08:35 Engineering Open Biological Systems

The Engineering of Open Biological Systems requires a distinct philosophy, and an approach, that can cope with the unknown. For all open systems are, at best, only partially characterised or indeed characterisable. Fortunately, this is in the best traditions of modern engineering.  When one is in complete ignorance the simplest thing to do is to experiment and gain a ‘black box” understanding.  This is arguably the 'state of the art' and has been since about 1914 because it works, but it is slow. Experiments take months or years and only a small range of solutions can be considered.  There are two alternatives: both valid and both grounded in theory.  The first is to use 'broad-brush' descriptions of the system. Such approaches can be very powerful in telling you what will happen in very abstract terms to systems that are already established.  But what they cannot do, is tell you how a whole new system will perform.  This is because the properties of engineered open systems are emergent, not a function of any single taxon, but of interacting taxa. This is why naïve experimentation works: they produce the results, the emergent properties, of complex systems. It is also the reason that more sequencing and more science does always not work. The properties of the system cannot be understood by one individual in isolation, their interactions are vital. Emergent properties can be characterised by individual based models that capture those interactions. The benefits of so doing are manifold.  We can shorten experimental times, and so accelerate the development of new technologies. We can also incorporate science into decision making.  It is faster and cheaper to incorporate a new genome into a modelling scheme than to run a real-life experiment to test a particular prediction about that genome.  There are, of course, computational limits to such an approach.  These limits can be transcended with machine learning and AI.  There is scope for many new technologies in open biological systems. Their implementation will be vastly accelerated by the introduction of the new simulation methods we propose.

Professor Thomas Curtis, Newcastle University, UK

08:35 - 08:50 Discussion
08:50 - 09:05 Complete ammonia oxidation: predictions versus observations

Nitrification, the oxidation of ammonia to nitrate, is an important part of the Nitrogen cycle. It was always believed to be carried out in two steps, (incomplete) oxidation of ammonia to nitrite followed by further oxidation of nitrite to nitrate. In 2006, complete ammonia oxidisers or comammox, oxidising ammonia directly to nitrate, were predicted to have a higher growth yield but a lower specific growth rate based on kinetic theory. Comammox were thought to be more competitive than incomplete ammonia oxidisers in environments such as biofilms, which were predicted to select for higher growth yield rather than faster specific growth rate. The independent discovery of comammox in biofilms by two groups in 2015 was consistent with the predicted fitness advantages of comammox, but how well have predictions stood the test of time so far? Dr Kreft will compare the evidence to date with his team’s predictions of comammox growth characteristics and the environmental conditions where it was expected to be abundant or dominant.

Dr Jan-Ulrich Kreft, University of Birmingham, UK

09:05 - 09:20 Modelling of engineered biological systems

Mixed bacterial cultures are fundamental for engineered biological systems, in particular wastewater treatment. Microbes do not function in isolation but are members of communities that are complex adaptive systems. The coherent behaviour of the community arises from a variety of interactions between microbes as well as with their local environment, and some properties of the communities are not present in individual microbes. The activity at micro-scale determines the properties we measure at the macro-scale. As such, there is a wide variety of mathematical models that can be developed in order to describe and predict the microbial community behaviour. They vary from models of the mechanisms determining community assembly to the ASM/AD models used currently in plant design. Ideally, one would want to predict and understand the emergent properties using multi-scale models but it is a big challenge to model processes across different time and spatial scales. Nevertheless, bridging the gap between the macro and micro-scales would give engineers new tools that would enable them to better understand, design and optimise the novel technologies.

Dr Dana Ofiteru, Newcastle University, UK

09:20 - 09:40 Discussion
09:40 - 10:10 Coffee
10:10 - 10:25 Genome-scale metabolic modeling of microbes and microbial communities

Genome-scale metabolic reconstructions of bacteria can be used to study how microbes and microbial communities interact with each other, their environment, or their hosts. Several platforms exist to automatically create metabolic reconstructions directly from genomes, but the resulting reconstructions often need refinements in order to accurately model the organism’s known metabolic functions, which is necessary when the goal is to use metabolic reconstructions to engineer a microbe or community. The DEMETER pipeline was developed to simultaneously reconstruct and refine a myriad of microbes at the same time. It was used to create the Assembly of Gut Organisms through Reconstruction and Analysis (AGORA), and its successor, AGORA2, which is comprised of 7,206 human gut microbial strains, while ensuring that the resulting metabolic reconstructions agreed with available experimental data and adhered to the quality standards accepted by the metabolic modeling community. The resulting metabolic reconstructions can for example be used to model microbial metabolism, metabolic exchanges within microbial communities, or microbial interactions with their host. Additionally, these metabolic reconstructions can be combined with ‘omics’ data sets for context-specific modeling of microbial metabolism.

Dr Stefanía Magnúsdóttir, Helmholtz Centre for Environmental Research, Germany

10:25 - 10:40 Towards predicting bacterial community dynamics using spatiotemporal metabolic models

Similar to the uneven distribution of human communities on Earth, bacterial life in natural environments is highly localised. Regions of elevated bacterial activity (such as the rhizosphere or marine particles) are subject to steep oxygen and resource gradients spanning a range of metabolic strategies - and interrogating the spatial organisation and nutrient dynamics in situ remains challenging. Linking genome-scale metabolic network models with realistic representations of the physical environment offer a means for bridging the observational gap by reproducing the metabolic versatility and emerging nutrient landscapes of microbial hotspots in silico. Here dynamic flux balance analysis is used to predict the emergent bacterial community composition grown on various primary carbon sources in well-mixed conditions and in complex porous environments. Model predictions were evaluated experimentally by quantifying the abundances of the four community members grown on the same carbon source using qPCR for the well-mixed scenario. The model reliably predicts the emergent community structure governed by myriad trophic interactions without making a priori ecological assumptions. The researchers conclude that spatiotemporal metabolic models that consider realistic representation of microbial habitats at the cellular scale offer unprecedented opportunities for deciphering bacterial interactions in complex habitats not yet observable with existing experimental approaches. 

Dr Benedict Borer, MIT, USA

10:40 - 11:00 Discussion
11:00 - 12:00 Lunch
12:00 - 12:15 How encounters at the microscale prime microbial ecosystems

Encounters between cells are central to the role of microorganisms in global biogeochemical cycles, plant growth and human health. In the ocean, prominent examples include marine snow formation by elongated phytoplankton following a phytoplankton bloom or bacterial encounter with and subsequent degradation of marine snow responsible for carbon export from the upper ocean in the biological pump. Such encounters are typically modeled as encounters between spheres, building on the models of gasses, coagulating colloids and rain formation. However, these physics-based approaches only effectively account for microorganisms' traits. Yet, microorganisms' traits combined with environmental conditions have a large impact on key encounters at the ocean microscale with implications for many ecological processes. For example, cell shape, in conjunction with buoyancy and turbulence, can speed up the formation of marine snow by elongated phytoplankton nearly ten-fold, providing a mechanistic explanation for the rapid clearance of many phytoplankton blooms. Finally, random encounters can be harnessed - Trichodesmium, a key marine nitrogen fixer, uses smart reversals to convert random encounters between cells into organised aggregates.

Dr Jonasz Slomka, ETH Zürich, Switzerland

12:15 - 12:30 Individual-based modelling and simulations of microbial systems using NUFEB

Individual-based microbial modelling (IbM) is a bottom-up approach to study how the heterogeneity of individual microorganisms and their local interactions influence the behaviour of microbial communities. In IbM, microbes are represented as particles endowed with a set of biological and physical attributes. These attributes are affected by both intra- and extra-cellular processes resulting in the emergence of complex spatial and temporal behaviours, such as the morphology of microbial colonies. In this work, an Ib simulator NUFEB is developed for modelling 3D dynamics of microbial communities at microscale. The novelty of NUFEB lies in its parallelisation and generic model specification, enabling realistic modelling and simulation of systems with over 10^7 microbes and a wide range of biological, physical, and chemical processes at millimetre scale. NUFEB also allows incorporating a machine learning-based approach for community-system upscaling. This is achieved by training a dynamic emulator to predict macroscale behaviour using a large number of IbM simulation outputs. In this talk, Dr Li will give an overview of the NUFEB functionalities, showcase the type of microbial systems NUFEB can be used to model and simulate, and demonstrate the upscaling strategy. Simulation examples include Anammox biofilm formation, biofilm detachment under fluid flow, and minicell (synthetic chassis) formation. 

Dr Bowen Li, Newcastle University, UK

12:30 - 12:50 Discussion
12:50 - 13:10 Small group discussions on approaches at various scales
13:10 - 13:30 Discussion on multiscale in plenary
13:30 - 14:00 Tea
14:00 - 14:30 Merging theory and practice: a discussion on feasibility of and challenges to microbiome engineering

Dr Michaeline Albright, Allonnia, USA

14:30 - 15:00 Small group discussions on feasibility, obstacles
15:00 - 15:40 Discussion on feasibility and obstacles in plenary
15:40 - 16:00 Wrap up, next steps, farewell

Professor Thomas Curtis, Newcastle University, UK

Dr Jane Fowler, Simon Fraser University, Canada