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The microbiome: human medicine and agriculture in a microbial world

05 October 2018 08:00 - 18:00

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This one-day conference held by the Royal Society will bring together experts from both agricultural and human microbiome sectors to discuss the barriers to technology translation and common principles across both sectors. Speakers will discuss the challenges in determining microbiota through to the dynamic forces determining colony structures. The meeting will also explore intentional modulation of microbial populations to develop medical therapeutics and improvements in agricultural productivity, covering technical challenges in determining causation and methods to drive the technology forward.

Attending this event

This open event is free to attend and is intended for those with an interest in the life sciences sector, from a variety of backgrounds including academia, industry, government, as well as regulatory, charitable and other scientific bodies.

Contact the Industry team for more information.

About the conference series

This meeting forms part of the Royal Society’s Transforming our Future series. The meetings are unique, high-level events that address scientific and technical challenges of the next decade and bring together leading experts from wider scientific community, industry, government and charities.

Organisers

  • Dr Mike Romanos, CEO Microbiotica

    Mike is co-founder and CEO of Microbiotica, which is commercialising leading microbiome science from the Wellcome Sanger Institute. He has 30 years’ experience in the biotech and pharma, previously co-founding Crescendo Biologics which he led as CEO and CSO for six years, building a leading discovery platform and pipeline in antibody fragment-based therapeutics. Prior to that he held senior global roles in GlaxoSmithKline over 10 years, during which time he built trans-national innovative R&D organisations which contributed to the company’s platforms and pipeline across therapeutic areas and across multiple product types, latterly as VP for Genomics/Target Discovery.

    Mike is highly experienced in biotech translation and commercialisation, serving as a Trustee on the LifeArc Board, and previously Translator in Residence at Imperial College, Venture Partner for UK Innovation and Science Seed Fund, and member for MRC’s Developmental Pathway Funding Scheme panel.

    Mike’s academic work included research in influenza virology (MRC, National Institute for Medical Research) and in yeast genetics and biotechnology (University of Leicester). He holds a degree in Natural Sciences from Cambridge University, a PhD in Molecular Virology from Imperial College, and is a Fellow of the Royal Society of Biology. 

  • Professor Richard Flavell CBE FRS

    Richard Flavell is a plant geneticist who has focused much attention on traits important in crop plants. In the last five years he has served as Chief Scientist in two companies in the USA. The first, Indigo, Cambridge, Massachusetts is an agricultural microbiome company. The second, Inari, is an agricultural plant genetics company.

    He is currently a consultant for companies and public sector organizations committed to plant improvement, including the International Wheat Yield Partnership.

    After his undergraduate degree in microbiology and his PhD in the John Innes Institute and the University of East Anglia, he spent two years of postdoctoral research in Stanford University, California. He then joined the Plant Breeding Institute in Cambridge (UK) where he built up a large Department of Plant Molecular Genetics between 1969 and 1987. He was then appointed as Director of the John Innes Centre (JIC), Norwich and to a chair at the University of East Anglia and oversaw a large expansion of JIC’s activities and impact.

    In 1998 he became the Chief Scientific Officer of Ceres, a young plant genomics company in California. This became a public company and was recently bought by a multinational agricultural company.

    He is a Fellow of the Royal Society and a Commander of the British Empire for services to science.

Schedule

09:15 - 09:20 Welcome to the Royal Society

Sir John Skehel FMedSci FRS, Vice-President and Biological Secretary, The Royal Society

09:20 - 09:30 Chair Remarks

Professor Richard Flavell CBE FRS

Chair

Professor Richard Flavell CBE FRS

09:30 - 10:00 Microbiome Progress and Opportunities - Past, Present and Future

Over the last decade, there has been considerable progress in our understanding of microbiomes and their relationship to human health and disease. In addition, there has been a re-invigorated interest in the importance of microbiomes in animal production and environmental sustainability.

Microbiome parameters such as diversity, ecology and functionality are important determinants of health-/disease-risk. To understand this complexity, high-throughput sequencing and bioinformatic approaches have been adopted to accurately evaluate perturbations in microbiome communities and to provide high quality, high resolution (strain level) analyses of both healthy and dysbiotic ecosystems. The importance of aligning microbiome composition to community function, has also driven a greater integration of multi-omics technologies. A combination of human intervention and mechanistic animal studies has underpinned our current understanding of how microbiomes impact diverse aspects of human biology.

The functional microbiome has driven the rapid growth of the translational microbiome. This industry is supported by significant public and private funding/investment and is focused on discovery and delivery of disruptive microbiome-based interventions, to prevent and treat human diseases.

Professor Denise Kelly, Seventure Partners

10:00 - 10:30 Increasing Agricultural Productivity: The Continuum of Breeding, Biotech and Microbial Products

Over the past century, application of science to agriculture has enabled dramatic increases in productivity across the developed and the developing world. Throughout this period, the science and tools leveraged to improve agricultural productivity have continued to evolve, as has underlying knowledge. In parallel, developments in molecular biology over the past 50 years have ushered in GM crops (most of which incorporate genes from microbes into plants) and their widespread use across broad areas of agricultural production.

While several microbial technologies, such as rhizobium, have been important to agriculture for several decades, emerging capabilities are advancing a new wave of microbial inputs into mainstream agricultural production. Today’s microbial products have demonstrated an ability to improve crop performance under a wide range of stresses spanning heat, water, nutrients and pests. Development of these products draws on the solid foundations of agricultural research while increasingly leveraging deep insights spanning microbes, their communities, seed genetics, agronomic practices and growing environments.

Dr Ray Riley, Ret. Senior VP Product Development, Indigo

Chair

Dr Mike Romanos, CEO Microbiotica

11:05 - 11:25 Data driven knowledge discovery applied to the human gut microbiome

Metagenomics, the analysis of the sum of genetic material from an environmental sample, has started to shed light on the huge diversity of micro-organisms that occupy environments such as the human body, soil and the World's oceans. During this talk, I will provide an overview of how metagenomics is being used to identify the different microbes, many of which have not previously been observed before. There are, however, limitations to this approach that differ across biomes. Despite this, metagenomic approaches are beginning to unveil the so call ‘microbial dark matter’ – the previously unknown biological repertoire – which when harnessed will provide many applications to the medical and biotechnology industries.

Dr Rob Finn, European Bioinformatics Institute

11:30 - 11:50 Microbiomes for improving crop production

For decades, the microbial community in soil has been appreciated as very large and diverse, essential for both terrestrial nutrient cycling and plant health, whilst remaining very poorly understood. The recent advances in sequencing technology and bioinformatics have greatly improved our familiarity with soil and plant microbiomes, and the complex relationship between them. Plants encounter bacteria and fungi in soil which, if they are proficient in utilising plant-derived substrates, proliferate in the rhizosphere. They may colonise the rhizoplane and above-ground parts, some becoming endophytes. Not all are beneficial, but the microbiome is reported to inhibit pests and pathogens, modulate plant growth and improve nutrient acquisition. With global pressure to escalate food production whilst minimising fertilizer and agrochemical use, a better understanding of how to maximise the benefits of the plant microbiome becomes increasingly important.

Professor Penny R Hirsch, Rothamsted Research

11:55 - 12:15 Culture-based microbiome analysis in personalised medicine and birth cohort studies

Studies at the Human Microbiota Interactions lab have addressed key bottlenecks in high resolution strain profiling and functional validation of the gut microbiota through the development of reference genome-based analysis approach that vastly increases the precision and efficiency of metagenomic analysis. Our approach is underpinned by mass isolation of bacteria and generation of a large reference genome sequence database. We call this approach “Precision Metagenomics”. Precision metagenomics underpins studies in HMIL and the Wellcome Sanger Institute spinout company Microbiotica, which has industrialised the platform and is using it for biomarker and therapeutic discovery. The platform and its application will be discussed in the context of a major UK Baby Cohort study aiming to find correlates between early life microbiota development and long-term health and disease.

Dr Trevor Lawley, Microbiotica

12:20 - 12:40 Dissecting the role of multi-kingdom microbial consortia on plant health

Roots of healthy plants are inhabited by soil-derived bacteria, fungi, and oomycetes that have evolved independently in distinct kingdoms of life. How these microorganisms interact and to what extent those interactions affect plant health are poorly understood. We examined root-associated microbial communities from three Arabidopsis thaliana populations and detected mostly negative correlations between bacteria and filamentous microbial eukaryotes. We established microbial culture collections for reconstitution experiments using germ-free A. thaliana. In plants inoculated with mono- or multi-kingdom synthetic microbial consortia, we observed a profound impact of the bacterial root microbiota on fungal and oomycetal community structure and diversity. We demonstrate that the bacterial microbiota is essential for plant survival and protection against root-derived filamentous eukaryotes. Deconvolution of 2,862 binary bacterial-fungal interactions ex situ, combined with community perturbation experiments in planta, indicate that biocontrol activity of bacterial root commensals is a redundant trait that maintains microbial inter-kingdom balance for plant health.

Dr Stéphane Hacquard, Max Plank Institute for Plant Breeding Research

12:45 - 13:05 AgBiome: Harvesting the Plant Microbiome

AgBiome is a biotechnology company applying advanced knowledge of the plant-associated microbiome to create innovative products for agriculture. Our research platform allows us to efficiently capture and screen the most diverse and unique microbes for agriculturally relevant applications. To drive our discoveries, we use our in-depth knowledge of the crop microbiome and an extensive network of field-sampling partners to build an ever-expanding proprietary strain collection. This collection sources the discovery of new biologicals and trait genes for use in disease and pest control.

Unlike many programs which only use metagenomic surveys, the AgBiome platform is focused on isolated microbial strains and their fully sequenced genomes, which gives us unparalleled insight into the detailed genomic composition of crop-associated microbes. Isolate sequences are used to de-replicate the collection and uncover true microbial diversity at an even deeper level than 16S rRNA identity alone. Microbes from our collection are screened in innovative high-throughput assays against a broad range of fungal pathogens, insect pests, and plant-parasitic nematodes. Successful candidates are tested in field trials and confirmed active biologicals proceed through our fermentation and formulation pipeline. As we continue to integrate sequence data with performance data across multiple assays and field trials, the AgBiome team will improve our ability to quickly identify active leads that are attractive product candidates and will begin to correlate the effect of microbe communities on plant health.

Dr Tracy Raines, AgBiome

Chair

Professor Denise Kelly, Seventure Partners

14:05 - 14:25 Host microbiome interactions in health and disease

The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system co-evolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche and multiple environmental factors including our nutritional repertoire and bio-geographical location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant host-microbiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome and even cancer. We have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem, and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multi-factorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments.

Professor Eran Elinav, The Weizmann Institute of Science

14:30 - 14:50 Gut reactions: Immune pathways in the intestine in health and disease

The gastrointestinal (GI) tract is home to a large number and vast array of bacteria that play an important role in nutrition, immune system development and host defense. In inflammatory bowel disease (IBD) there is a breakdown in this mutualistic relationship resulting in aberrant inflammatory responses to intestinal bacteria. In this presentation I will discuss microbial products that promote innate and adaptive immune responses in the intestine and how these may be exploited therapeutically.

Professor Fiona Powrie FRS, Kennedy Institute of Rheumatology, University of Oxford, UK

14:55 - 15:15 A soil-borne legacy: Disease-induced assemblage of a plant-beneficial bacterial consortium

Disease suppressive soils typically develop after a disease outbreak due to the subsequent assembly of protective microbiota in the rhizosphere. The role of the plant immune system in the assemblage of a protective rhizosphere microbiome is largely unknown. We recently demonstrated that Arabidopsis thaliana specifically promotes three bacterial species in the rhizosphere upon foliar defense activation by the downy mildew pathogen Hyaloperonospora arabidopsidis. The promoted bacteria were isolated and found to interact synergistically in biofilm formation in vitro. Although separately these bacteria did not affect the plant significantly, together they induced systemic resistance against downy mildew and promoted growth of the plant. Moreover, we show that the soil-mediated legacy of a primary population of downy mildew infected plants confers enhanced protection against this pathogen in a second population of plants growing in the same soil. Together our results indicate that plants can adjust their root microbiome upon pathogen infection and specifically recruit a group of disease resistance-inducing and growth-promoting beneficial microbes, therewith potentially maximizing the chance of survival of their offspring that will grow in the same soil.

Dr Roeland Berendsen, Utrecht University

15:20 - 15:40 The bovine ruminal microbiome: structure and function

Ruminants provide human society with high quality food from non-human-edible resources, but their emissions negatively impact the environment via greenhouse gas production. The rumen and its resident microorganisms, principally anaerobic bacteria and fungi, protozoa and archaea, dictate both processes. Recently, a 1000 dairy cow study revealed a global core microbiome present in the rumen whose composition and abundance predicted many of the cows’ production phenotypes, including methane emission. Certain members of the core microbiome are heritable and have strong associations to cardinal rumen metabolites and fermentation products that govern the efficiency of milk production. These heritable core microbes therefore present primary targets for rumen manipulation towards sustainable and environmentally friendly agriculture. Furthermore, complementary metagenomics studies in beef cattle have revealed a subset of microbial genes from which methane emissions and feed efficiency (the efficiency of conversion of feed consumed to weight gain) can be predicted. The ruminal microbiome is predominantly determined by the composition of the feed, but the host animal also has a role in determining its composition and function.

Professor John Wallace, University of Aberdeen

15:45 - 16:05 Using the microbiome for immune modulation in inflammatory bowel disease and cancer

This talk will present clinical and preclinical evidence supporting the development of microbiome based drugs consisting of consortia of commensal bacteria. Exploratory clinical studies of fecal transplant have shown a potential therapeutic the role of the microbiome in treating ulcerative colitis. In addition, recent data is now accumulating in solid cancer patients treated with checkpoint inhibitors showing that there is a microbiome correlate of response. This has prompted efforts to evaluate drugs consisting of microbial consortia in these indications. Results of a Phase 1 trial of SER-287 in patients with active mild-to-moderate ulcerative colitis and preclinical results with a SER-401, a candidate for use with checkpoint inhibitor therapy, will be discussed.

Dr David N. Cook, Executive Vice President of R&D and Chief Scientific Officer, Seres Therapeutics

Chair

Dr Mike Romanos, CEO Microbiotica

Panellists (confirmed)

Professor Ian Charles, Director, Quadram Institute

Dr David N. Cook, Executive Vice President of R&D and Chief Scientific Officer, Seres Therapeutics

Dr Ray Riley, Ret. Senior VP Product Development, Indigo

Professor Denise Kelly, Seventure Partners

Professor Penny R Hirsch, Rothamsted Research

Professor Philip Poole, University of Oxford, UK

Professor Richard Flavell CBE FRS