UK Institute of Microbiome Engineering
Lead Research Organisation:
UNIVERSITY COLLEGE LONDON
Department Name: Cell and Developmental Biology
Abstract
he microbes that live within us influence our health and wellbeing. Research has shown changes in the microbiome are linked with inflammatory diseases, diabetes, obesity, cancer and mental health. They can also determine how effective treatments are and how well we recover from surgery. The microbiome has also become a multi-billion-dollar industry, with drug and diagnostic companies racing to capture the market for personalised medicine.
Despite these advances, our understanding of the interactions between the host and the microbiota remain primitive as we do not have the tools to interrogate these systems in a quantitative manner. Here we outline a proposal to build a world- leading multi-disciplinary and multi-centre UK Institute for Microbiome Engineering. This institute will leverage cutting-edge engineering approaches to biology - systems and synthetic biology - to influence and modify the microbiota in well determined ways. This investment will have a huge and significant impact for the NHS over the next 30 years, influencing hospital treatment, home healthcare, disease prevention, mental health and wellbeing.
Despite these advances, our understanding of the interactions between the host and the microbiota remain primitive as we do not have the tools to interrogate these systems in a quantitative manner. Here we outline a proposal to build a world- leading multi-disciplinary and multi-centre UK Institute for Microbiome Engineering. This institute will leverage cutting-edge engineering approaches to biology - systems and synthetic biology - to influence and modify the microbiota in well determined ways. This investment will have a huge and significant impact for the NHS over the next 30 years, influencing hospital treatment, home healthcare, disease prevention, mental health and wellbeing.
Organisations
- UNIVERSITY COLLEGE LONDON (Lead Research Organisation)
- Syngulon (Collaboration, Project Partner)
- CC Biotech Ltd (Project Partner)
- University of Oxford (Project Partner)
- Newcastle University (Project Partner)
- University of Warwick (Project Partner)
- University of Edinburgh (Project Partner)
- University of Manchester (Project Partner)
- Earlham Institute (Project Partner)
Publications
Rutter JW
(2022)
Microbiome engineering: engineered live biotherapeutic products for treating human disease.
in Frontiers in bioengineering and biotechnology
Rutter JW
(2024)
A bacteriocin expression platform for targeting pathogenic bacterial species.
in Nature communications
| Description | We have developed a number of new approaches in the field of microbiome engineering: 1) a new engineering biology platform for the delivery of bacteriocins, bacterial produced antimicrobial peptides. This enables us to design new microbes (engineered live biotherapeutics) that can potentially target specific species of bacteria in the human body. We envisage that this platform can be used in the fight against antimicrobial resistance. It can also be used in combination with existing chemotherapeutic and immunotherapeutic drugs for cancer treatment. 2) new modelling tools to capture the dynamics of microbial communities. This is available in the MIMIC software package 3) a survey of cancer patients and their families on their attiitudes to microbiome engineering |
| Exploitation Route | This delivery platform is general and could be used to express bacteriocins to target any bacteria. This could be used by any academics/clinicians/companies interested in microbiome engineering. The software is freely available for researchers to use. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | As part of the responsible research and innovation (RRI) initiative, we launched a survey to assess current public attitudes towards microbiome engineering with a particular focus on healthcare applications. This work falls under the "Engage" component of the AREA (Anticipate, Reflect, Engage, Act) framework that EPSRC encourages researchers to follow (1). Our work could potentially have a therapeutic purpose for patients with colon cancer in the future, therefore success would be reliant on patients' acceptability towards engineered live bacterial therapeutic product (eLBP). This led us to design a survey to assess the attitudes towards microbiome engineering as a general principle and more specifically engineered live bacteria. |
| First Year Of Impact | 2023 |
| Sector | Healthcare |
| Impact Types | Societal |
| Description | 21EBTA: EB-AI Consortium for Bioengineered Cells & Systems (AI-4-EB) |
| Amount | £1,259,583 (GBP) |
| Funding ID | BB/W013770/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2022 |
| End | 01/2024 |
| Title | Dataset for publication ("An antimicrobial peptide expression platform for targeting pathogenic bacterial species") |
| Description | Experimental dataset used to create Figures 2-4 of manuscript: "An antimicrobial peptide expression platform for targeting pathogenic bacterial species" (preprint doi: https://doi.org/10.1101/2023.10.09.561505). |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | All the data from our publication was made available. |
| URL | https://zenodo.org/record/8427304 |
| Description | Syngulon |
| Organisation | Syngulon |
| Country | Belgium |
| Sector | Private |
| PI Contribution | Working with Syngulon, we have expanded their area of interest from fermentation to helathcare. |
| Collaborator Contribution | Partners brought knowledge on bacteriocins |
| Impact | Development of our bacteriocin expressing platform. New targets in oncology |
| Start Year | 2015 |
| Title | Engineered live biotherapeutic platform for the delivery of antimicrobial peptides |
| Description | We developed a new bacteriocin secretion platform that can be used to target pathogenic species. As a proof of concept we target two Enterococcus species as pathogens of interest, Enterococcus faecalis and Enterococcus faecium. We built on previous works in two main ways. We develop a modular platform based on the CIDAR MoClo assembly standard, which allows for flexibility in part interchange. Additionally we explore four different secretion signal peptides, to add another tunable parameter for eLBP delivery. We then used co-culture assays and Lotka-Volterra modeling to gain insights into the growth dynamics of these strains. Main source of funding was UKRI, EPSRC. |
| Type | Therapeutic Intervention - Cellular and gene therapies |
| Current Stage Of Development | Initial development |
| Year Development Stage Completed | 2023 |
| Development Status | Actively seeking support |
| Impact | It is early stages but has formed the basis of further funding applications. |
| Title | MIMIC |
| Description | MIMIC: A Comprehensive Python Package for Simulating, Inferring, and Predicting Microbial Community Interactions The study of microbial communities is vital for understanding their impact on environmental, health, and technological domains. The Modelling and Inference of MICrobiomes Project (MIMIC) introduces a Python package designed to advance the simulation, inference, and prediction of microbial community interactions and dynamics. Addressing the complex nature of microbial ecosystems, MIMIC integrates a suite of mathematical models, including previously used approaches such as Generalized Lotka- Volterra (gLV), Gaussian Processes (GP), and Vector Autoregression (VAR), plus newly developed models for integrating multiomic data, to offer a comprehensive framework for analysing microbial dynamics. By leveraging Bayesian inference and machine learning techniques, MIMIC accurately infers the dynamics of microbial communities from empirical data, facilitating a deeper understanding of their complex biological processes, unveiling possible unknown ecological interactions, and enabling the design of microbial communities. Such insights could help to advance microbial ecology research, optimizing biotechnological applications, and contributing to environmental sustainability and public health strategies. MIMIC is designed for flexibility and ease of use, aiming to support researchers and practitioners in microbial ecology and microbiome research. This software package contributes to microbial ecology research and supports ecological predictions and applications, benefiting the scientific and applied microbiology communities. |
| Type Of Technology | Software |
| Year Produced | 2023 |
| Open Source License? | Yes |
| Impact | The software has been presented at two meetings. |
| URL | https://github.com/ucl-cssb/MIMIC |
| Description | RRI survey |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | As part of the responsible research and innovation (RRI) initiative, we launched a survey to assess current public attitudes towards microbiome engineering with a particular focus on healthcare applications. This work falls under the "Engage" component of the AREA (Anticipate, Reflect, Engage, Act) framework that EPSRC encourages researchers to follow (1). Our work could potentially have a therapeutic purpose for patients with colon cancer in the future, therefore success would be reliant on patients' acceptability towards engineered live bacterial therapeutic product (eLBP). This led us to design a survey to assess the attitudes towards microbiome engineering as a general principle and more specifically engineered live bacteria. |
| Year(s) Of Engagement Activity | 2022,2023 |