Networking Bifidobacterium: integrating omics modelling and experimental validation to understand beneficial traits
Lead Research Organisation:
University of East Anglia
Department Name: Graduate Office
Abstract
Numerous animal and human studies have suggested that the presence of gut microbiota genus Bifidobacterium is associated with a range of health benefits, including protection against pathogens. This project focuses on understanding biology of Bifidobacterium by measuring gene expression and metabolites in bacteria under various conditions. Generated so called 'omics' datasets will be interpreted by looking at models of bacterial metabolism and gene regulation.
Molecular networks have proven useful in data integration and interpretation but rely on good quality resources that are often not available for less well-studied species. The main aim is to apply a comprehensive approach to study metabolic, signalling and regulatory networks by combining reconstruction of metabolic model with simulations of network steady states and multivariate statistics. The computational platform developed in this PhD project will provide the setting in which to disentangle the molecule specific interactions between strains and species that would be central to understand microbes and how they respond in the gut environment and thus impact human health.
Molecular networks have proven useful in data integration and interpretation but rely on good quality resources that are often not available for less well-studied species. The main aim is to apply a comprehensive approach to study metabolic, signalling and regulatory networks by combining reconstruction of metabolic model with simulations of network steady states and multivariate statistics. The computational platform developed in this PhD project will provide the setting in which to disentangle the molecule specific interactions between strains and species that would be central to understand microbes and how they respond in the gut environment and thus impact human health.
People |
ORCID iD |
| Tamas Korcsmaros (Primary Supervisor) | |
| Agatha Treveil (Student) |
Publications
Jones EJ
(2019)
Integrative analysis of Paneth cell proteomic and transcriptomic data from intestinal organoids reveals functional processes dependent on autophagy.
in Disease models & mechanisms
Treveil A
(2020)
Regulatory network analysis of Paneth cell and goblet cell enriched gut organoids using transcriptomics approaches.
in Molecular omics
Treveil A
(2021)
ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways.
in PLoS computational biology
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011216/1 | 01/10/2015 | 31/03/2024 | |||
| 1805508 | Studentship | BB/M011216/1 | 01/10/2016 | 30/09/2020 | Agatha Treveil |
| Description | - Bifidobacteria specific regulatory and signalling networks cannot reliably be inferred using computational techniques. More high throughput data is required. - Alongside others in the group, we developed a combined wet lab and computational workflow to study the regulatory pathways within cells lining the gut. The pipeline/workflow uses organoid cultures to grow the cells and technology called fluorescence activated cell sorting (FACS) to split the cultures by cell type. We then carry out sequencing on the cell types to obtain their RNA levels. This data is analysed (alongside other published information) using network biology techniques to generate cell type specific regulatory pathways/networks. - We applied the workflow to look at two types of cells in the gut, Paneth cells and goblet cells. Dysfunction of both of these cell types is associated diseases including inflammatory bowel disease. From this analysis we have generated cell type specific regulatory pathways and used them to predict major regulators of the cell types. - We applied the previously developed workflows to study the effect of Bifidobacterium on mice intestinal epithelium. - We applied similar techniques to study the effect of cytokines on colonic organoids, predicting key features and regulators of cytokine signalling. - We applied similar techniques to develop a publicly accessible pipeline, called ViralLink, for network analysis of RNAseq data from viral (incl. SARS-CoV-2) infected cells or models. This pipeline will help other researchers to quickly and easily apply bioinformatics approaches to their data, obtaining information about pathway and molecular regulation changes upon infection. |
| Exploitation Route | The computational workflows we have developed can be used by others to study cell regulation in the context of different diseases, drugs, bacteria and different genetic backgrounds. Moreover, the application of ViralLink SARS-CoV-2 data will enable collaborative and interdisciplinary research while aiding identification of key viral mechanisms and highlighting variation between different conditions such as different viral variants and different cell types. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| URL | https://github.com/korcsmarosgroup/ViralLink |
| Description | Cytokine network biology |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Network analysis of cytokine data. |
| Collaborator Contribution | Transcriptomics data for analysis; involvement in research leading to journal article. |
| Impact | Journal manuscript in preparation. Multi-disciplinary: bioinformatics, clinical research, wet lab research |
| Start Year | 2019 |
| Description | Cytokine network biology |
| Organisation | King's College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Network analysis of cytokine data. |
| Collaborator Contribution | Transcriptomics data for analysis; involvement in research leading to journal article. |
| Impact | Journal manuscript in preparation. Multi-disciplinary: bioinformatics, clinical research, wet lab research |
| Start Year | 2019 |
| Description | Professional internship placement: Norfolk County Council |
| Organisation | Norfolk County Council |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | My Doctoral Training Partnership funding includes 3 months of funding for an external internship. For my internship I joined the Data and Analytics teams at Norfolk County Council and helped them to implement an automated analysis pipeline as well as collate a report on a young peoples survey in Norfolk. |
| Collaborator Contribution | The County Council has provided me with training opportunities and helped to build my CV for future employment opportunities. |
| Impact | - I implement an automated analysis pipeline for the Data and Analytics team - I collated a report on a young peoples survey in Norfolk. |
| Start Year | 2018 |
| Title | ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways |
| Description | The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a cell-type specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis. The workflow is available on GitHub (https://github.com/korcsmarosgroup/ViralLink) in an easily accessible Python wrapper script, or as customisable modular R and Python scripts. |
| Type Of Technology | Software |
| Year Produced | 2020 |
| Open Source License? | Yes |
| Impact | ViralLink has been used to study the effect of SARS-CoV-2 infection on lung cells within the publication. Subsequently it is being used for an ongoing project relating to the effect of SARS-CoV-2 infection in the intestines. |
| URL | https://zenodo.org/record/4266585 |
| Title | ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways |
| Description | The SARS-CoV-2 pandemic of 2020 has mobilised scientists around the globe to research all aspects of the coronavirus virus and its infection. For fruitful and rapid investigation of viral pathomechanisms, a collaborative and interdisciplinary approach is required. Therefore, we have developed ViralLink: a systems biology workflow which reconstructs and analyses networks representing the effect of viruses on intracellular signalling. These networks trace the flow of signal from intracellular viral proteins through their human binding proteins and downstream signalling pathways, ending with transcription factors regulating genes differentially expressed upon viral exposure. In this way, the workflow provides a mechanistic insight from previously identified knowledge of virally infected cells. By default, the workflow is set up to analyse the intracellular effects of SARS-CoV-2, requiring only transcriptomics counts data as input from the user: thus, encouraging and enabling rapid multidisciplinary research. However, the wide-ranging applicability and modularity of the workflow facilitates customisation of viral context, a priori interactions and analysis methods. Through a case study of SARS-CoV-2 infected bronchial/tracheal epithelial cells, we evidence the functionality of the workflow and its ability to identify key pathways and proteins in the cellular response to infection. The application of ViralLink to different viral infections in a cell-type specific manner using different available transcriptomics datasets will uncover key mechanisms in viral pathogenesis. The workflow is available on GitHub (https://github.com/korcsmarosgroup/ViralLink) in an easily accessible Python wrapper script, or as customisable modular R and Python scripts. |
| Type Of Technology | Software |
| Year Produced | 2020 |
| Impact | ViralLink was used to analyse the effect of SARS-CoV-2 infection of lung cells within the publication. Subsequently ViralLink is being used for a project looking at the effect os SARS-CoV-2 infection of the intestines. |
| Description | 17-21 July 2017_2nd Interdisciplinary Signaling Workshop |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | In this interdisciplinary workshop advanced science was combined with informal summer activities to solve multi-disciplinary scientific questions, by bringing early career scientists together with more established researchers in a relaxing and beautiful location. Invited speakers presented talks on the topics of cell regulation, network modelling, genomics, systems biology, bioinformatics, structural biology, biochemistry, and cheminformatics. Then, selected talks from other participants will be followed by multi-disciplinary teamwork sessions in the afternoon, followed by cultural and social activities, such as medieval team building and handicraft activities in the Visegrad Castle. Poster sessions and plenty of informal opportunities allowed the participants to discuss complex and exciting questions as well as develop new collaborations. The renaissance surroundings of the venue nicely matched with the interdisciplinary nature of the workshop. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://signalingworkshop.org/ |
| Description | 24-25 April 2017_Multiscale analysis of host-microbe interactions in plants, animals and humans |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | The aim of this workshop was to bring together key experts and early-stage scientists working on host-microbe interactions, including pathogen infections, commensals and microbiome level studies, to share novel scientific ideas on the multiscale investigation of host-microbe interactions and to provide an exciting opportunity to establish and improve cross-disciplinary and UK-wide collaborations. After kick off with three keynote speakers on current challenges, the program provides structured study groups to discuss 1) novel methodological approaches; 2) potential future projects requiring participants from different disciplines; 3) the best ways to get funding for such multi-disciplinary projects. We facilitated these goals with short presentations and brainstorming opportunities in coordinated team works, and with panel discussion with representatives of key relevant funding agencies and charities. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.multiscalebiology.org.uk/events/event/multiscale-analysis-of-host-microbe-interactions/ |
| Description | Biology careers event at the Universtiy of East Anglia |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Undergraduate students |
| Results and Impact | The event is aimed at university students interested in careers in Biology or a related subject. I gave a talk and sat on a panel to discuss Bioinformatics and PhDs/academia as a career path. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Comparative analysis of Paneth cell and enteroendocrine cell transcriptomics: organoid and signalling network based approaches Research in progress talk at Quadram Institute. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Comparative analysis of Paneth cell and enteroendocrine cell transcriptomics: organoid and signalling network based approaches Research in progress talk at Quadram Institute. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Computational Systems Biology 2: Analysing and visualising networks |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Training for local PhD students: Computational Systems Biology 2: Analysing and visualising networks |
| Year(s) Of Engagement Activity | 2019 |
| Description | Cytokine responsive transcriptional networks in inflammatory bowel disease |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Oral presentation to ~50 scientists and clinicians at the 6th Young European Crohns and colitis organisation basic science program in Vienna, Austria. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.ecco-ibd.eu/discover-the-programme-2020/educational-programme-2020/6th-y-ecco-basic-scie... |
| Description | Earlham Institute open day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Discussions with variety of audiences about gut bacteria and probiotics. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlham.ac.uk/open-day-2019 |
| Description | Earlham Institute open day |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Talk to ~50 members of the public sparking questions and discussion about probiotics and a healthy gut microbiome. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlham.ac.uk/open-day-2019 |
| Description | Norwich Science Festival |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | With the Earlham Institute (EI), I helped man a stall containing hands on activities to teach the public about DNA and the work carried out at EI. Many people came away from the stall with an increased understanding of and interest in genomes and genomic research. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://norwichsciencefestival.co.uk/ |
| Description | Norwich Science Festival |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Earlham Institute Bee trail at the Norwich science festival |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://norwichsciencefestival.co.uk/about/norwich-science-festival-2019/ |
| Description | Organoid transcriptomics to study cell regulation Internal research presentation at the Earlham Institute |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Organoid transcriptomics to study cell regulation Internal research presentation at the Earlham Institute |
| Year(s) Of Engagement Activity | 2019 |
| Description | Poster presentation at 2nd Interdisciplinary signalling workshop |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Poster presentation titled "Pathway Analysis to Study the Effect of Bifidobacteria on Autophagy in the Intestine" at the 2nd Interdisciplinary Signaling Workshop 2017. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.earlham.ac.uk/2nd-interdisciplinary-signaling-workshop-isw |
| Description | Poster presentation at EMBO conference Modularity of signaling proteins and networks |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation titled "Identifying signalling pathways regulating antimicrobial peptide production in the gut using network biology and organoid transcriptomics Modularity of signaling proteins and networks" at the EMBO conference Modularity of signaling proteins and networks. |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://meetings.embo.org/event/18-modularity |
| Description | Poster presentation at Exploring Human Host-Microbiome Interactions in Health and Disease conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation titled "Investigating regulation of intestinal function by Bifidobacteria using network biology and organoid approaches" at the Exploring Human Host-Microbiome Interactions in Health and Disease conference 2017. |
| Year(s) Of Engagement Activity | 2017 |
| URL | https://coursesandconferences.wellcomegenomecampus.org/our-events/exploring-human-host-microbiome-in... |
| Description | Poster presentation at Microbes in Norwich 2019 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation titled "Investigating regulation of intestinal function by Bifidobacteria using network biology and organoid approaches" at the Microbes in Norwich 2019 event. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://microbesinnorwich.org |
| Description | Royal Society Summer Science Exhibition |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | Led by Dr Lindsay Hall, myself and colleagues brought a 'walk through gut' stand to the Royal Society Summer Science Exhibition. This was an interactive exhibition where myself and colleagues talked to (and visually showed) students and the public, from 2 to 90 years old, about gut microbiomes. Many visitors, students and public alike, were very interested in the topic and expressed an interest in learning more on it in the future. We felt we contributed to increased awareness of the impact of lifestyle factors and antibiotics on gut microbiomes. Lindsay spoke on local news about the exhibition. |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://royalsociety.org/science-events-and-lectures/2019/summer-science-exhibition/ |
| Description | Signalling Networks: From Data to Modelling |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Contributed to a training course run at the Earlham institute entitled 'Signalling Networks: From Data to Modelling'. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.earlham.ac.uk/signalling-networks-data-modelling |
| Description | The regulatory landscape of intestinal cells - investigating the transcriptional effect of autophagy impairment observed in Crohn's disease using organoid and network biology approaches 14th congress of European Crohn's and colitis organisation Copenhagen, Denmark |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Updating the Inflammatory Bowel Disease community about the regulatory landscape and the role of autophagy in various types of intestinal cells |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://academic.oup.com/ecco-jcc/article/13/Supplement_1/S031/5300677 |
| Description | The regulatory landscape of intestinal cells-investigating the transcriptional effect of autophagy impairment observed in Crohn's disease using organoid and network biology approaches in the 2019 Young European Crohns and Colitis Organisation basic science meeting |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk on the regulatory landscape of intestinal cells at the 2019 Young European Crohns and Colitis Organisation basic science meeting |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.ecco-ibd.eu/discover-the-programme-2019/educational-programme-2019/5th-y-ecco-basic-scie... |
| Description | ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Talk titled 'ViralLink: An integrated workflow to investigate the effect of SARS-CoV-2 on intracellular signalling and regulatory pathways' to attendees of the 5th Disease Maps Community Meeting |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://zenodo.org/record/4266585 |
| Description | Women of the Future |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Women of the Future encourages and engages young school age women to be successful in business and careers. The event held at the Norwich Research Park showcases the science across the park to encourage participation in STEM. I presented a poster of my research to the girls and their teachers. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://womenofthefuture.co.uk/ |