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.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 01/10/2015 30/09/2023
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.
Exploitation Route The computational workflow can be used by others to study cell regulation in the context of different diseases, drugs, bacteria and different genetic backgrounds. We will apply the workflow to study how the regulation of Paneth cells is altered in the presence of Bifidobacteria.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://biorxiv.org/cgi/content/short/575845v1
 
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 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 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 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 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/