Identifying unique regulatory elements related to polymorphic imprinting and gestational aging in the placenta

Lead Research Organisation: Earlham Institute
Department Name: Research Faculty

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

In this application we propose a series of experiments to better understand the hierarchical placental epigenome across gestation (by assessing two different developmental time points) to determine intra-sample variability and to gain widespread functional insights of potential cis-acting regulatory elements with unique placenta profiles. The data will be generated and assessed in a genome-wide unbiased fashion, allowing us to monitor gestational-dynamics in imprinted gene expression and identify cis-regulatory usage that would account for the widespread down-regulation of expression previously reported.

There is an inter-relationship between DNA methylation and additional layers of epigenetic information essential for genome function. We have previously shown that the placenta is uniquely hypomethylated and that this methylation is dynamic through pregnancy. However, addition epigenetic tiers have largely been uncharacterised in this essential tissue and mechanisms responsible for the global increase in methylation (on the unique hypomethylated background) are unknown. Fascinatingly, transcriptional down-regulation associated with imprinted transcripts at term is independent of methylation, since all imprinted differentially methylated regions maintain faithful allelic profiles, suggesting other epigenetic mechanisms must be responsible.

Main deliverables: (1) We will produced consensus epigenetic maps for early and late placenta samples. Through exploitation of these datasets, we will ultimately identify functional regulatory elements, many of which we anticipate will change during gestation. (2) By performing bioinformatic analyses using trio-SNP information to discriminate alleles, the temporal epigenetic and expression profiles for imprinted genes will be revealed. Since the epigenetic datasets will be produced in an unbiased genome-wide fashion, this will allow novel cis-regulatory elements to be defined and functionally characterised.

Publications

10 25 50
 
Description Festival of Genomics 2024 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The Earlham Institute exhibited at the Festival of Genomics and Biodata in London - an event attended by around 5,000 people. Complemented by talks and panel discussions delivered by our researchers, our stand provided an opportunity to showcase our science, technology platforms, and opportunities for engagement. EI delegates collectively had more than 100 conversations about the Institute, ranging from interest in jobs or PhDs to requests for scientific services. The true impact of attendance will be felt over the long-term, with a few potential collaboration opportunities being explored.
Year(s) Of Engagement Activity 2024
URL https://festivalofgenomics.com/london/en/page/home
 
Description Hosting week-long work experience placement student 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A week on placement work, supervising a student in bioinformatics and life working at the institute. This involved preparation of materials, arranging visits with computing facilities, lab tours, a work package and contact time, including both in person and virtual.
Year(s) Of Engagement Activity 2023
 
Description Industry Seminar Babraham Institute 10/10/2023 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact The day was made up of a networking brunch for BI visitors & a selection of EI colleagues. This was followed with a discussion around best practice for working with industry. This was followed with 2 workshops on the following topics, Budget, pricing and project management, Building skillset for working with industry among technical staff, Inter-institute projects and services
(blue sky), Training and staff exchanges & then a whole group discussion to summarize the workshops. There was a networking lunch for students with BI then delivered a 60 minute seminar which was open to all colleagues at EI. The day lead to building new relationships & looking at good practices and Knowledge Exchange.
Year(s) Of Engagement Activity 2023
 
Description Invited seminar - Stockholm - What Your Are Missing Matters - Characterisation of novel splicing events across brain tissues and during development 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at a Oxford Nanopore Technology Event
Year(s) Of Engagement Activity 2024
URL https://nanoporetech.com/about/events/nanopore-days/nanopore-day-stockholm-2024#event-overview
 
Description Outreach talk (Langwith Bassett Garden Club) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact An evening presentation and open discussion with a community hobby group (gardening club) about single-cell biology, and the work of our group and Institute. This was a 45-min presentation followed by Q&A and open discussion around the role of single-cell biology techniques in health and disease, envionmental protection, food security and gave a diverse and demographically wide-ranging audience an opportunity to find out more about what science we are doing and how this can help them, and society in general.
Year(s) Of Engagement Activity 2024
 
Description Presentation - Festival of Genomics 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact ~100 attendees at the Festival of Genomics were present for my talk on Single-cell long read sequencing
Year(s) Of Engagement Activity 2023
 
Description Single-cell show and tell 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact We organized the single-cell show and tell to showcase our equipment in the single-cell laboratories, talk about our workflows and provide some hands on lab experience to our colleagues within EI. We had 38 participants with different scientific and non-scientific backgrounds. The feedback was very positive, and most people would like to see other groups organize similar events.
Year(s) Of Engagement Activity 2023
 
Description Single-cell show-and-tell: Activity based tours of the EI single-cell labs 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact 40 staff from EI were given an interactive tour of the single-cell labs. We introduced them to the different platforms and concepts behind single-cell analysis. We hosted staff from operations, communications, business development and faculty, all staff at EI were invited. The event stimulated questions and discussion about both the biology and technology associated with single cell work.
Year(s) Of Engagement Activity 2023
 
Description Speed-networking (Sir Isaac Newton Sixth Form) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A full day of rotation speed-networking where sixth form students are given the opportunity to engage with industry specialists across a range of informatic related careers. My role here was showcasing the role of a bioinformatician and the work of the institute. This was attended by all students at the sixth form college who are undertaking IT qualifications and thinking about university and career options.
Year(s) Of Engagement Activity 2022,2023
 
Description Visit from NNUH clinicians to the Earlham Institute on 19 June 2023 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact BDI team and IM of the Earlham Institute organised the visit from NNUH clinicians to the Earlham Institute. We held a workshop for researchers and clinicians to discuss their interests in developing potential collaborative projects that would utilise earlham expertise and capabilities and NNUH access to patients and patient data, and to the Norwich Biorepository.
Year(s) Of Engagement Activity 2023