Identifying unique regulatory elements related to polymorphic imprinting and gestational aging in the placenta
Lead Research Organisation:
Earlham Institute
Department Name: Research Faculty
Abstract
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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.
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.
Organisations
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 |