About the Project
The Babraham Institute is a world-leader in fundamental biological research investigating the systems that underpin development and healthy ageing. It is a recognised postgraduate University Partner Institute of the University of Cambridge. Starting October 2023 a Research Studentship will be available leading to a University of Cambridge PhD degree in the laboratory of Dr Peter Rugg-Gunn. This studentship can be awarded for up to 4 years.
Details of our interactive scientific programmes can be found on www.babraham.ac.uk. As a student at the Institute, you will have access to all of our outstanding science facilities, each one providing specialist equipment and expertise to support key research techniques and technologies.
Project Details
Background: Gene expression programmes are spatial-temporally controlled by cis-regulatory elements (CREs) including promoters and enhancers. Epigenomic information, such as DNA methylation, chromatin accessibility and various histone modifications, help to set the status of CREs in different cells and instruct lineage-specific gene regulatory networks (GRNs). However, our knowledge about how epigenomes contribute to establishing lineage-specific GRN is restricted by the limitation that bulk sequencing-based techniques capture epigenomes from tissues mixed with various cell types. The development of single cell epigenomic sequencing techniques, especially multi-omic methods that capture both transcriptomes together with epigenomes from the same single cell, will facilitate the unbiased definition of lineages and enable the examination of lineage-specific cis-regulatory networks. Towards this, our group has developed cutting-edge single cell multi-omics sequencing methods that profile transcriptomes and multiple histone modifications in the same single cells, providing powerful new tools to investigate lineage-specific epigenetic regulation with a wide range of applications.
Defining the epigenetic determinants that control the formation of different lineages in early human development remains an important goal with far-reaching basic and clinical implications. We study stem cell-derived integrated models of human embryos called blastoids, which have the remarkable capacity to specify the major cell lineages of the blastocyst. Because blastoids are genetically tractable and mimic key properties of early human embryos, they provide an important cell model to investigate developmental molecular mechanisms. These exciting models and our advanced single cell multi-omic methods are permitting deep insights into the epigenetic regulation of early human cell fate decisions.
Objectives: This project will apply single cell multi-omic sequencing methods to investigate the epigenetic pathways that contribute to lineage specification and progression in early human development. The project will begin by generating blastoids from human pluripotent stem cells, and will combine the blastoids with our newly developed in vitro implantation system to model early postimplantation development. To map the epigenetic and transcriptional changes that occur in cell lineages during blastoid implantation and development, you will use various sequencing methods such as CUT&Tag for bulk chromatin marks, CUT&RUN for TFs, ATAC-seq for chromatin accessibility, and our in-house single cell multi-omic sequencing methods, and will compare the data to human embryo data sets where available. There will also be the opportunity for you to contribute to the continued programme of method development. You will then test the hypothesis that epigenetic regulators act to reinforce lineage barriers by disrupting those regulators in human pluripotent stem cells during blastoid formation. Multi-omic sequencing, bioinformatic analyses and imaging approaches will characterise the associated phenotypes and mechanisms of lineage specification pathways.
The overall significance of this work will be to provide new and exciting insights into the gene regulatory principles that underpin cell fate decisions in human embryo development, with strong relevance for reproductive health and stem cell biology.
Training:
You will join the Rugg-Gunn lab within the Epigenetics Programme (8 groups, ~50 researchers), and a Graduate Programme of 30-40 highly motivated students. You will be fully trained in all techniques required for this project, in particular our advanced single cell multi-omic methods, sequencing methods such as CUT&Tag, CUT&RUN, ATAC-seq, human pluripotent stem cell culture and blastoid generation, genetic approaches including CRISPR/Cas9 gene editing, bioinformatics data analysis, and a broad range of routine and specialist molecular techniques, all supported by state-of-the-art facilities at Babraham.
We also anticipate that you will be able to work with early stage human embryos during the course of their project. Cambridge is a thriving environment for stem cell and developmental biology and we are well connected to this community through our affiliations with the Stem Cell Institute (www.stemcells.cam.ac.uk), the Centre for Trophoblast Research (https://www.trophoblast.cam.ac.uk), the Reproduction Strategic Research Initiative (https://www.repro.cam.ac.uk), the Human Developmental Biology Initiative (https://hdbi.org), and the Epigenetics Club.
For more details of our research, please see:
http://www.babraham.ac.uk/our-research/epigenetics/peter-rugg-gunn
Keywords: epigenetics, single cell biology; multi-omics; pluripotent stem cells; human blastoids; human embryos; cell fate decisions.
If you would like more information, or have any questions not answered on our website or the University of Cambridge Graduate Application Portal, please contact us:
The Graduate Studies Tutor, Babraham Hall, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT via email [Email Address Removed] .
An Equal opportunities employer. An Institute supported by the Biotechnology and Biological Sciences Research Council.
All applications for PhD Studentships at the Babraham Institute need to be made using the University of Cambridge Graduate Application Portal ( https://www.postgraduate.study.cam.ac.uk/application-process/applicant-portal-and-self-service-account ) regardless of funding source. Please see the “Applying for a PhD” pages on our website ( https://www.babraham.ac.uk/) for further details of the application process.
We hope to be able to invite short-listed applicants to attend our Institute for a series of interviews shortly after the application deadline. This will give applicants an opportunity to meet their Group Leader and their research group, as well as receiving a tour of our research facilities. Reasonable travel expenses will be paid to those invited.
Students will not be able to take up an award unless they meet all University eligibility criteria and are successful in securing admission to the University. In addition, they will not be able to apply for a visa (if needed) until they hold an unconditional offer from the University.
The deadline for submission of applications via the Graduate Application Portal is 1st December 2022. Incomplete applications will not be considered.
Find out more
Continue with Facebook
