Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2022 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
This 4-year PhD studentship is offered in Dr John Diffley’s Group based at the Francis Crick Institute (the Crick).
Each time a human cell divides, it must make an exact copy of its 46 chromosomes. This requires precise duplication of ~6 billion base pairs of genomic DNA and all its associated proteins. Mistakes in this process can lead to developmental defects and cancer. Chromatin is packaged as nucleosomes comprising 147bp of DNA wrapped around a core of eight histone proteins. The nucleosome is a stable structure which must be disrupted each time the double helix is accessed during replication. ‘Epigenetic’ information in the form of covalent histone modifications must be re-established on both daughter strands immediately behind the replication fork. Inheritance of parental histones with their covalent marks must be coordinated with deposition of new histones into nucleosomes. And repressive heterochromatin must be replicated and immediately re-established after replication.
Our goal is to achieve a deep understanding of how DNA replication is coordinated with the disassembly and reassembly of chromatin to ensure accurate chromosome duplication.
We will use in vitro reconstitution of chromatin replication along with molecular genetics and structural biology to:
· Generate a molecular view of how the budding yeast replication machinery, with other key factors, disrupts parental nucleosomes during replication.
· Determine how parental nucleosomes are transferred to the nascent daughter strands.
· Understand how deposition of new histones is coordinated with the inheritance of parental histones.
· Characterise how budding yeast heterochromatin is disrupted and re-established during replication.
This work will underpin our long-term goal of reconstituting functional chromosomes from defined components to understand how DNA replication interacts with gene expression, DNA repair and chromosome segregation.
Candidate background
This project would suit candidates with a background in biochemistry and/or genetics and an interest in basic cell biology and molecular mechanisms.
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘INSTITUTION WEBSITE’ LINK ABOVE) BY 12:00 (NOON) 11 November 2021. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.