Postdoc Fellow - ADP-ribosylation by PARP proteins in chromatin regulation, AstraZeneca, UK

PARP's other life: the role of ADP-ribosylation in chromatin regulation from a biophysical perspective

The Poly-ADP ribose polymerase (PARP) family of proteins are well known enzymes in the DNA damage repair pathway (DDR); PARP proteins also play an important role in maintaining chromatin architecture and facilitating gene transcription in the absence of DNA damage. PARPs directly interact with DNA breaks but it is not known how they are targeted to sites of de novo transcriptional activation. You’ll be part of a project that aims to investigate the structure and function of the PARP ADP-ribosylases with respect to their interactions with the nucleosome.


You’ll initially focus on producing recombinant PARP proteins and nucleosomes, the latter bearing histone modification mimics. You’ll map the interaction interface between PARP and nucleosomes via biomolecular NMR and in parallel the structure of the complex will be pursued by cryo-electron microscopy.


Carrying out biophysical and enzymatic characterisation of the nucleosome:PARP complexes will be part of the role. In order to demonstrate the relationship between PARP proteins and relevant nucleosome modifications in cells, it might be possible to extend the project to include RT-PCR or ChIP-Seq, depending on your expertise.


Structural studies will involve collaborating with the group of Dr Steve Gamblin based at The Francis Crick Institute. The Gamblin group has a long history of working on chromatin remodelling complexes and offer both invaluable scientific input and access to state of the art facilities at their London laboratories.


You’ll initially be based at Alderley Park in Cheshire until completion of our new facilities in Cambridge. Alderley Park houses the AZ UK biomolecular NMR group (two 600 and one 800 cryoprobe equipped spectrometers) and the RAD protein reagents group. These groups will give you access to considerable expertise and equipment, while your research will give you the opportunity to influence fellow scientists across many disciplines.


 Please apply using the link below: