Research Area:Proteomics and ADP-ribosylation signaling
ADP-ribosylation (ADPr) is a key player in many physiological and disease conditions, including cancer, ageing and premature ageing syndromes.
We have recently discovered serine ADPr as a new type of histone mark. Shortly afterwards we were able to identify its ‘writers’ and ‘eraser’ and show that serine ADP-ribosylation (Ser-ADPr) is a widespread PTM that targets hundreds of different substrates, including many key proteins involved in genome stability maintenance. Our ground-breaking discovery of Ser-ADPr has immediately attracted much attention. In fact, the true scope and significance of this new PTM are even broader: we have shown in a just-published paper that Ser-ADPr is actually the primary form of ADPr in the DNA damage response. This long sought-after knowledge of the true modification sites is revolutionizing the research field. With this knowledge, attention is now shifting towards understanding the functional consequences and the detailed molecular mechanisms.
System-wide analysis of ADP-ribosylation sites
Our current findings make it clear that the attachment chemistry between serine residues and ADP-ribose, which we unexpectedly uncovered (Nat Chem Bio 2016), is one of the major types of ADPr. In this context we have shown that Ser-ADPr is a widespread PTM by identifying hundreds of different protein substrates that mediate processes important for genome stability (Mol Cell 2017). However, we hypothesize that its true significance and scope are much broader, and that Ser-ADPr is actually the primary form of ADPr in the DNA damage response. This is supported by our bioinformatic re-analyses of published proteomics datasets, which points to the existence of thousands of Ser-ADPr sites, implying that this type of ADPr is prevalent.
We plan to establish a “next generation” proteomics platform for in-depth ADPr site mapping. This approach will not only reveal the full scope of Ser-ADPr and the extent of its dependency on HPF1, but also elucidate the relative extent of the two PARP-1/-2 conjugation specificities (Mol Cell 2017); furthermore it will enable a variety of system-wide studies of Ser-ADPr and other types of ADPr in DNA repair signalling and beyond.
Excellent, ambitious and easy going.
Ability to join an interdisciplinary, collaborative and highly productive research environment and flexibility to operate in a fast-paced research filed. The candidate will receive extensive training (under the direct supervision of both the group leader and a senior postdoc) in the much sought-after proteomics technology, which will boosts his/her career within and beyond academia. This project gives also the opportunity of spending a short research period at Oxford University. The candidate will have the opportunity of publishing regularly in high profile journals as illustrated by our excellent publication rate over the last 2 years:
* Co-first authors
** Co-corresponding authors