1 PhD project offered in the IPP winter call 2020/2021
Ageing is commonly believed to start in adulthood. However, there is increasing evidence that organismic ageing begins already during embryonic development. For example, analyses of Down syndrome shows pronounced acceleration of ageing markers already in fetal stages, similar to adult tissues. This indicates that mechanisms of ageing might be productively studied during embryogenesis.
DNA repair plays a key role in preventing premature organismic ageing. We have recently shown that the DNA glycosylase NEIL1 is essential for early frog (Xenopus) development and in mouse embryonic stem cells (Han et al., 2019). Without NEIL1, frog embryos develop skull and tail malformations, due to p53 induction (see Figure 4). We found that NEILs protect embryonic cells from damaging oxygen derivatives and prevent accumulation of mitochondrial DNA lesions.
We now plan to study how this phenotype relates to ageing, where accumulation of mitochondrial DNA lesions plays a key role. Candidates will use frog embryosto characterize ageing and senescence in developing tissues. They will screen for novel epigenetic and DNA repair regulators, to understand the molecular network involved in these phenotypes. The successful candidate will have a strong background in Molecular or Developmental Biology to study ageing-related phenotypes in embryos. You will apply techniques including embryo culture, microinjection, RNA in situ hybridisation, confocal microscopy, Next Generation Sequencing and bioinformatics data analysis.
Publications relevant to the project
Han D, Schomacher L, Schüle KM, Mallick M, Musheev MU, Karaulanov E, Krebs L, von Seggern A, Niehrs C. (2019). NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress. eLIFE. 49044.