The laboratory of Helle Ulrich studies the regulatory mechanisms that ensure the complete and accurate duplication of a cell’s genetic information in every cell cycle, especially in the face of DNA damage. Our work in budding yeast has revealed that most lesions in the replication template are processed behind replication forks in dedicated sub-nuclear regions. However, we still do not understand how the choice between alternative damage bypass pathways is reached. Given the greater complexity of their signalling pathways, mammalian cells present an even larger variety of regulatory features that control how damaged DNA is replicated. Our lab is investigating these questions in both yeast and mammalian systems by focusing on regulatory factors at the interface of DNA replication and repair, particularly those linked to posttranslational protein modifications such as ubiquitin and SUMO.
Depending on the candidate’s preferences, projects are available to investigate DNA damage bypass and repair mechanisms in human cells or budding yeast. The research will involve standard approaches in Molecular and Cellular Biology, such as the analysis and manipulation of protein abundance, interactions, modifications and subcellular localization. Methods like fluorescence microscopy, flow cytometry and genome editing by CRISPR/Cas9, but also more specialized assays such as chromatin immunoprecipitation, replication analysis by DNA combing or the genome-wide mapping of lesions by next-generation sequencing are established in the lab. Projects may address the impact of chromatin dynamics on the replication of damaged DNA, the contributions of newly identified factors to damage processing pathways, the mechanisms of replication fork reversal and restart in response to different types of replication stress or the consequences of ubiquitin and/or SUMO modification of key regulators. Motivated candidates with a good background in molecular biology, particularly in DNA replication or repair, are encouraged to apply.
Tagged as: Life Sciences
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