Helle Ulrich

Research in the Ulrich lab centres on the intersection between two primary hallmarks of ageing: genomic instability and loss of proteostasis. Whereas genome maintenance mechanisms preserve the genetic information of an organism by preventing or repairing DNA damage and assuring faithful duplication of the genome, protein quality control systems regulate the abundance of the cell’s major building blocks and safeguard their functionality. Members of the ubiquitin family play an important role in proteostasis as they control protein function, abundance and localisation. Thus, like defects in DNA repair pathways, deregulation of ubiquitin signalling is associated with many age-related diseases.

The Ulrich lab investigates the contributions of ubiquitin and the ubiquitin-like protein SUMO to the regulation of DNA replication, repair and genome stability, focusing on a pathway of DNA damage bypass that allows genome replication in the presence of DNA-damaging agents. This pathway helps cells resist genotoxic agents, but also has the potential to cause genome instability and must be tightly regulated. The lab uses a combination of genetic, genomic, molecular biological and biochemical approaches to elucidate how the ubiquitylation or SUMOylation of key replication factors regulates the replication of damaged DNA and how this is coordinated with the overall cellular DNA damage response. We have developed next generation sequencing methods for genome-wide mapping of DNA lesions and replication intermediates and are designing experimental tools to detect, manipulate or inhibit ubiquitylation and SUMOylation reactions within cells.

Research website