Controlling genome integrity: Regulation of the (ADP-ribosyl)transferase Af-Parp from Aspergillus fumigatus

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"Life-threatening fungal infections are on the rise with an increasing vulnerable patient population andthe appearance of drug resistance, especially in Aspergillus fumigatus variants. To overcome thisproblem and develop new treatment strategies, we must understand how Aspergillus can survive in apatient's body. The human immune system combats fungal infections partly by damaging the DNA ofthe invasive pathogen, thus severely restricting the microbe's ability to survive within the host.Aspergillus utilises ADP-ribosylation, a posttranslational modification, as a crucial signal to coordinatethe response to, and repair of, DNA damage. However, the mechanisms by which the ADP-ribosylationsignal is established in response to DNA damage remains elusive. Therefore, the aim of this project isto characterise the mechanisms by which a critical protein, Af-Parp, enables the recognition andresponse to DNA damage. The communication between different regions of Af-Parp, responsible forDNA recognition and modification creation, will be determined by biochemical and structural analysesof the protein. A detailed understanding of these processes will aid future drug development."