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

"Life-threatening fungal infections are on the rise with an increasing vulnerable patient population and
the appearance of drug resistance, especially in Aspergillus fumigatus variants. To overcome this
problem and develop new treatment strategies, we must understand how Aspergillus can survive in a
patient's body. The human immune system combats fungal infections partly by damaging the DNA of
the 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 coordinate
the response to, and repair of, DNA damage. However, the mechanisms by which the ADP-ribosylation
signal is established in response to DNA damage remains elusive. Therefore, the aim of this project is
to characterise the mechanisms by which a critical protein, Af-Parp, enables the recognition and
response to DNA damage. The communication between different regions of Af-Parp, responsible for
DNA recognition and modification creation, will be determined by biochemical and structural analyses
of the protein. A detailed understanding of these processes will aid future drug development."