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

“威胁生命的真菌感染正在增加，脆弱的患者数量不断增加，耐药性的出现，特别是在烟曲霉的变种中。为了克服这个问题并开发新的治疗策略，我们必须了解曲霉菌如何在患者体内存活。人类的免疫系统部分通过破坏入侵病原体的DNA来对抗真菌感染，从而严重限制了微生物在宿主内的生存能力。曲霉利用ADP-核糖化作为协调对DNA损伤的反应和修复的关键信号。然而，建立ADP核糖化信号以响应DNA损伤的机制仍然不清楚。因此，这个项目的目的是描述一种关键蛋白质Af-PARP能够识别和响应DNA损伤的机制。负责DNA识别和修饰创建的Af-PARP不同区域之间的通信将由蛋白质的生化和结构分析确定。对这些过程的详细了解将有助于未来的药物开发。“

"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."