Broichhagen Johannes, Kilian Nicole
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Roessle-Strasse 10, 13125, Berlin, Germany.
Centre for Infectious Diseases, Parasitology, Heidelberg University Hospital, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany.
Chembiochem. 2021 Jul 1;22(13):2219-2236. doi: 10.1002/cbic.202000882. Epub 2021 Mar 31.
Parasitic diseases like malaria tropica have been shaping human evolution and history since the beginning of mankind. After infection, the response of the human host ranges from asymptomatic to severe and may culminate in death. Therefore, proper examination of the parasite's biology is pivotal to deciphering unique molecular, biochemical and cell biological processes, which in turn ensure the identification of treatment strategies, such as potent drug targets and vaccine candidates. However, implementing molecular biology methods for genetic manipulation proves to be difficult for many parasite model organisms. The development of fast and straightforward applicable alternatives, for instance small-molecule probes from the field of chemical biology, is essential. In this review, we will recapitulate the highlights of previous molecular and chemical biology approaches that have already created insight and understanding of the malaria parasite Plasmodium falciparum. We discuss current developments from the field of chemical biology and explore how their application could advance research into this parasite in the future. We anticipate that the described approaches will help to close knowledge gaps in the biology of P. falciparum and we hope that researchers will be inspired to use these methods to gain knowledge - with the aim of ending this devastating disease.
自人类诞生之初,诸如热带疟疾之类的寄生虫病就一直在塑造着人类的进化与历史。感染后,人类宿主的反应从无症状到严重,甚至可能导致死亡。因此,对寄生虫生物学进行恰当研究对于解读独特的分子、生化及细胞生物学过程至关重要,而这些过程反过来又有助于确定治疗策略,比如有效的药物靶点和候选疫苗。然而,对许多寄生虫模式生物而言,实施用于基因操作的分子生物学方法颇具难度。开发快速且易于应用的替代方法,例如化学生物学领域的小分子探针,至关重要。在本综述中,我们将概述先前分子生物学和化学生物学方法的要点,这些方法已为深入了解恶性疟原虫提供了见解。我们将讨论化学生物学领域的当前进展,并探讨其应用在未来如何推动对这种寄生虫的研究。我们预计,所描述的方法将有助于填补恶性疟原虫生物学方面的知识空白,并且希望研究人员能受到启发,运用这些方法来获取知识,以期终结这种毁灭性疾病。