Jonathan Grimes教授是Diamond会员、牛津大学结构生物学副教授。他用Diamond来研究各种各样的病毒，尤其对“它们是如何复制的”很感兴趣。Grimes教授补充道：“聚合酶仅仅是复杂的病毒复制过程的一个组成部分。Diamond的研究设施，使我们能够在原子尺度上定位和可视化这些微小的生物过程。有了这些宝贵的信息，药学研究——无论是药物设计还是疫苗开发，都可以有更好的针对性。这方面的知识，是产生一种创新医疗方法和治疗方法的第一步。“更重要的是，这一发现也可能影响治疗类似病毒的药物开发。Grimes得出的结论是：“虽然病毒在其结构、作用和组件上有所不同，但是，就像其他物种一样，可以根据共有的特征而被分成几组。了解C型流感病毒的聚合酶如何构成和发挥功能，可以为同一家族其他病毒的聚合酶提供见解，包括更具侵略性和危险的A型和B型流感病毒。根据这些知识，我们还将研究狂犬病毒和埃博拉病毒的聚合酶，试图确定它们的确切结构，因此可以相同的方式，为上述疾病的治疗提供新的途径。”
参考阅读：
Nature. 2015 Oct 26. doi: 10.1038/nature15525
PMID: 26503046
Crystal structure of the RNA-dependent RNA polymerase from influenza C virus
Abstract： Negative-sense RNA viruses, such as influenza, encode large, multidomain RNA-dependent RNA polymerases that can both transcribe and replicate the viral RNA genome. In influenza virus, the polymerase (FluPol) is composed of three polypeptides: PB1, PB2 and PA/P3. PB1 houses the polymerase active site, whereas PB2 and PA/P3 contain, respectively, cap-binding and endonuclease domains required for transcription initiation by cap-snatching. Replication occurs through de novo initiation and involves a complementary RNA intermediate. Currently available structures of the influenza A and B virus polymerases include promoter RNA (the 5' and 3' termini of viral genome segments), showing FluPol in transcription pre-initiation states. Here we report the structure of apo-FluPol from an influenza C virus, solved by X-ray crystallography to 3.9 Å, revealing a new 'closed' conformation. The apo-FluPol forms a compact particle with PB1 at its centre, capped on one face by PB2 and clamped between the two globular domains of P3. Notably, this structure is radically different from those of promoter-bound FluPols. The endonuclease domain of P3 and the domains within the carboxy-terminal two-thirds of PB2 are completely rearranged. The cap-binding site is occluded by PB2, resulting in a conformation that is incompatible with transcription initiation. Thus, our structure captures FluPol in a closed, transcription pre-activation state. This reveals the conformation of newly made apo-FluPol in an infected cell, but may also apply to FluPol in the context of a non-transcribing ribonucleoprotein complex. Comparison of the apo-FluPol structure with those of promoter-bound FluPols allows us to propose a mechanism for FluPol activation. Our study demonstrates the remarkable flexibility of influenza virus RNA polymerase, and aids our understanding of the mechanisms controlling transcription and genome replication.