Malaria Parasite Genomics, Development, Drug Resistance, Pathogenesis, and host-parasite interaction

在2019-2020年期间，我们利用约氏疟原虫/小鼠模型重点研究了疟疾发病的分子机制和信号转导途径。我们还有一个研究恶性疟原虫耐药机制的项目。 我们在几个项目上取得了良好的进展： 1.我们完成了一个多年的项目，剖析了约氏疟原虫红细胞结合样蛋白(PyEBL)在调节宿主对疟疾感染的先天反应中的机制。经过额外的实验和修订，这项工作最终发表在mBio上(mBio.2020，11：E02995-19)。 2.我们完成了另一个名为March1的基因研究项目，并在经过大量修改后发表在《中华儿科杂志》S A(2020年，DOI：10.1073/pnas.2006492117)上。这项工作表明，March1是一种重要的分子，在疟疾感染过程中可以调节宿主I型干扰素(IFN-I)的反应和T细胞的激活。此外，我们还建立并克隆了表达荧光素酶、MAVS和March1的细胞系，用于筛选小分子化合物抑制剂。 3.类似地，我们已经完成并发表了关于受体转运蛋白4(RTP4)的工作。我们发现RTP4在约氏疟原虫感染过程中可以调节宿主的干扰素-I反应。我们的工作还表明，RTP4在疟疾寄生虫和西尼罗河病毒感染期间的脑发病机制中发挥关键作用。这项研究最近再次发表在《中国科学学报》S A上(2020年，DOI：10.1073/pnas.2006492117)。 4.我们继续研究MMP3在疟疾感染中的功能。在一些约氏疟原虫的感染过程中，MMP3的表达高度上调。我们正在剖析MMP3在介导疟疾炎症中的机制。 5.我们一直在研究疟疾所致贫血的分子机制。我们已经证明，感染某些约氏疟原虫菌株会抑制红细胞(RBC)的成熟。我们正在进行最后几个实验，以完成出版手稿。 6.我们启动了一个项目，研究选择性嗅觉受体(ORs)在疟疾感染中的功能。我们已经确定了40个可能在约氏肺孢子虫感染中起作用的OR基因。 7.我们标记了几种恶性疟原虫E3泛素连接酶，结果表明，敲除某些基因会影响寄生虫对抗疟疾药物的反应。 8、与同事合作，我写了一篇关于疟原虫基因组学和遗传学的特邀综述，发表在《临床微生物评论》(2019年7月31日；32(4)上。PII：E00019-19。DOI：10.1128/CMR.00019-19)。

During the year of 2019-2020, we focused on studying the molecular mechanisms of malaria pathogenesis and signaling pathways using Plasmodium yoelii/mouse model. We also have a project studying mechanisms of drug resistance in Plasmodium falciparum. We have made good progresses in several projects: 1. We have completed a multi-year project dissecting the mechanism of Plasmodium yoelii erythrocyte binding-like protein (PyEBL) in regulating host innate response to malaria infections. This work was finally published in mBio after additional experiments and revision (mBio. 2020, 11:e02995-19). 2. We have finished another project studying a gene called March1 and published the work in Proc Natl Acad Sci U S A (2020, doi: 10.1073/pnas.2006492117) after extensive revision. This work shows MARCH1 is an important molecule that can regulate host type I interferon (IFN-I) response and T cell activation during malaria infections. Additionally, we have generated and cloned cell lines expressing luciferases, MAVS, and MARCH1 for screening small compound inhibitors. 3. Similarly, we have finished and published the work on receptor transporter protein 4 (RTP4). We show that RTP4 can regulate host IFN-I response during P. yoelii infections. Our work also suggests that RTP4 plays a critical role in brain pathogenesis during malaria parasite and West Nile virus infections. This work was again published in Proc Natl Acad Sci U S A recently (2020, doi: 10.1073/pnas.2006492117). 4. We continued to work on characterization of MMP3 function in malaria infections. MMP3 is highly up-regulated during infections of some P. yoelii strains. We are dissecting the mechanism of MMP3 in mediating inflammation in malaria. 5. We have been studying the molecular mechanism of malaria induced anemia. We have shown that infections with certain P. yoelii strains inhibit red blood cell (RBC) maturation. We are performing the last few experiments to complete a manuscript for publication. 6. We initiated a project investigating the functions of selected olfactory receptors (ORs) in malaria infections. We have identified 40 OR genes that may play a role in P. yoelii infections. 7. We have tagged several P. falciparum E3 ubiquitin ligases and showed that knocking-down some of the genes affects parasite responses to anti-malarial drugs. 8, Working with colleagues, I wrote an invited review on Plasmodium genomics and genetics that was published in Clin Microbiol Rev (2019 Jul 31;32(4). pii: e00019-19. doi: 10.1128/CMR.00019-19).