杰出青年科学基金获得者

　　1999         中国农业大学，博士

　　1999 - 2000  加州大学（戴维斯），博士后

　　2001 - 2006  佛罗里达州立大学生物系，博士后

　　2007 - 至今  中国科学院生物物理研究所，研究员

　　2007 - 至今  中国细胞生物学会，会员

　　2007 - 至今  中国生物物理学会，会员

　　2000 - 至今  美国细胞生物学会 (ASCB)，会员

　　2004 - 至今  美国科学促进会 (AAAS），会员

　　精子发生过程中，精子细胞变形成为精子，精子向卵子运动并与卵细胞融合实现遗传物质的传递。这一过程涉及细胞极性建立、细胞定向运动等生物学现象。本研究组结合线虫Ascaris suum和Caenorhabditis elegans的优势，利用生物化学、细胞生物学、遗传学、生物电镜等方法研究精子变形、精子运动的分子机理。同时，我们集中研究既是精子运动骨架又是胞外信号分子的精子主要蛋白 MSP发挥双重功能的分子机理，以及MSP同源蛋白质在人类神经退行性疾病——肌萎缩性侧索硬化症中发挥功能的可能机理。

主要研究内容包括：

1. 线虫精子变形的分子机制

Ascaris suum雄虫精子细胞必须经过激活变形后才能成为可运动的、具功能的精子。Ascaris suum精子激活是胞外信号分子介导的细胞记性建立的过程。Ascaris suum雄虫输卵管末端匀浆液，体外可启动精子变形。通过分级分离，我们寻找匀浆液中的活性因子，并研究该激活因子的靶分子，进而阐明活性因子及其靶分子参与的信号调控通路；

　　线虫精子激活过程是在胞外信号分子的作用下，精子细胞内来源于高尔基体和内质网的细胞器MO与精子细胞质膜融合完成细胞内囊泡运输和细胞胞吐，我们对这一过程涉及的信号转导同样很感兴趣。

2. 线虫精子运动机理研究

　　与哺乳动物精子的鞭毛运动不同，线虫精子的运动行为与以肌动蛋白(actin)为基础的阿米巴变形运动相似。但是，在线虫精子中没有肌动蛋白，取而代之的是以精子主要蛋白(major sperm protein, MSP)装配的胞质骨架驱动的细胞运动。相比其他阿米巴样运动细胞，结构简单、高度特化的线虫精子更有助于研究阿米巴样细胞运动的基本机制，是研究以MSP为基础的细胞运动的理想材料。通过电子显微技术，生物化学和细胞生物学方法，我们研究线虫精子MSP胞质骨架的装配模式，并揭示调控 MSP胞质骨架动态变化的信号通路。

　　MSP不仅是线虫精子伪足骨架的分子基础，而且还是实现精卵信号通讯的胞外信号分子，促进卵细胞成熟和排卵。人类MSP的同源蛋白VAPB同样具有信号分子的功能。VAPB突变可引起神经退行性疾病——肌萎缩性侧索硬化(amyotropic lateral sclerosis, ALS)。MSP及含MSP结构域的信号分子在线虫、哺乳动物中的生物学功能，也是我们的研究重点。我们利用C. elegans作为模式生物研究作为信号分子的MSP如何实现胞外运输，完成信号通讯。

3.C. elegans遗传学

C.elegans作为模式生物，有遗传学上的优势。通过正向遗传学和反向遗传学方法，筛选参与精子变形、精子运动和精卵识别的关键基因。结合C.elegans的遗传学优势和Ascaris suum的生物化学优势，十分有利于我们在细胞极性建立、细胞运动方面的研究。

1. Deng H, Qiao X, Xie T, Fu W, Zhao Y, Guo M,Miao L, Chen C, Shen K and Wang X. (2021) SLC-30A9 is required for Zn²⁺homeostasis, Zn²⁺mobilization, and mitochondrial health.PNAS. 118(35): e2023909118 DOI:10.1073/pnas.2023909118

2. Wang Q, Cao Z, Du B, Zhang Q, Chen L, Wang X, Yuan Z, Wang P, He R, Shan J, Zhao Y,Miao L. (2021) Membrane contact site-dependent cholesterol transport regulates Na⁺/K⁺-ATPase polarization and spermiogenesis inCaenorhabditis elegans.Dev Cell.  56:1631-1645 doi: 10.1016/j.devcel.2021.05.002.

3. Du P, Wang J, He Y, Zhang S, Hu B, Xue X,Miao L, and Ren H. (2021) AtFH14 crosslinks actin filaments and microtubules in different manners.Biol Cell. 113(5):235-249

4. Zhao Y, Tan CH, Krauchunas A, Scharf A, Dietrich N, Warnhoff K, Yuan Z, Druzhinina M, Gu SG,Miao L, Singson A, Ellis RE, Kornfeld K. (2018) The zinc transporter ZIPT-7.1 regulates sperm activation in nematodes.PLoS Biol. 16(6):e2005069.

5. Zhu H, Chen L, Yang Y, Zhu Z, Zhang X, Li W,Miao L, Zhang Y, Ou G. (2016) The glial actin cytoskeleton regulates neuronal ciliogenesis.Cell Res[Epub ahead of print]. doi: 10.1038/cr.2016.131

6. Li Y, Chen B, Zou Z, Wang X, Wu Y, Zhao D, Sun Y, Liu Y, Chen L,Miao L, Yang C and Wang X. (2016) Lysosomal integral membrane protein SCAV-3 maintains lysosome integrity and normal adult lifespan inC. elegans.JCB215(2):167-185.

7. Li Y, Xu M, Ding X, Yan C, Song Z, Chen L, Huang X, Wang X, Jian Y, Tang G, Tang C, Di Y, Mu S, Liu X, Liu K, Li T, Wang Y,Miao L, Guo W, Hao X, and Yang C. (2016) Protein kinase C controls lysosome biogenesis independently of mTORC1.Nat Cell Biol18:1065-1077.

8. Li R, Ren X, Bi Y, Ho VW, Hsieh CL, Young A, Zhang Z, Lin T, Zhao Y,Miao L, Sarkies P, Zhao Z. (2016) Specific down-regulation of spermatogenesis genes targeted by 22G RNAs in hybrid sterile males associated with an X-Chromosome introgression.Genome Res.9:1219-1932.

9. Wang Y, Zhang Y, Chen L, Liang Q, Yin XM,Miao L, Kang BH, Xue D. (2016) Kinetics and specificity of paternal mitochondrial elimination inCaenorhabditis elegans.Nat Commun.7:12569.

10.Miao Land L'Hernault SW. (2014) Role of posttranslational modifications inC. elegansandAscarisspermatogenesis and sperm function. In: Posttranslational Protein Modifications in the Reproductive System, edited by Peter Sutovsky.Springer Science+Business Media, LLC.

11. Ma X, Zhu Y, Li C, Huang P, Cao Z, Liu Z, Zhao Y, Xue P, Chen S, Yang F,Miao L. (2014) Characterization ofCaenorhabditis eleganssperm mRNAome.BMC Genomics15:168.

12. Liu Z, Wang B, He R, Zhao Y,Miao L. (2014) Calcium signaling and the MAPK cascade are required for sperm activation inCaenorhabditis elegans.Biochim Biophys Acta. 1843:299-308.

13. Shang Y, Chen L, Liu Z, Ma X,Miao L. (2013) Cytosolic Ca²⁺as a multifunctional modulator is required for spermiogenesis and motility acquisition inAscaris suum.Protein & Cell4:456-466.

14. Chen D, Jian Y, Liu X, Zhang Y, Liang J, Qi X, Du H, Zou W, Chen L, Chai Y, Ou G,Miao L, Wang Y, and Yang C. (2013). Clathrin and AP2 are required for phagocytic receptor-mediated apoptotic cell clearance inCaenorhabditis elegans.PLoS Genetics9(5), e1003517.

15. Liu Z, Chen L, Shang Y, Huang P,Miao L. (2013) The micronutrient element zinc modulates sperm activation through the SPE-8 pathway inCaenorhabditis elegans.Development140: 2103-2107.

16. Huang P, Ma X, Zhao Y,Miao L. (2013) TheC. eleganshomolog of RBBP6 (RBPL-1) regulates fertility through controlling cell proliferation in the germline and nutrient synthesis in the intestine.PLoS ONE8(3): e58736.

17. Ma X, Zhao Y, Sun W, Shimabukuro K,Miao L. (2012) Transformation: how do nematode sperm become activated and crawl?Protein & Cell10:755-761.

18. Dou J, Chen L, Hu Y,Miao L. (2012) Cholesterol and the biosynthesis of glycosphingolipids are required for sperm activation inCaenorhabditis elegans.Biochim Biophys Acta1821:934-942.

18. Zhao Y, Sun W, Zhang P, Chi H, Zhang M, Song C, Ma X, Shang Y, Wang B, Hu Y, Hao Z, Hühmer A, Meng, F, L'Hernault S, He S, Dong M,Miao L. (2012) Nematode sperm maturation triggered by protease involves sperm-secreted serine protease inhibitor (Serpin).PNAS109: 1542–1547.

20. Ma X, Zhu Y, Li C, Shang Y, Meng F, Chen S,Miao L. (2011) Comparative transcriptome sequencing of Germline and Somatic Tissues of the Ascaris suum Gonad.BMC Genomics12:481.

21. Su S, Liu Z, Chen C, Zhang Y, Wang X, Zhu L,Miao L, Wang X, Yuan M. (2010) Cucumber Mosaic Virus Movement Protein Severs Actin Filaments to Increase the Plasmodesmal Size Exclusion Limit in Tobacco.The Plant Cell22:1161-1173.

22. Chen D, Xiao D, Zhang K, Wang B, Gao Z, Jian Y, Qi X, Sun J,Miao L, Yang C. (2010) Retromer Sorting Complex Regulates Apoptotic Cell Clearance by Phagocytic Receptor Recycling.Science327: 1261-1264.

23. Zhang Y, Yan L, Zhou Z, Yang P, Tian E, Zhang K, Zhao Y, Li Z, Song B, Han J,Miao L, Zhang H. (2009) SEPA-1 Mediates the Specific Recognition and Degradation of P Granule Components by Autophagy inC. elegans.Cell136: 308–321.

24.Miao L, Vanderlinde O, Liu J, Grant RP., Wouterse A, Philipse A, Stewart M, Roberts TM. (2008) The role of filament packing dynamics in powering amoeboid cell motility.PNAS105: 5390-5395.

25. Wang B, Liu Z,Miao L. (2008) Recent Advances in the study of spermatogenesis and fertilization inCaenorhabditis elegans,Hereditas(Beijing) 30:677-686 (invited review in Chinese).

26.Miao L. (2007) Recent progresses on the cellular motility, cell migration and cytoskeleton.Acta Biophysica Sinica. 23:281-289 (invited review in Chinese).

27.Miao L, Yi K, Mackey JM, Roberts TM. (2007) Reconstitution in vitro of MSP-based filopodium extension in nematode sperm.Cell Motility and Cytoskeleton. 64:235-247.

28. Wolgemuth C,Miao L, Vanderlinde O, Roberts TM, Oster G (2005) MSP dynamics drives nematode sperm locomotion.Biophysical Journal88: 2462-2471.

29. Meng FX,Miao L, Zhang SQ, Lou CH (2004) Ca²⁺is involved in muscarine-acetylcholine-receptor-mediated acetylcholine signal transduction in guard cells ofVicia fabaL.Chinese ScienceBulletin 49:471-475.

30.Miao L, Vanderlinde O, Stewart M, Roberts TM (2003) Retraction in amoeboid cell motility powered by cytoskeletal dynamics.Science302: 1405-1407.

31. Provencher LM,Miao L, Sinha N, and Lucas WJ (2001)Sucrose export defective1encodes a novel protein implicated in chloroplast to nucleus signaling.The Plant Cell13:1127-1141.

32. Meng FX,Miao L, Leng Q, Zhang SQ (2001) Incubation of Fluo-3 AM for measuring cytosolic Ca²⁺in guard cells ofVicia faba.Plant Physiology Communications37: 429-432 (in Chinese).

33.Miao L, Wang XC, Zhang WC (1999) The symplasmic connection of root cap inZea maysand its response to the external signal.Chinese Bulletin of Botany16: 42-44 (in Chinese).

34.Miao L, Wang XC, Zhang WC (1997) Osmotic stress decreases the activity of ATPase associated with plasmodesmata in root cap inZea mays.Acta Botanic Sinica39: 774-777.

（资料来源：苗龙研究员，2021-10-13）