张文华-澳门银银河官方网

our laboratory studies the biosynthesis and cellular roles of trna n⁶-threonylcarbamoyladenosine (t⁶a), which is a necessary post-transcriptional modification universally found in ann-decoding trnas in the three domains of life. the t⁶a is located 3'-adjacent to the anticodon triplet in the anticodon stem loop of trnas, wherein it plays pivotal roles in preventing the u₃₃ and a₃₇ from unwanted watson-crick pairing as well as in enhancing the base pairing between anticodon triplet from trna and codon triplet from mrna. the absence or interfered making of trna t⁶a gravely affects cellular proteostasis and causes cell death, is also implicated in the growth and development of higher eukaryotes, and a set of human diseases, i.e. galloway-mowat syndrome. 

the two last universal common ancestor (luca) families tsac/sua5 and tsad/kae1/qri7 form a minimal duet to catalyze the substrates of l-threonine, bicarbonate, atp and trna to make trna t⁶a, during which a short-lived intermediate l-threonylcarbamoyladenylate (tc-amp) is necessarily generated to couple the chemical transformations. however, the molecular mechanisms and machinery workings underlying trna t⁶a biosynthesis might vary among different life systems, as additional organism-specific enzymes are needed for the enzymatic reconstitution of trna t⁶a. the enzymes function in ensemble, namely protein complex, either stable or dynamic. intriguingly, the kae1-mediated pentameric or octameric keops complex and tsad-mediated ternary tsad-b-e complex may also possess other important molecular functions apart from the crystal-clear one in catalyzing the trna t⁶a biosynthesis, such as keops' role promoting telomere elongation in yeast. 

we have aggregated ample knowledge and sophisticated techniques in dissecting the structure–activity relationship of trna t⁶a-modifying enzymes over the past decade. our lab people are doggedly focused on analyzing the structure-function relationship of these ancient luca enzymes, and on elucidating the sequential assembly and regulatory layers of the trna t⁶a biosynthetic machinery as well. furthermore, we are exploring the possible novel functions of keops complex and the cellular implications of trna t⁶a and other important t⁶a derivative modifications (i.e. ht⁶a, m⁶t⁶a, ms²t⁶a, ct⁶a, ms²ct⁶a) pathway by applying an array of approaches and techniques in molecular biology, enzymology, structural biology, cellular biology and genetics.

• 细胞活动与逆境适应教育部重点实验室开放课题基金（2021），主持；
• 中央高校优秀青年教师科研创新基金（2021-2022），主持；
• 中央高校基本科研业务费学科交叉创新团队（2021-2023），参与；
• 国家自然科学基金青年项目（2021-2023），主持；
• 甘肃省自然科学基金面上项目（2021-2022），主持；
• 中央高校优秀青年教师科研创新基金（2019-2020），主持；
• 姚高民生命科学基金（2018-2019），主持；
• 兰州大学人才引进科研基金（2018-2021），主持。

教育部高校青年教师国情教育研修班（第一期）优秀学员。

 本科生课程： 

《生物化学与分子生物学》（课程负责人）

兰州大学药学院

《生物化学》、《酶工程》（课程负责人）、《生物物理学》

兰州大学生命科学学院

研究生课程

《practical introduction to structural study of macromolecules》（课程负责人）、《结构生物学导论》

兰州大学生命科学学院英文课程

1. wang, j., zhou, j., mao, x., zhou, l., chen, m., zhang, w., wang, e. and zhou, x. (2022) commonality and diversity in trna substrate recognition in t6a biogenesis by eukaryotic keopss, nucleic acids res., 50, 2223–2239.
2. galicia, c., lhospice, s., varela, p., trapani, s., zhang, w., navaza, j., herrou, j., mignot, t. and cherfils, j. (2019) mgla functions as a three-state gtpase to control movement reversals of myxococcus xanthus. nature communications, 10, 5300.
3. das, s., malaby, a., nawrotek, a., zhang,w., zeghouf, m., maslen, s., skehel, m., chakravarthy, s., irving, t., bilsel, o., cherfils j. and lambright, d. (2019) structural organization and dynamics of homodimeric cytohesin family arf gtpase exchange factors in solution and on membranes. structure, 27, 1782–1797.
4. missoury, s., plancqueel, s., gallay, i., zhang, w., liger, d., durand, d., dammak, r., collinet, b. and van tilbeurgh, h. (2018) the crystal structure of the bacterial tsab/tsad/tsae complex responsible for the essential t⁶a trna-modification. nucleic acids res., 46, 5850-5860.
5. pichard-kostuch a.*, zhang, w.*,  liger, d., daugeron, m., letoquart, j.,  gallay, i.,  forterre, p., collinet, b.,  van tilbeurgh, h., basta, t. (2018) structure-function analysis of sua5 protein reveals novel functional motifs required for the biosynthesis of the universal trna t⁶a. rna, 24, 926-938.
6. ferrandez, y.*, zhang, w.*, peuroi, f., akendengué, l., blangy, a., zeghouf, m. and cherfils, j. (2017) allosteric inhibition of the guanine nucleotide exchange factor dock5 by a small molecule. scientific reports, 7:14409| doi:10.1038/s41598-017-13619-2|1-13.
7. zhang, w., collinet, b., perrochia, l., durand, d. and van tilbeurgh, h. (2015) the atp-mediated formation of the ygjd-yeaz-yjee complex is required for the biosynthesis of trna t⁶a in escherichia coli. nucleic acids res., 43, 1804-1817.
8. zhang, w., collinet, b., graille, m., daugeron, m.c., lazar, n., libri, d., durand, d. and van tilbeurgh, h. (2015) crystal structures of the gon7/pcc1 and bud32/cgi121 complexes provide a model for the complete yeast keops complex. nucleic acids res., 43, 3358-3372.
9. perrochia, l., crozat, e., hecker, a., zhang, w., bareille, j., collinet, b., van tilbeurgh, h., forterre, p. and basta, t. (2013) in vitro biosynthesis of a universal t⁶a trna modification in archaea and eukarya. nucleic acids res., 41, 1953-1964.
10. he, j., shi, j., xu, x., zhang, w., wang, y., chen, x., du, y., zhu, n., zhang, j., wang, q. et al. (2012) stat3 mutations correlated with hyper-ige syndrome lead to blockage of il-6/stat3 signalling pathway. journal of biosciences, 37, 243-257.
11. jiang, p., xu, x., chen, y., zhang, w., serradji, n., yang, j., dong, c. and wang, q. (2010) pms-1077, a paf antagonist, induced differentiation of hl-60 cells with its novel activity. cell biology international, 34, 1227-1230.
12. zhang, w., lv, m., hai, j., wang, q. and wang, q. (2010) dicranostigma leptopodum (maxim) fedde induced apoptosis in smmc-7721 human hepatoma cells and inhibited tumor growth in mice. natural science, 2, 457-463.
13. zhang, w., yang, y., lin, c. and wang, q. (2010) antioxidant attenuation of ros-involved cytotoxicity induced by paraquat on hl-60 cells. health, 2, 235-261.

组织承办第四届全国核糖核酸（rna）青年学术会议（2022.07.24-26，兰州），敬请关注！