相较于偶发的基因组突变和水平基因转移等事件，细菌个体在表型层面的变化（Variation）乃至分化（Diversification）几乎每时每刻都在发生。细胞间的表型差异可帮助少量病原菌个体在面对宿主免疫和抗生素胁迫时维持生存、生长、乃至扩张，这些个体的生存繁衍则为病原菌的临床进化提供了关键的物质基础——基因组的复制。深入研究病原菌在复杂条件下的表型异质性（Phenotypic heterogeneity）及其底层分子机制可以帮助我们更好地理解病原菌在宿主感染及药物治疗过程中的行为模式，预测其可能的临床进化方向，寻找被忽视的药物靶点。 

　 本研究组将结合高通量显微成像、高通量群体及单细菌测序等方法，系统性地刻画重要病原菌在不同环境下的单细菌表型和基因表达谱，追踪病原菌在宿主间传播，建立感染，耐受抗生素杀灭，抵御宿主免疫抑制等重要步骤中的表型分化过程，鉴定关键的细菌亚群及其分子基础，为临床预防、检测和治疗方案的优化提供新的技术和理论支撑。

 代表性论文（#共同一作，*共同通讯）

1. Harim I. Won,Junhao Zhu#*, Olga Kandror, Tatos Akopian, Ian D. Wolf, Michael C. Chao, Maya Waldor, Eric J. Rubin. Chemically-induced targeted protein degradation in mycobacteria uncovers antibacterial effects and potentiates antibiotic efficacy.BioRxiv, 2023.

2.Junhao Zhu, Yue J. Liu, Sarah M. Fortune. Spatiotemporal perspectives on tuberculosis chemotherapy.Current Opinion in Microbiology2023, 72:102266.

3. Qingyun Liu,Junhao Zhu#, Charles L Dulberger, Sydney Stanley, Sean Wilson, Eun Seon Chung, Xin Wang, Peter Culviner, Yue J. Liu, Nathan D. Hicks, Gregory H. Babunovic, Samantha R. Giffen, Bree B. Aldridge, Ethan C. Garner, Eric J. Rubin, Michael C. Chao, Sarah M. Fortune. Tuberculosis treatment failure associated with evolution of antibiotic resilience.Science2022, 378(6624):1111-1118.

4.Junhao Zhu, Ian D. Wolf, Charles L. Dulberger, Harim I. Won, Jemila C. Kester, Julius A. Judd, Samantha E. Wirth, Ryan R. Clark, Yawei Li, Yuan Luo, Todd A Gray, Joseph T Wade, Keith M Derbyshire, *Sarah M Fortune, Eric J Rubin. Spatiotemporal localization of proteins in mycobacteria.Cell Reports2021, 37(13):110154.

5. Biwei Wang,Junhao Zhu#, Babak Javid. Clinically relevant mutations in mycobacterial LepA cause rifampicin-specific phenotypic resistance.Scientific Reports2020, 21;10(1):8402.

6.Junhao Zhu#, Biwei Wang, Miaomiao Pan, Yuna Zeng, Hesper Rego, Babak Javid. Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes inrpoBtranscription.Nature Communications2018, 9(1):4218.

7. Hongwei Su,Junhao Zhu#, Hao Li, Rongjun Cai, Christopher Ealand, Xun Wang, Yuxiang Chen, Masood Ur Rehman Kayani, Ting F. Zhu, Danesh Moradigaravand, Hairong Huang, Bavesh D Kana, Babak Javid. The essential mycobacterial amidotransferase GatCAB is a modulator of specific translational fidelity.Nature Microbiology2016, 1(11):16147.

8. Chidiebere Akusobi, Bouchra S Benghomari,Junhao Zhu, Ian D Wolf, Shreya Singhvi, Charles L Dulberger, Thomas R Ioerger, *Eric J Rubin. Transposon mutagenesis inMycobacterium abscessusidentifies an essential penicillin-binding protein involved in septal peptidoglycan synthesis and antibiotic sensitivity.Elife2022, 11:e71947.

9. Yiwei Zhang,Junhao Zhu, Zhengqi Wang, You Wu, Xianbin Meng, Xuhui Zheng, Babak Javid. HspX promotes the polar localization of mycobacterial protein aggregates.Scientific Reports2019, 9(1):14571.

 代表性图片

Zhu et. al., Cell Rep., 2021

Zhu et. al., Nat. Comm., 2018 

 Liu and Zhu et. al., Science, 2022 

 工作人员

　　姜威 博士、助理研究员

 客座人员

　　周彤彤 在读硕士