Dr. Qian Peter SU is now a Postdoctoral Research Associate under the guidance of ARC Future Fellow Prof. Dayong JIN in Institute for Biomedical Materials & Devices (IBMD), University of Technology Sydney. He received his Ph.D. major in Single-Molecule Biophysics under the guidance of Prof. Xiaoliang Sunney XIE and Prof. Yujie SUN in 2017 from Biodynamic Optical Imaging Center (BIOPIC), Peking University with the honour of “Outstanding Graduate Student of the Beijing City”. In 2012, he took an oversea exchange scholarship and received mentorship on instrumentation of super resolution microscopy in Profs Xiaoliang Sunney Xie and Xiaowei Zhuang’s labs at Harvard University. He received his B.E. major in Bio-engineering under the guidance of Dr. Linhong DENG in 2011 from College of Bioengineering, Chongqing University.
Scientific training in Bio-Engineering, Bio-Physics, Molecular Biology (biochemistry, molecular genetics, protein purification, immuno-staining), and Cell Biology (cell culture, cell transfection, cell cycle controlling);
Skilled in Single-Molecule imaging, tracking and manipulation (TIRFM/RLS/OMTC/Magnetic Tweezers/Optical Tweezers);
Familiar with intracellular bio-membrane deformation/reformation/dynamics;
Good at in vitro re-constitution system, especially for motor proteins and bio-membranes;
Familiar with cell nucleus, chromatin structure and DNA replication;
Well skilled in Super-Resolution Microscopy (STORM/dSTORM/PALM/fPALM/RLSM/RESOLFT/ Two-Photon/Confocal); Skilled in theory, software, optical and hardware system construction, cell culturing, specific target labeling, sample preparation, imaging and data collecting, algorithm writing, data analysis, data mining, imaging rendering and data presentation;
Skilled in MATLAB codes writing, mathematical modeling and data mining;
Able to design projects and execute experiments independently, also good at team-work, experienced with manuscript preparation and funding application
Can supervise: YES
Dr. Qian Peter SU's research interests are:
i) Developing advanced Single-Molecule imaging, tracking and manipulation techniques to study motor proteins/cytoskeleton driven intracellular bio-membrane deformation/reformation/dynamics and the underlying molecular mechanisms, especially using in vitro re-constitution systems (Su, Sci. Rep 2016; Chen, Curr. Prot. Cell Biol. 2018, Du, Dev. Cell 2016, Wang, Cell Res. 2015; Guan, Nat. Comm. 2017; Shen, PNAS 2016);
ii) Developing and applying cutting-edge Super-Resolution imaging systems and algorithms (especially STORM and PALM) to resolve the precise structure of subcellular organelles, to map the spatio-temporal distribution of important proteins, to pinpoint the hierarchical chromatin structures as well as structure-mediated replication and transcription mechanisms in mammalian cells and bacterial nucleus (Liu, Nat. Comm. 2014; Ren, Chem. Sci. 2018, Li, Mol. Oral Micro. 2015; Hao, Biophy. J. 2017; Su, Chi. Sci. Bull. 2014).
Ren, W., Wen, S., Tawfik, S.A., Su, Q.P., Lin, G., Ju, L.A., Ford, M.J., Ghodke, H., van Oijen, A.M. & Jin, D. 2018, 'Anisotropic functionalization of upconversion nanoparticles.', Chemical science, vol. 9, no. 18, pp. 4352-4358.View/Download from: UTS OPUS or Publisher's site
Despite significant advances toward accurate tuning of the size and shape of colloidal nanoparticles, the precise control of the surface chemistry thereof remains a grand challenge. It is desirable to conjugate functional bio-molecules onto the selected facets of nanoparticles owing to the versatile capabilities rendered by the molecules. We report here facet-selective conjugation of DNA molecules onto upconversion nanoparticles via ligand competition reaction. Different binding strengths of phosphodiester bonds and phosphate groups on DNA and the surfactant molecules allow one to create heterogeneous bio-chemistry surface for upconversion nanoparticles. The tailored surface properties lead to the formation of distinct self-assembly structures. Our findings provide insight into the interactions between biomolecules and nanoparticles, unveiling the potential of using nanoparticles as fundamental building blocks for creating self-assembled nano-architectures.
Guan, R., Zhang, L., Su, Q.P., Mickolajczyk, K.J., Chen, G.-.Y., Hancock, W.O., Sun, Y., Zhao, Y. & Chen, Z. 2017, 'Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin.', Nature communications, vol. 8, p. 14951.View/Download from: UTS OPUS or Publisher's site
Kinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding 6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension. The backward-docked structure of NIS is essential for motility of the motor. Our findings reveal a key missing conformation of kinesins, which provides the structural basis of the stable 2HB state and offers a tension-based rationale for an optimal NL length to ensure processivity of the motor.
Hao, H., Su, Q., Zhao, S. & Sun, Y. 2017, 'Golgi Microtubules are Hyper-Acetylated and Participate in Fast Cargo Trafficking', Biophysical Journal, vol. 112, no. 3, pp. 238a-238a.View/Download from: Publisher's site
Du, W., Su, Q.P., Chen, Y., Zhu, Y., Jiang, D., Rong, Y., Zhang, S., Zhang, Y., Ren, H., Zhang, C., Wang, X., Gao, N., Wang, Y., Sun, L., Sun, Y. & Yu, L. 2016, 'Kinesin 1 Drives Autolysosome Tubulation.', Developmental cell, vol. 37, no. 4, pp. 326-336.View/Download from: UTS OPUS or Publisher's site
Autophagic lysosome reformation (ALR) plays an important role in maintaining lysosome homeostasis. During ALR, lysosomes are reformed by recycling lysosomal components from autolysosomes. The most noticeable step of ALR is autolysosome tubulation, but it is currently unknown how the process is regulated. Here, using an approach combining in vivo studies and in vitro reconstitution, we found that the kinesin motor protein KIF5B is required for autolysosome tubulation and that KIF5B drives autolysosome tubulation by pulling on the autolysosomal membrane. Furthermore, we show that KIF5B directly interacts with PtdIns(4,5)P2. Kinesin motors are recruited and clustered on autolysosomes via interaction with PtdIns(4,5)P2 in a clathrin-dependent manner. Finally, we demonstrate that clathrin promotes formation of PtdIns(4,5)P2-enriched microdomains, which are required for clustering of KIF5B. Our study reveals a mechanism by which autolysosome tubulation was generated.
Shen, M., Zhang, N., Zheng, S., Zhang, W.-.B., Zhang, H.-.M., Lu, Z., Su, Q.P., Sun, Y., Ye, K. & Li, X.-.D. 2016, 'Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor.', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 40, pp. E5812-E5820.View/Download from: UTS OPUS or Publisher's site
The motor function of vertebrate myosin-5a is inhibited by its tail in a Ca2+-dependent manner. We previously demonstrated that the calmodulin (CaM) bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a is responsible for the Ca2+-dependent regulation of myosin-5a. We have solved the crystal structure of a truncated myosin-5a containing the motor domain and IQ1 (MD-IQ1) complexed with Ca2+-bound CaM (Ca2+-CaM) at 2.5-Å resolution. Compared with the structure of the MD-IQ1 complexed with essential light chain (an equivalent of apo-CaM), MD-IQ1/Ca2+-CaM displays large conformational differences in IQ1/CaM and little difference in the motor domain. In the MD-IQ1/Ca2+-CaM structure, the N-lobe and the C-lobe of Ca2+-CaM adopt an open conformation and grip the C-terminal and the N-terminal portions of the IQ1, respectively. Remarkably, the interlobe linker of CaM in IQ1/Ca2+-CaM is in a position opposite that in IQ1/apo-CaM, suggesting that CaM flip-flops relative to the IQ1 during the Ca2+ transition. We demonstrated that CaM continuously associates with the IQ1 during the Ca2+ transition and that the binding of CaM to IQ1 increases Ca2+ affinity and substantially changes the kinetics of the Ca2+ transition, suggesting that the IQ1/CaM complex functions as an intact Ca2+ sensor responding to distinct calcium signals.
Su, Q.P., Du, W., Ji, Q., Xue, B., Jiang, D., Zhu, Y., Lou, J., Yu, L. & Sun, Y. 2016, 'Vesicle Size Regulates Nanotube Formation in the Cell', Scientific Reports, vol. 6, pp. 24002-24002.View/Download from: UTS OPUS or Publisher's site
Intracellular membrane nanotube formation and its dynamics play important roles for cargo transportation and organelle biogenesis. Regarding the regulation mechanisms, while much attention has been paid on the lipid composition and its associated protein molecules, effects of the vesicle size has not been studied in the cell. Giant unilamellar vesicles (GUVs) are often used for in vitro membrane deformation studies, but they are much larger than most intracellular vesicles and the in vitro studies also lack physiological relevance. Here, we use lysosomes and autolysosomes, whose sizes range between 100 nm and 1 m, as model systems to study the size effects on nanotube formation both in vivo and in vitro. Single molecule observations indicate that driven by kinesin motors, small vesicles (100-200 nm) are mainly transported along the tracks while a remarkable portion of large vesicles (500-1000 nm) form nanotubes. This size effect is further confirmed by in vitro reconstitution assays on liposomes and purified lysosomes and autolysosomes. We also apply Atomic Force Microscopy (AFM) to measure the initiation force for nanotube formation. These results suggest that the size-dependence may be one of the mechanisms for cells to regulate cellular processes involving membrane-deformation, such as the timing of tubulation-mediated vesicle recycling.
Li, R., Zhang, W., Su, Q.P., Xue, B. & Sun, Y. 2015, 'Structural and Functional Study of Midbody during Cytokinesis', BIOPHYSICAL JOURNAL, vol. 108, no. 2, pp. 631A-631A.View/Download from: UTS OPUS or Publisher's site
Li, Y., Liu, Z., Zhang, Y., Su, Q.P., Xue, B., Shao, S., Zhu, Y., Xu, X., Wei, S. & Sun, Y. 2015, 'Live-cell and super-resolution imaging reveal that the distribution of wall-associated protein A is correlated with the cell chain integrity of Streptococcus mutans.', Mol Oral Microbiol, vol. 30, no. 5, pp. 376-383.View/Download from: UTS OPUS or Publisher's site
Streptococcus mutans is a primary pathogen responsible for dental caries. It has an outstanding ability to form biofilm, which is vital for virulence. Previous studies have shown that knockout of Wall-associated protein A (WapA) affects cell chain and biofilm formation of S. mutans. As a surface protein, the distribution of WapA remains unknown, but it is important to understand the mechanism underlying the function of WapA. This study applied the fluorescence protein mCherry as a reporter gene to characterize the dynamic distribution of WapA in S. mutans via time-lapse and super-resolution fluorescence imaging. The results revealed interesting subcellular distribution patterns of WapA in single, dividing and long chains of S. mutans cells. It appears at the middle of the cell and moves to the poles as the cell grows and divides. In a cell chain, after each round of cell division, such dynamic relocation results in WapA distribution at the previous cell division sites, resulting in a pattern where WapA is located at the boundary of two adjacent cell pairs. This WapA distribution pattern corresponds to the breaking segmentation of wapA deletion cell chains. The dynamic relocation of WapA through the cell cycle increases our understanding of the mechanism of WapA in maintaining cell chain integrity and biofilm formation.
Mi, N., Chen, Y., Wang, S., Chen, M., Zhao, M., Yang, G., Ma, M., Su, Q., Luo, S., Shi, J., Xu, J., Guo, Q., Gao, N., Sun, Y., Chen, Z. & Yu, L. 2015, 'CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane.', Nat Cell Biol, vol. 17, no. 9, pp. 1112-1123.View/Download from: UTS OPUS or Publisher's site
A fundamental question regarding autophagosome formation is how the shape of the double-membrane autophagosomal vesicle is generated. Here we show that in mammalian cells assembly of an actin scaffold inside the isolation membrane (the autophagosomal precursor) is essential for autophagosomal membrane shaping. Actin filaments are depolymerized shortly after starvation and actin is assembled into a network within the isolation membrane. When formation of actin puncta is disrupted by an actin polymerization inhibitor or by knocking down the actin-capping protein CapZ, isolation membranes and omegasomes collapse into mixed-membrane bundles. Formation of actin puncta is PtdIns(3)P dependent, and inhibition of PtdIns(3)P formation by treating cells with the PI(3)K inhibitor 3-MA, or by knocking down Beclin-1, abolishes the formation of actin puncta. Binding of CapZ to PtdIns(3)P, which is enriched in omegasomes, stimulates actin polymerization. Our findings illuminate the mechanism underlying autophagosomal membrane shaping and provide key insights into how autophagosomes are formed.
Wang, C., Du, W., Su, Q.P., Zhu, M., Feng, P., Li, Y., Zhou, Y., Mi, N., Zhu, Y., Jiang, D., Zhang, S., Zhang, Z., Sun, Y. & Yu, L. 2015, 'Dynamic tubulation of mitochondria drives mitochondrial network formation.', Cell Res, vol. 25, no. 10, pp. 1108-1120.View/Download from: UTS OPUS or Publisher's site
Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, whereas disruption of the mitochondrial network affects mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. Here, we report a new mechanism for formation of mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria. We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria. Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to the mitochondrial network. We further demonstrated that dynamic tubulation and fusion is sufficient for mitochondrial network formation, by reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only controls network formation in the peripheral zone of the cell, indicating that the mitochondrial network is divided into subzones, which may be constructed by different mechanisms. Our data not only uncover an essential mechanism for mitochondrial network formation, but also reveal that different parts of the mitochondrial network are formed by different mechanisms.
Wang, G., Li, Y., Wang, P., Liang, H., Cui, M., Zhu, M., Guo, L., Su, Q., Sun, Y., McNutt, M.A. & Yin, Y. 2015, 'PTEN regulates RPA1 and protects DNA replication forks.', Cell research, vol. 25, no. 11, pp. 1189-1204.View/Download from: UTS OPUS or Publisher's site
Tumor suppressor PTEN regulates cellular activities and controls genome stability through multiple mechanisms. In this study, we report that PTEN is necessary for the protection of DNA replication forks against replication stress. We show that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea. PTEN is physically associated with replication protein A 1 (RPA1) via the RPA1 C-terminal domain. STORM and iPOND reveal that PTEN is localized at replication sites and promotes RPA1 accumulation on replication forks. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. RPA1 deletion confers a phenotype like that observed in PTEN knockout cells with stalling of replication forks. Expression of PTEN and RPA1 shows strong correlation in colorectal cancer. Heterozygous disruption of RPA1 promotes tumorigenesis in mice. These results demonstrate that PTEN is essential for DNA replication fork protection. We propose that RPA1 is a target of PTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.
Liu, Z., Xing, D., Su, Q.P., Zhu, Y., Zhang, J., Kong, X., Xue, B., Wang, S., Sun, H., Tao, Y. & Sun, Y. 2014, 'Super-resolution imaging and tracking of protein–protein interactions in sub-diffraction cellular space', Nature Communications, vol. 5, pp. 1-8.View/Download from: UTS OPUS or Publisher's site
Imaging the location and dynamics of individual interacting protein pairs is essential but often difficult because of the fluorescent background from other paired and non-paired molecules, particularly in the sub-diffraction cellular space. Here we develop a new method combining bimolecular fluorescence complementation and photoactivated localization microscopy for super-resolution imaging and single-molecule tracking of specific protein–protein interactions. The method is used to study the interaction of two abundant proteins, MreB and EF-Tu, in Escherichia coli cells. The super-resolution imaging shows interesting distribution and domain sizes of interacting MreB–EF-Tu pairs as a subpopulation of total EF-Tu. The single-molecule tracking of MreB, EF-Tu and MreB–EF-Tu pairs reveals intriguing localization-dependent heterogonous dynamics and provides valuable insights to understanding the roles of MreB–EF-Tu interactions.