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 and cytoskeleton driven intracellular bio-membrane deformation/reformation/dynamics and the underlying molecular mechanisms, especially using in vitro re-constitution systems (Biophy. Rev. 2018, Sci. Rep 2016, Curr. Prot. Cell Biol. 2018, Dev. Cell 2016, Cell Res. 2015; Nat. Comm. 2017; 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 spatial-temporal distribution of important proteins, to pinpoint the molecular mechanism during platelet decision-making process for cardiovascular diseases, to reveal the hierarchical chromatin structures as well as structure-mediated replication and transcription mechanisms in mammalian cells and bacterial nucleus (Biophy. Rev. 2018; Nat. Comm. 2014; Chem. Sci. 2018, Mol. Oral Micro. 2015; Biophy. J. 2017; Chi. Sci. Bull. 2014)
© Springer Science+Business Media, LLC, part of Springer Nature 2019. Autophagic lysosome reformation (ALR) is the terminal step of autophagy. ALR functions to recycle lysosomal membranes and maintain lysosome homeostasis. Maintaining a functional lysosome pool is critical for generating autolysosomes, in which cellular components are degraded and turned over during autophagy. This unit describes methods to visualize ALR in cells. In addition, this unit provides detailed protocols to establish in vitro systems which can be used to reconstitute ALR as well as to reconstitute mitochondrial tubulation/network formation, another process that is driven by motor proteins.
Su, QP, Zhao, ZW, Meng, L, Ding, M, Zhang, W, Li, Y, Liu, M, Li, R, Gao, Y-Q, Xie, XS & Sun, Y 2019, 'CTCF-mediated Chromatin Structures Dictate the Spatio-temporal Propagation of Replication Foci: Supplementary Materials'.View/Download from: Publisher's site
Mammalian DNA replication is initiated at numerous replication origins, which are clustered into thousands of replication domains (RDs) across the genome. However, it remains unclear whether the replication origins within each RD are activated stochastically. To understand how replication is regulated at the sub-RD level, we directly visualized the spatio-temporal organization, morphology, and in situ epigenetic signatures of individual replication foci (RFi) across S-phase using super-resolution stochastic optical reconstruction microscopy (STORM). Importantly, we revealed a hierarchical radial pattern of RFi propagation that reverses its directionality from early to late S-phase, and is diminished upon caffeine treatment or CTCF knockdown. Together with simulation and bioinformatic analyses, our findings point to a "CTCF-organized REplication Propagation" (CoREP) model. The CoREP model suggests a non-random selection mechanism for replication activation mediated by CTCF at the sub-RD level, as well as the critical involvement of local chromatin environment in regulating replication in space and time.
Chen, Y, Ju, LA, Zhou, F, Liao, J, Xue, L, Su, QP, Jin, D, Yuan, Y, Lu, H, Jackson, SP & Zhu, C 2019, 'An integrin IIb3 intermediate affinity state mediates biomechanical platelet aggregation.', Nature materials.View/Download from: Publisher's site
Integrins are membrane receptors that mediate cell adhesion and mechanosensing. The structure-function relationship of integrins remains incompletely understood, despite the extensive studies carried out because of its importance to basic cell biology and translational medicine. Using a fluorescence dual biomembrane force probe, microfluidics and cone-and-plate rheometry, we applied precisely controlled mechanical stimulations to platelets and identified an intermediate state of integrin IIb3 that is characterized by an ectodomain conformation, ligand affinity and bond lifetimes that are all intermediate between the well-known inactive and active states. This intermediate state is induced by ligand engagement of glycoprotein (GP) Ib via a mechanosignalling pathway and potentiates the outside-in mechanosignalling of IIb3 for further transition to the active state during integrin mechanical affinity maturation. Our work reveals distinct IIb3 state transitions in response to biomechanical and biochemical stimuli, and identifies a role for the IIb3 intermediate state in promoting biomechanical platelet aggregation.
Chen, Y, Su, QP, Sun, Y & Yu, L 2018, 'Visualizing Autophagic Lysosome Reformation in Cells Using In Vitro Reconstitution Systems.', Current protocols in cell biology, vol. 78, no. 1, pp. 11.24.1-11.24.15.View/Download from: UTS OPUS or Publisher's site
Autophagy is a lysosome-based degradation pathway. Autophagic lysosome reformation (ALR) is a lysosomal membrane recycling process that marks the terminal step of autophagy. During ALR, LAMP1-positive tubules, named reformation tubules, are extruded from autolysosomes, and nascent lysosomes are generated from these tubules. By combining proteomic analysis of purified autolysosomes and RNA interference screening of identified candidates, we systematically elucidated the ALR pathway at the molecular level. Based on the key components clathrin, PtdIns(4,5)P2 , and the motor protein KIF5B, among others, we reconstituted this process in vitro. This unit describes a detailed method for visualizing ALR in cells during the autophagy process. This unit also present a protocol for reconstituting the ALR tubular protrusion and elongation process in vitro and three methods for preparing materials for in vitro reconstitution: (1) autolysosome purification from cultured cells, (2) liposome preparation, and (3) KIF5B purification and quality testing. © 2018 by John Wiley & Sons, Inc.
© 2018, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature. The focus of the cell biology field is now shifting from characterizing cellular activities to organelle and molecular behaviors. This process accompanies the development of new biophysical visualization techniques that offer high spatial and temporal resolutions with ultra-sensitivity and low cell toxicity. They allow the biology research community to observe dynamic behaviors from scales of single molecules, organelles, cells to organoids, and even live animal tissues. In this review, we summarize these biophysical techniques into two major classes: the mechanical nanotools like dynamic force spectroscopy (DFS) and the optical nanotools like single-molecule and super-resolution microscopy. We also discuss their applications in elucidating molecular dynamics and functionally mapping of interactions between inter-cellular networks and intra-cellular components, which is key to understanding cellular processes such as adhesion, trafficking, inheritance, and division.
Chen, C, Wang, F, Wen, S, Su, QP, Wu, MCL, Liu, Y, Wang, B, Li, D, Shan, X, Kianinia, M, Aharonovich, I, Toth, M, Jackson, SP, Xi, P & Jin, D 2018, 'Multi-photon near-infrared emission saturation nanoscopy using upconversion nanoparticles.', Nature communications, vol. 9, no. 1.View/Download from: UTS OPUS or Publisher's site
Multiphoton fluorescence microscopy (MPM), using near infrared excitation light, provides increased penetration depth, decreased detection background, and reduced phototoxicity. Using stimulated emission depletion (STED) approach, MPM can bypass the diffraction limitation, but it requires both spatial alignment and temporal synchronization of high power (femtosecond) lasers, which is limited by the inefficiency of the probes. Here, we report that upconversion nanoparticles (UCNPs) can unlock a new mode of near-infrared emission saturation (NIRES) nanoscopy for deep tissue super-resolution imaging with excitation intensity several orders of magnitude lower than that required by conventional MPM dyes. Using a doughnut beam excitation from a 980nm diode laser and detecting at 800nm, we achieve a resolution of sub 50nm, 1/20th of the excitation wavelength, in imaging of single UCNP through 93m thick liver tissue. This method offers a simple solution for deep tissue super resolution imaging and single molecule tracking.
Ren, W, Wen, S, Tawfik, SA, Su, QP, Lin, G, Ju, LA, Ford, MJ, Ghodke, H, van Oijen, AM & 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, QP, Mickolajczyk, KJ, Chen, G-Y, Hancock, WO, 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.View/Download from: UTS OPUS or Publisher's site
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
Shen, M, Zhang, N, Zheng, S, Zhang, W-B, Zhang, H-M, Lu, Z, Su, QP, 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
Du, W, Su, QP, 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
Su, QP, 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.
Wang, C, Du, W, Su, QP, 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.
Li, Y, Liu, Z, Zhang, Y, Su, QP, 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.
Li, R, Zhang, W, Su, QP, 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
Wang, G, Li, Y, Wang, P, Liang, H, Cui, M, Zhu, M, Guo, L, Su, Q, Sun, Y, McNutt, MA & 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
Liu, Z, Xing, D, Su, QP, 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.