Bio

Honors & Awards


  • Burroughs Wellcome Predoctoral Fellowship, Burroughs Wellcome Fund (2004-2009)
  • Joseph Henry Merit Prize, Princeton University (2004-2005)
  • Chun-Tsung Scholars, Chun-Tsung Endowment (2002-2004)

Professional Education


  • Doctor of Philosophy, Princeton University (2010)
  • Bachelor of Science, Peking University, Physics (2004)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


Studying design principles of Caulobacter crescentus cell-cycle circuit by introducing genetic modifications into the circuit and applying live-cell time-lapse microscopy to track dynamics of fluorescently-labeled master cell-cycle regulators

Publications

Journal Articles


  • Measurement of the Copy Number of the Master Quorum-Sensing Regulator of a Bacterial Cell BIOPHYSICAL JOURNAL Teng, S., Wang, Y., Tu, K. C., Long, T., Mehta, P., Wingreen, N. S., Bassler, B. L., Ong, N. P. 2010; 98 (9): 2024-2031

    Abstract

    Quorum-sensing is the mechanism by which bacteria communicate and synchronize group behaviors. Quantitative information on parameters such as the copy number of particular quorum-sensing proteins should contribute strongly to understanding how the quorum-sensing network functions. Here, we show that the copy number of the master regulator protein LuxR in Vibrio harveyi can be determined in vivo by exploiting small-number fluctuations of the protein distribution when cells undergo division. When a cell divides, both its volume and LuxR protein copy number, N, are partitioned with slight asymmetries. We measured the distribution functions describing the partitioning of the protein fluorescence and the cell volume. The fluorescence distribution is found to narrow systematically as the LuxR population increases, whereas the volume partitioning is unchanged. Analyzing these changes statistically, we determined that N = 80-135 dimers at low cell density and 575 dimers at high cell density. In addition, we measured the static distribution of LuxR over a large (3000) clonal population. Combining the static and time-lapse experiments, we determine the magnitude of the Fano factor of the distribution. This technique has broad applicability as a general in vivo technique for measuring protein copy number and burst size.

    View details for DOI 10.1016/j.bpj.2010.01.031

    View details for Web of Science ID 000277377300037

    View details for PubMedID 20441767

  • Probing bacterial transmembrane histidine kinase receptor-ligand interactions with natural and synthetic molecules PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ng, W., Wei, Y., Perez, L. J., Cong, J., Long, T., Koch, M., Semmelhack, M. F., Wingreen, N. S., Bassler, B. L. 2010; 107 (12): 5575-5580

    Abstract

    Bacterial histidine kinases transduce extracellular signals into the cytoplasm. Most stimuli are chemically undefined; therefore, despite intensive study, signal recognition mechanisms remain mysterious. We exploit the fact that quorum-sensing signals are known molecules to identify mutants in the Vibrio cholerae quorum-sensing receptor CqsS that display altered responses to natural and synthetic ligands. Using this chemical-genetics approach, we assign particular amino acids of the CqsS sensor to particular roles in recognition of the native ligand, CAI-1 (S-3 hydroxytridecan-4-one) as well as ligand analogues. Amino acids W104 and S107 dictate receptor preference for the carbon-3 moiety. Residues F162 and C170 specify ligand head size and tail length, respectively. By combining mutations, we can build CqsS receptors responsive to ligand analogues altered at both the head and tail. We suggest that rationally designed ligands can be employed to study, and ultimately to control, histidine kinase activity.

    View details for DOI 10.1073/pnas.1001392107

    View details for Web of Science ID 000275898300056

    View details for PubMedID 20212168

  • Negative Feedback Loops Involving Small Regulatory RNAs Precisely Control the Vibrio harveyi Quorum-Sensing Response MOLECULAR CELL Tu, K. C., Long, T., Svenningsen, S. L., Wingreen, N. S., Bassler, B. L. 2010; 37 (4): 567-579

    Abstract

    Quorum-sensing (QS) bacteria assess population density through secretion and detection of molecules called autoinducers (AIs). We identify and characterize two Vibrio harveyi negative feedback loops that facilitate precise transitions between low-cell-density (LCD) and high-cell-density (HCD) states. The QS central regulator LuxO autorepresses its own transcription, and the Qrr small regulatory RNAs (sRNAs) posttranscriptionally repress luxO. Disrupting feedback increases the concentration of AIs required for cells to transit from LCD to HCD QS modes. Thus, the two cooperative negative feedback loops determine the point at which V. harveyi has reached a quorum and control the range of AIs over which the transition occurs. Negative feedback regulation also constrains the range of QS output by preventing sRNA levels from becoming too high and preventing luxO mRNA levels from reaching zero. We suggest that sRNA-mediated feedback regulation is a network design feature that permits fine-tuning of gene regulation and maintenance of homeostasis.

    View details for DOI 10.1016/j.molcel.2010.01.022

    View details for Web of Science ID 000275349000014

    View details for PubMedID 20188674

  • Information processing and signal integration in bacterial quorum sensing MOLECULAR SYSTEMS BIOLOGY Mehta, P., Goyal, S., Long, T., Bassler, B. L., Wingreen, N. S. 2009; 5

    Abstract

    Bacteria communicate using secreted chemical signaling molecules called autoinducers in a process known as quorum sensing. The quorum-sensing network of the marine bacterium Vibrio harveyi uses three autoinducers, each known to encode distinct ecological information. Yet how cells integrate and interpret the information contained within these three autoinducer signals remains a mystery. Here, we develop a new framework for analyzing signal integration on the basis of information theory and use it to analyze quorum sensing in V. harveyi. We quantify how much the cells can learn about individual autoinducers and explain the experimentally observed input-output relation of the V. harveyi quorum-sensing circuit. Our results suggest that the need to limit interference between input signals places strong constraints on the architecture of bacterial signal-integration networks, and that bacteria probably have evolved active strategies for minimizing this interference. Here, we analyze two such strategies: manipulation of autoinducer production and feedback on receptor number ratios.

    View details for DOI 10.1038/msb.2009.79

    View details for Web of Science ID 000272308900004

    View details for PubMedID 19920810

  • Quantifying the Integration of Quorum-Sensing Signals with Single-Cell Resolution PLOS BIOLOGY Long, T., Tu, K. C., Wang, Y., Mehta, P., Ong, N. P., Bassler, B. L., Wingreen, N. S. 2009; 7 (3): 640-649

    Abstract

    Cell-to-cell communication in bacteria is a process known as quorum sensing that relies on the production, detection, and response to the extracellular accumulation of signaling molecules called autoinducers. Often, bacteria use multiple autoinducers to obtain information about the vicinal cell density. However, how cells integrate and interpret the information contained within multiple autoinducers remains a mystery. Using single-cell fluorescence microscopy, we quantified the signaling responses to and analyzed the integration of multiple autoinducers by the model quorum-sensing bacterium Vibrio harveyi. Our results revealed that signals from two distinct autoinducers, AI-1 and AI-2, are combined strictly additively in a shared phosphorelay pathway, with each autoinducer contributing nearly equally to the total response. We found a coherent response across the population with little cell-to-cell variation, indicating that the entire population of cells can reliably distinguish several distinct conditions of external autoinducer concentration. We speculate that the use of multiple autoinducers allows a growing population of cells to synchronize gene expression during a series of distinct developmental stages.

    View details for DOI 10.1371/journal.pbio.1000068

    View details for Web of Science ID 000265412600020

    View details for PubMedID 19320539

  • The yeast cell-cycle network is robustly designed PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Li, F. T., Long, T., Lu, Y., Ouyang, Q., Tang, C. 2004; 101 (14): 4781-4786

    Abstract

    The interactions between proteins, DNA, and RNA in living cells constitute molecular networks that govern various cellular functions. To investigate the global dynamical properties and stabilities of such networks, we studied the cell-cycle regulatory network of the budding yeast. With the use of a simple dynamical model, it was demonstrated that the cell-cycle network is extremely stable and robust for its function. The biological stationary state, the G1 state, is a global attractor of the dynamics. The biological pathway, the cell-cycle sequence of protein states, is a globally attracting trajectory of the dynamics. These properties are largely preserved with respect to small perturbations to the network. These results suggest that cellular regulatory networks are robustly designed for their functions.

    View details for DOI 10.1073/pnas.0305937101

    View details for Web of Science ID 000220761200013

    View details for PubMedID 15037758

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