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Posted: Monday, December 18, 2017 12:19 AM

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The Zhang lab at the Department of Cell Biology, Yale University, uses single-molecule approaches, especially high-resolution optical tweezers, to study folding dynamics of proteins involved in fundamental biological processes and human diseases. The lab is now seeking one or two postdocs for research in the following three areas:

Regulated SNARE folding and assembly. The membrane fusion machinery contains SNARE proteins, Sec1/Munc18 (SM) proteins, synaptotagmin, complexin, NSF, SNAP, and Munc13. Among these proteins, SNAREs are key players. They couple their dynamical assembly and disassembly to membrane fusion in a precisely controlled manner. Specifically, SNARE assembly generates force to draw two membranes into proximity and use their folding energy to lower the energy barrier of membrane fusion. SM proteins, synaptotagmin, and complexin regulate SNARE assembly and enable membrane fusion to occur at right time and location. After membrane fusion, NSF and SNAP disassemble the fully assembled SNARE complexes in an ATP-dependent manner, recycling SNAREs for next round of fusion. We plan to understand how the above mentioned proteins work together to control exocytosis.
Membrane protein folding, stability, and protein-membrane interactions. Optical tweezers have been widely applied to study folding dynamics of soluble proteins, but not membrane proteins so far. We have been developing novel approaches to measuring the folding energy and kinetics of membrane proteins using high-resolution optical tweezers. We are also interested in proteins that help membrane proteins get in and out membranes.
Instrumental development. We plan to upgrade our optical tweezers and single-molecule fluorescence spectroscopy. Skills in LabVIEW, optics, computer control, and data acquisition are required.
Prior research experience in single-molecule biophysics is favored, but not required. However, postdoc candidates should have strong quantitative skills and solid training in biophysics, molecular biology, or physics. If you are interested in these positions, please contact Dr. Yongli Zhang at yongli.zhang@yale.edu.

Representative publications:

Y. Gao, S. Zorman, G. Gundersen, Z. Q. Xi, G. Sirinakis, J. E. Rothman, Y. L. Zhang, Single reconstituted neuronal SNARE complexes zipper in three distinct stages. Science 337: 1340-1343 (2012).
X. M. Zhang, A. A. Rebane, F. Li, F. Pincet, J. E. Rothman, Y. L. Zhang, Stability, folding dynamics, and long-range conformational transition of the synaptic t-SNARE complex. Proc. Natl. Acad. Sci. U.S.A. 113, E8031-E8040 (2016).
J. Jiao, A. A. Rebane, L. Ma, Y. Gao, Y. L. Zhang, Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition. Proc. Natl. Acad. Sci. U.S.A. 112, E2855-E2864 (2015).
L. Ma, A. A. Rebane, G. Yang, Z. Xi, Y. Kang, Y. Gao, Y. L. Zhang, Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis. eLIFE 4, e09580 (2015).
S. Zorman, A. A. Rebane, L. Ma, G. Yang, M. A. Molski, J. Coleman, F. Pincet, J. E. Rothman, Y. L. Zhang, Common intermediates and kinetics, but different energetics, in the assembly of SNARE proteins. eLIFE 3, e03348 (2014).
G. Sirinakis, Y. X. Ren, Y. Gao, Z. Q. Xi, Y. L. Zhang, Combined and versatile high-resolution optical tweezers and single-molecule fluorescence microscopy. Rev Sci Instrum. 83: 093708-(1-9) (2012).
L. Ma, Y. Cai, Y. Li, J. Jiao, Z. Wu, B. O'Shaughnessy, E. Karatekin, P. De Camilli, Y. L. Zhang, Single-molecule force spectroscopy of protein-membrane interactions. eLIFE, (2017): https://elifesciences.org/articles/30493

• Location: New Haven

• Post ID: 20899867 newhaven
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