《PNAS》封面故事：生物膜融合过程

　　

生物通报道：来自霍华德休斯医学院，伊利诺伊大学香槟分校生物物理学与计算机生物学中心，以及爱荷华州大学的研究人员发现了一种新方法，可以观测到生物膜融合的过程。这可以帮助科学家们更进一步了解生物膜产生交互作用的机制，对于基础研究或药物研发都是很有用的工具。 这一研究成果公布在《美国国家科学院院刊》（PNAS）杂志上。

原文摘要：
Published online before print December 13, 2006, 10.1073/pnas.0606032103 
PNAS | December 26, 2006 | vol. 103 | no. 52 | 19731-19736 
Multiple intermediates in SNARE-induced membrane fusion 
[Abstract]

生物膜是细胞生存和维持细胞基本功能的基础。无容置疑地，了解这种基本的生命现象机制具有很大的生物利益，并且有助于广泛的研究和实验。之前的研究提出了各种生物膜融合的中间体，但是这些方法并未获得实际的影响证据。

在这篇文章中，这项重要的任务是由称为SNAREs 的膜蛋白质所达成的。研究人员利用萤光共振能量转移（FRET）法，研发出这种观察生物膜融合的方法。在FRET 法中，使用一对绿色和红色染料，只有绿色染料可以被雷射直接激发。如果有些能量从绿色染料转移至红色染料，那么红色染料就会发光，两种染料的距离越近，红色染料发光的效率越高。

研究人员利用萤光显微镜观察SNARE-SNARE间的交互作用，实时地观察到膜融合的影像。这种新方法可以帮助科学家们更进一步了解生物膜产生交互作用的机制，对于基础研究或药物研发都是很有用的工具。
（生物通：万纹）

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Taekjip Ha 

Associate Professor of Physics, Center for Biophysics and Computational Biology 
Affiliate, Department of Chemistry

Professor Ha received his B.S. degree in physics from Seoul National University, Korea 1990 and his Ph.D. from the University of California at Berkeley in 1996. He was a postdoctoral fellow at the Lawrence Berkeley National Laboratory and at Stanford and was briefly a visiting scientist at the Technical University of Denmark, Lyngby, Denmark. He joined the physics faculty at Illinois in 2000. 

Honors and Awards 
• Howard Hughes Medical Institute Investigator, 2005 
• Alfred P. Sloan Fellowship, 2003
• Beckman Fellow, UIUC Center for Advanced Studies, 2003
• Xerox Faculty Research Award, UIUC, 2003
• Cottrell Scholar Award, 2003
• NSF CAREER Award, 2002 
• Fluorescence Young Investigator Award, 2002 
• Searle Scholar Award, 2001 
• Research Innovation Award, 2001 
• Outstanding Young Researcher Award, AKPA, 2001 


Current Research
We are interested in using physical concepts and experimental techniques to study fundamental questions in molecular biology. The biological systems under study include helicases that unzip DNA, a DNA recombination intermediate called a Holliday junction and its associated enzymes, folding and catalysis of hairpin and VS ribozymes, DNA replication machinery, and chromatin remodeling complexes. 

Our main experimental tool is single-molecule fluorescence spectroscopy and microscopy, supported by nano-mechanical tools such as magnetic and optical tweezers. We use modern molecular biology techniques to engineer the molecules with fluorescence tags and tether them to a bio-friendly surface. Then, we shine laser light on each molecule to watch it do its thing. A clever design of such experiments can yield new insights to fundamental biological problems. We also use computational tools extensively, not only to acquire and analyze data, but also to model the problems mathematically, to exploit the genomic databases, and to simulate molecular motions and reactions. 

Representative Publications

"Repetitive shuttling of a motor protein on DNA", S. Myong, I. Rasnik, C. Joo, T.M. Lohman and T. Ha, Nature, (in press).

"Observing spontaneous branch migration of Holliday junctions one step at a time", S.A. McKinney, A. Freeman, D.M.J. Lilley and T. Ha, Proc.Nat.Acad.Sci. USA102, 5715-5720 (2005).

"Near-Complete Suppression Of Quantum Blinking In Ambient Conditions," S. Hohng and T. Ha, J. Am. Chem. Soc., 126, 1324 (2004).

"Observation Of Internal Cleavage and Ligation Reactions of a Ribozyme", M.K. Nahas, T.J. Wilson, S. Hohng, K.Jarvie, D.M.J. Lilley and T. Ha, Nature Structural & Molecular Biology, 11, 1107-1113 (2004).

"A Four-Way Junction Accelerates Hairpin Ribozyme Folding Via a Discrete Intermediate," E. Tan, T.J. Wilson, M.K. Nahas, R.M. Clegg, D.M.J. Lilley and T. Ha, Proc. Nat. Acad. Sci. USA, 100, 9308 (2003). 

"Myosin V Walks Hand-Over-Hand: Single Fluorophore Imaging With 1.5 nm Localization," A. Yildiz, J. Forkey, S.A. McKinney, T. Ha, Y.E. Goldman and P.R. Selvin, Science, 300, 2061 (2003). 

"Photodestruction Intermediates Probed By An Adjacent Reporter Molecule," T. Ha and J. Xu, Phys. Rev. Lett., 90, 223002 (2003).

"Structural Dynamics Of Individual Holliday Junctions," S.A. McKinney, A.C. Declais, D.M.J. Lilley and T. Ha, Nature Structural Biology, 10, 93 (2003).

"Initiation And Re-Initiation Of DNA Unwinding by the E. coli Rep Helicase," T. Ha, I. Rasnik, W. Cheng, H.P. Babcock, G. Gauss, T.M. Lohman and S. Chu, Nature, 419, 638 (2002).