单分子水平的酶催化与基因表达研究

Enzyme Catalysis and Gene Expression Studies at Single Molecule Level

近半个多世纪以来生命科学取得了非凡的进展,从DNA双螺旋结构的提出,到第一个酶晶体结构的被解析,都得益于像X射线衍射、核磁共振、质谱这样的物理化学工具的发展.如今,在深入细致地定量研究生物活体系统中我们正面临新的挑战,例如:了解酶及其他大分子复合物在体内是如何实时工作的,它们在分子数很少时是怎样工作的,在活细胞中大分子复合物是如何协调工作的,以及不同的基因在活细胞中分子数很少的情况下是如何实现表达和不表达的等等.近十多年来,单分子成像,超高分辨率显微镜和单分子操纵技术在世界范围内被广泛地运用于生物医学研究,对生物化学和分子生物学的发展产生着深远的影响,因为运用这些单分子、超高分辨技术,使很多如上述的令人感兴趣的生物学问题实现了单分子层面上的研究和理解.本文拟就近年来相关的物理化学方法特别是单分子方法和技术在生物医学中的应用做一个简要介绍.

Over the last half century, the overwhelming advances in biological sciences have been greatly aided by the physical and technological innovations, such as X-ray diffraction methods, nuclear magnetic resonance （NMR） and mass spectroscopy, etc.In recent years, single-molecule experiments have changed the way many biological problems are addressed.Knowledge from these experiments continues to emerge.We are now able to follow biochemical reactions of a single enzyme molecule in real time, and monitor gene expression in a living cell on a single molecule basis.These new methodologies will likely revolutionize our understanding of biological systems for many years to come.In this review, we highlight the achievements in the past decade in the fields of single molecule enzymology, live cell studies of gene expression and DNA protein interactions, emphasizing on the work of Sunney Xie′s laboratory.