Functional genomics reveal that the serine synthesis pathway is essential in breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.     

生物学概念的变化

面对目前迅猛发展的生物科学研究手段和研究方法，阐述了传统生物学概念的变化，现代生物学存在的不足和适应这种变化要做的工作．     

Evaluating probability forecasts in terms of refinement and strictly proper scoring rules

This note gives an easily verified necessary and sufficient condition for one probability forecaster to empirically outperform another one in terms of all strictly proper scoring rules. Copyright © 2006 John Wiley & Sons, Ltd.     

走向生物技术世纪

20世纪是物理学的世纪。在这个世纪，我们分裂了原子，使硅变成了微处理动力。现在是吗钟欢迎对世纪──生物技术世纪的时候了。正如1897年发现电子对对世纪具有开创性意义一样，21世纪的种子是在1953年开始萌发的。当时，詹姆斯·沃生（JamesWatson）脱口而出告诉他的合作者弗兰西斯·克里克（FrancisCrick），4种核音酸顺序成对配合构成的DNA分子，携带着具有自我复制功能的遗传密码。现在，我们离人类历史上最重大的突破之一：彻底阐释人类基因组，阐释我们的DNA中由30亿个化学组编码排序而成的10万多条基因，只有短短的几年时间了。…     

经典数理物理学——动力学系统和场理论第三版

本书是关于经典数理物理学方面的专著，出版以来，一直受到物理及相关科学的重视，现已出版第三版。