Baylor 医学院分子和人类遗传学教授Dr. Hugo Bellen发明了P(acman) 方法, 该方法能将DNA插入果蝇基因组，克服了现在通用方法的关键障碍，能够在活体条件下研究大片段DNA，真正意义上实现研究果蝇全基因组结构和功能的方法。此外，该方法也可用于其它模式生物，如小鼠的研究中。研究成果刊登于11月30日Science杂志。
P/phiC31人工染色体（artificial chromosome），或称P(acman)，结合了三种最新技术：细菌人工染色体（bacterial artificial chromosome ，BAC，能够使大片段DNA维持在细菌中）、重组技术（recombineering）、能将大片段DNA插入果蝇基因组特定位点的phiC31-介导的转基因技术（phiC31-mediated transgenesis）。
Bellen评价这是一项意义深远的新技术。P(acman)越过了阻碍研究的绊脚石，能够将克隆得到的大片段DNA用于基因组转化，并且保证DNA片段插入基因组特异位点。目前研究基因机构和功能的技术都存在这样那样的问题，比如研究人员培育缺少特定基因的果蝇时，如果想将这种特定基因重新放入基因组中，那么插入位点经常是没有规律的。
有时会产生过多的蛋白，有时又产生的非常少，还有些情况下，这些重新插回的基因会影响其它基因的表达。
“在做这些的时候如同拿苹果和桔子相比，” Bellen。其它技术限于小的DNA片段。“Koen（发育生物学BCM计划一名研究生）利用这三种技术开发新的转基因系统。”
细菌人工染色体（BAC），使科学家能够将大片段DNA维持在细菌中，但是只有一个或少数几个拷贝。然而，细菌在必要时会产生许多DNA拷贝。
因此，Koen添加了重组（recombineering）技术。利用重组技术能够很方便地克隆出大片段DNA，并且可以在基因中的任意位点造成特异突变。
第三种技术能够帮助研究人员在果蝇基因组中寻找有潜力的突变基因，消除苹果－桔子的问题。这第三种技术－phiC31－在小鼠和人类细胞中也可以发挥功能，提示这种新技术具有通用性。
英文原文：
P(acman) Takes A Bite Out Of Deciphering Drosophila DNA
P(acman) - a new method of introducing DNA into the genome of fruit flies or Drosophila - promises to transform the ability of scientists to study the structure and function of virtually all the fly's genes, and the method may be applicable to other frequently studied organisms such as mice, said its Baylor College of Medicine developers in an article in the current issue of the journal Science.
"P(acman) overcomes a key limitation of currently available methods because it allows you to study large chunks of DNA in vivo," said Dr. Hugo Bellen, professor of molecular and human genetics at Baylor College of Medicine and director of the program in developmental biology. He is also a Howard Hughes Medical Institute investigator. The new technique allows researchers to study large genes and even gene complexes in the fruit fly, which was not possible before.
P/phiC31 artificial chromosome for manipulation, or P(acman), combines three recently developed technologies: a specially designed bacterial artificial chromosome (BAC) that allows maintenance of large pieces of DNA in bacteria, recombineering that allows the manipulation of large pieces of DNA that can then be inserted into the genome of the fly at a specific site using phiC31-mediated transgenesis.
It is a new technique with far-reaching promise, said Bellen.
P(acman) overcomes certain obstacles that have hampered research. It allows the cloning of large pieces of DNA to be used to transform the genome, and it permits that DNA to be inserted into specific places in the genome. Bellen credits the report's first author, Koen J.T. Venken, a graduate student in the BCM Program in Developmental Biology, with putting the technologies together to come up with a new methodology in the field.
Current technology has certain problems for researchers seeking to understand the structure and function of genes, said Bellen. Often, when scientists breed flies that lack a particular gene and then try to put that gene back into the fly, it inserts itself randomly into the genetic blueprint.
In some cases, it makes too much protein, and in others, too little. In other instances, it may disrupt the message from another gene.
"You are really comparing apples and oranges when you do this," said Bellen. The technique is also limited to small DNA chunks.
"Koen set out to develop a new transgenesis system using the three techniques," said Bellen.
The bacterial artificial chromosome, or BAC, he used allows the scientist to maintain large chunks of DNA in the bacteria, but it is present in only one or few copies. However, the bacteria can be induced to produce many copies of the DNA when needed.
Koen then integrated a technique called 'recombineering' into the strategy, which facilitates the scientist to clone large chunks of DNA and subsequently allows them to make specific mutations anywhere he or she wants in the gene.
The third technique allows the researcher to pinpoint where he or she wants to the mutant gene to go in the genetic blueprint of the fly, eliminating the apples-and-oranges problem. This third technique - phiC31 - works also in mouse and human cells, implying that this new technique could be used in those cells as well.
