Integration of appendage and Hox networks during Drosophila development

了解动物身体图案的遗传控制是马哈菲实验室的长期目标。HOX基因是体型的主要调节者，它规定了所有动物沿体轴的前后解剖结构。Hox基因编码转录因子，这些转录因子激活下游基因，这些下游基因是沿着身体前后轴正常发育所需的基因。然而，目前还不清楚特定的Hox蛋白如何调控不同的下游基因，因为它们都与目标基因中的相似DNA序列结合。同样，这种高度保守的因素是如何产生在自然界中观察到的动物身体形式的多样性的，目前还不清楚。明确的是，这些基因在不同物种中指定了相似的身体部位，当在错误的组织中缺失表达时，也会导致发育缺陷和癌症。有了这个奖项，马哈菲实验室将以果蝇黑腹果蝇为模式生物，研究Hox蛋白如何与其他转录因子结合，以确定身体模式。果蝇已被证明是生物医学研究的优秀模型。在他们的研究中，马哈菲实验室采取了双管齐下的方法。其中一个依赖于在果蝇中开发的广泛的遗传工具来发现由HOX基因调控发育的分子过程。另一种是采用一种不那么标准的群体遗传学方法进行系统生物学研究。通过这种方式，他们希望扩大已知的Hox蛋白的功能，以及它们如何整合到支配动物发育的基因网络中。虽然上面提到了这项工作的医学相关性，但这个奖项将为本科生甚至高中生，除了研究生之外，提供参与和了解科学研究的机会。

Understanding the genetic control of animal body patterning is the long-term goal of the Mahaffey laboratory. Hox genes are master regulators of body pattern, specifying anterior-posterior anatomical structures along the body axis of all animals. The Hox genes encode transcription factors that activate downstream genes required for proper embryonic development along the anterior-posterior body axis. However, it is not clear how specific Hox proteins regulate distinct downstream genes because they all bind to similar DNA sequences in their target genes. Likewise, it is not clear how such highly conserved factors generate the diversity of animal body forms observed throughout nature. What is clear is that these genes specify similar body parts in diverse species and also contribute to developmental defects and cancers when miss-expressed in the wrong tissues. With this award, the Mahaffey lab will study how Hox proteins integrate with other transcription factors to specify body patterns, using the fruit fly, Drosophila melanogaster as a model organism. Drosophila has proved to be an excellent model for biomedical research. In their studies, the Mahaffey lab is taking a two-pronged approach. One relies on the extensive genetic tools developed in the fruit fly to discover molecular processes of developmental regulation by Hox genes. The other involves taking a less-standard, population genetics approach for systems biological studies. In this manner, they hope to extend what is known about the function of Hox proteins and how they integrate into the network of genes governing animal development. While medical relevance of this work has been mentioned above, this award will provide opportunities for undergraduate and even high school students, in addition to graduate students, to have an opportunity to participate in and learn about scientific research.