Regulation of transcriptional responses to intercellular signaling during development

我的研究计划的主要目标是了解细胞如何随着动物的发育而变得专门化。这种特化过程涉及打开一些基因、关闭其他基因的机制，最终，这种基因活动的图谱会导致每个细胞采用允许其在组织内履行其功能的形状、功能和/或行为。大多数组织由许多不同类型的细胞组成，这些细胞类型通常被组织成非常特定的空间模式。这种模式反映了每个单个细胞检测其在组织中的位置并适当调节其基因的能力。 我实验室的工作重点是了解发育中的组织中的每个细胞如何感知自己的位置，接收生物化学指令来指导其专门化，以及为其位置和未来功能打开和关闭正确的一组基因。通过研究发育中的果蝇卵巢作为模型组织，我们最近发现，存在于组织不同区域的生化信号可以产生复杂而特定的基因活性模式。在它们重叠的地方，它们一起工作来开启和关闭基因。我们现在建议进一步研究这些信号是如何协作的，以及它们如何选择激活和抑制哪些基因的细节。 果蝇的基因实际上与人类非常相似，超过75%的果蝇基因与人类相似。这种相似性表明，我们通过研究果蝇获得的遗传学教训将告诉我们许多关于人类和其他动物的基因是如何调控的。

The broad goal of my research program is to understand how cells become specialized as an animal develops. This specialization process involves mechanisms that turn some genes on turn others off, and ultimately this profile of gene activity leads each cell to adopt the shape, function, and/or behaviour that allows it to fulfill its function within the tissue. Most tissues are made up of a number of different types of cells, and these multiple cell types are often organized into very specific spatial patterns. Such a pattern reflects the ability of each individual cell to detect where it lies within the tissue and regulate its genes appropriately. The work in my lab is focused on understanding how each cell in the developing tissue senses its position, receives biochemical instructions to guide its specialization, and turns on and off the correct set of genes for its position and future function. By studying the developing fruit fly ovary as a model tissue, we recently discovered that complex and specific patterns of gene activity can be generated by biochemical signals that are present in different regions of the tissue. Where they overlap, they work together to turn genes on and off. We now propose to further study how these signals collaborate, as well as the details of how they choose which genes to activate and which to inhibit. The genes of the fruit fly are actually very similar to those of humans, and over 75% of fruit fly genes have a recognizable human equivalent. This similarity suggests that the genetic lessons that we learn by studying the fruit fly will tell us a lot about how genes are regulated in humans and other animals.