Examination of the mechanism by which the salvador/warts/hippo complex restricts cell growth and number

癌症是一种由多余细胞产生引起的疾病。这些多余的不需要的细胞是由于细胞过度增殖和程序性细胞死亡受损而产生的。由于许多不同基因的突变，这些重要的过程在癌症中可能会被解除控制。在不同类型的癌症中已经报道了许多遗传病变，但在这些疾病中发生突变的许多基因尚未被确定。为了分离出与癌症有关的新基因，我们在果蝇中制造了随机突变，并测试了它们引起实体癌症的能力。果蝇是这项研究的一个很好的模式生物，因为许多在癌症中经常受到干扰的途径在人类和果蝇之间是保守的。通过这种方法，我们确定了几个已知的和新的导致癌症生长的基因。通过研究这些新基因的人类对应物，我们确定了其中一些基因在人类癌症产生中的潜在作用。其中三种基因，河马，萨尔瓦多和疣，似乎共同限制细胞数量。在这项研究中，我们旨在了解这些基因限制细胞数量的机制。为了做到这一点，我们将分析这一途径的活动是如何被控制的，以及它在哪些组织中起作用。我们还计划在河马、萨尔瓦多和疣的下游发现这条通路的其他关键成分。为了进行这些实验，我们将使用各种体外生化技术以及组织培养细胞实验。然后，我们将在整只动物身上验证这些实验的结果。通过进行这些实验，我们希望对癌症的起源有更深入的了解。

Cancer is a disease that results from the generation of surplus cells. These extra unwanted cells are produced as a result of excess cell proliferation and impaired programmed cell death. These important processes can be deregulated in cancers as a result of mutations in many different genes. Many genetic lesions have been reported in different types of cancers but many of the genes that are mutated in these diseases have yet to be identified. To isolate new genes involved in cancer we created random mutations in the vinegar fly, Drosophila, and tested their ability to cause solid cancers. Drosophila is an excellent model organism for this study because many of the pathways that are often perturbed in cancer are conserved between humans and flies. Using this approach we identified several known and novel genes that cause cancerous growths. By studying the human counterparts of these novel genes we identified a potential role for some of these genes in the generation of human cancer. Three of these genes, hippo, salvador and warts, appear to act in concert to restrict cell number. In this study we aim to understand the mechanism by which these genes restrict cell number. To do this we will analyze how the activity of this pathway is controlled and in what tissues it functions. We also plan to discover other key components of this pathway that function downstream of hippo, salvador and warts. To perform these experiments we will use a variety in vitro biochemical techniques as well as experiments in tissue culture cells. We will then verify the results of these experiments in the context of a whole animal. By performing these experiments we hope to gain greater insight into the genesis of cancer.