Regulation of Fungal Invasive Growth

描述(由申请人提供)：本研究项目调查 真菌生物体侵入性生长的调控。在哺乳动物中，有能力 侵袭正常组织屏障是转移性癌症的重要特征 细胞和发育中的胚胎中的细胞。相比之下，在成人中， 与底物的调节相互作用控制细胞的增殖和 细胞凋亡。这种底物的调节在恶性疾病中通常是缺失的。 转型。这项研究的目标是了解监管 与底物的相互作用。真菌白色念珠菌和酵母菌 酿酒酵母将被用作模型系统，因为真菌细胞也相互作用 有底物的。在机会性病原体白念珠菌中，与 底物在促进生物体的侵袭性生长方面可能是重要的。 在宿主的组织内。因此，对白色念珠菌侵袭性生长的研究将 也有助于理解起着重要作用的过程 在疾病中。 白色念珠菌对底物存在的反应是通过产生侵袭性的 丝状菌丝，可穿透到基质中。白色念珠菌的培养 周围基质中的细胞促进菌丝的快速产生。遗传 对这一过程的分析导致了两种基因产物的鉴定 这是正常的菌丝生产所需的，以响应周围的基质。 酿酒酵母对底物的存在也会通过 侵入性生长，尽管在这种有机体中，入侵与 形态上的戏剧性变化。酿酒酵母与白色念珠菌的同源物 上述基因是正常侵入性生长所必需的。因此，研究 将在酿酒酵母中进行，以开发详细的分子 关于基因功能的假说。对白色念珠菌的研究将测试 在酿酒酵母中发展的假设的一般性。实验是 建议确定与感兴趣的基因产物结合的相互作用子和 阐明这些基因产物参与的途径。

DESCRIPTION (provided by applicant): This research project investigates the regulation of invasive growth in fungal organisms. In mammals, the ability to invade normal tissue barriers is an important attribute of metastatic cancer cells and of cells in the developing embryo. In contrast, in the adult regulatory interactions with the substratum control cell proliferation and apoptosis. This regulation by substratum is commonly lost upon malignant transformation. The goal of this research is to understand regulatory interactions with substratum. The fungi Candida albicans and Saccharomyces cerevisiae will be used as model systems because fungal cells also interact with substratum. In the opportunistic pathogen, C. albicans, interactions with the substratum may be important in promoting invasive growth of the organism within the tissues of a host. Thus, studies of C. albicans invasive growth will also contribute to the understanding of a process that plays an important role in disease. C. albicans responds to the presence of substratum by producing invasive filamentous hyphae, which penetrate into the matrix. Culture of C. albicans cells within surrounding matrix promotes rapid production of hyphae. Genetic analysis of this process has led to the identification of two gene products that are needed for normal hyphal production in response to surrounding matrix. S. cerevisiae also responds to the presence of substratum by undergoing invasive growth, although, in this organism, invasion is not associated with a dramatic change in morphology. S. cerevisiae homologues of the C. albicans genes described above are needed for normal invasive growth. Therefore, studies in S. cerevisiae will be performed in order to develop detailed molecular hypotheses for the function of the genes. Studies in C. albicans will test the generality of the hypotheses developed in S. cerevisiae. Experiments are proposed to identify interactors that bind to the gene products of interest and to elucidate the pathways in which these gene products participate.