Autophagy in Fungal Hyphae - Functional Genomic and Mechanical Strength Studies

自噬（字面意思是“自我进食”）最近已经成为生物学中的一个重要课题，因为它在细胞发育，衰老，许多人类疾病和营养限制期间的生存中起着关键作用。自噬也被称为II型程序性细胞死亡，涉及细胞大分子甚至整个细胞器的再循环。大多数涉及的分子组分已被确定，并高度保守的物种，从酵母到man. While自噬已在几个模式生物进行了研究，几乎没有信息是在丝状真菌自噬。这有点令人惊讶，因为丝状真菌对人类活动的影响是巨大的。虽然致病真菌每年造成大量死亡和数十亿美元的作物损失，但生物加工行业中使用的真菌每年生产数十亿美元的有益产品。值得注意的是，在每一种情况下，自噬似乎都起着重要作用。自噬不仅可能是对营养限制的基本反应，而且在该提议中假设自噬也是在营养丰富的条件下发生的丝状真菌中的正常的发育相关现象。因此，自噬很可能对大多数与人类相关的真菌过程产生重大影响。本提案的广泛目标是对与丝状真菌自噬相关的分子和细胞水平现象进行基本了解。将研究特定基因的功能，假设在自噬的启动和调节中发挥作用。 由于自噬可能是影响人类的所有真菌过程的一个组成部分，因此这里开发的基本理解可能具有广泛的应用。例如，自噬途径的新组分或效应物可能代表抗真菌治疗剂设计的有吸引力的候选物。此外，深入了解生物过程中抑制自噬（部分或完全）的机制可能会导致次级代谢产物的生产力增加。在这两种情况下，财政影响将是巨大的（数十亿美元/年）。这项研究也将对人力资本产生广泛的影响。 博士水平的研究生将在跨学科的环境中进行研究，并将接受尖端技术的培训。本科生也将参与研究的各个方面。此外，这里所述的研究将纳入中学一级的外联单元，加强本科生和中学学生的学习。

Marten0519080Autophagy (literally 'self-eating') has recently emerged as an important topic in biology, as it plays a key role in cellular development, aging, numerous human diseases and survival during nutrient limitation. Also called type II programmed cell death, autophagy involves recycling of cellular macromolecules and even whole organelles. Most of the molecular components involved have been identified and are highly conserved in species ranging from yeast to man. While autophagy has been studied in several model organisms, almost no information is available on autophagy in filamentous fungi. This is somewhat surprising, as the impact of filamentous fungi on human activity is enormous. While pathogenic fungi are responsible for numerous deaths and billions of dollars in crop damage each year, fungi used in the bioprocessing industry produce billions of dollars in beneficial products annually. Notably, in each of these cases, autophagy appears to play a prominent role. Not only is autophagy likely to be a fundamental response to nutrient limitation, it is hypothesized in this proposal that autophagy is also a normal, developmentally related phenomenon in filamentous fungi that occurs in nutrient rich conditions. Thus, autophagy is likely to have a significant impact on most of the fungal processes related to man.The broad goal of this proposal is to develop a fundamental understanding of both molecular and cellular level phenomena associated with filamentous fungal autophagy. The function of specific genes, hypothesized to play a role in initiation and regulation of autophagy, will be studied. Because autophagy is likely to be an integral aspect of all fungal processes that affect humans, the fundamental understanding developed here is likely to have broad application. For example, novel components or effectors of the autophagy pathway may represent attractive candidates for the design of antifungal therapeutics. Furthermore, insight into mechanisms that suppress autophagy (either partially or completely) in bioprocesses may lead to increased productivity of secondary metabolites. In both cases, the financial impact would be enormous (billions$/yr). This research will also have broad impact on human capital. PhD level graduate students will conduct research in a cross-disciplinary environment and will be trained in cutting edge techniques. Undergraduates will also be involved in all aspects of the research. In addition, research described here will be incorporated in secondary level outreach modules, enhancing learning for both undergraduates and secondary level students.