Autophagy in Fungal Hyphae - Functional Genomic and Mechanical Strength Studies

自噬(字面意思是“自噬”)最近已经成为生物学中的一个重要话题，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发挥着关键作用。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循环。所涉及的大多数分子成分已经被鉴定出来，并在从酵母到人类的各种物种中高度保守。虽然已经在几种模式生物中研究了自噬，但几乎没有关于丝状真菌自噬的信息。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。虽然病原真菌每年造成无数人死亡和数十亿美元的农作物损失，但用于生物加工行业的真菌每年产生数十亿美元的有益产品。值得注意的是，在上述每一种情况下，自噬似乎都扮演着突出的角色。自噬不仅可能是对营养限制的一种基本反应，而且在这一建议中假设自噬也是丝状真菌中一种正常的、与发育有关的现象，发生在营养丰富的条件下。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。这项提议的广泛目标是发展对与丝状真菌自噬相关的分子和细胞水平现象的基本理解。将对特定基因的功能进行研究，假设这些基因在自噬的启动和调节中发挥作用。因为自噬很可能是所有影响人类的真菌过程中不可或缺的一个方面，所以这里发展的基本理解可能会有广泛的应用。例如，自噬途径的新成分或效应器可能是抗真菌治疗药物设计的有吸引力的候选者。此外，深入了解在生物过程中抑制自噬(部分或全部)的机制可能会提高次生代谢物的生产率。在这两种情况下，财务影响都将是巨大的(每年数十亿美元)。这一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，并将接受尖端技术培训。本科生也将参与研究的方方面面。此外，这里描述的研究将被纳入中学一级的推广单元，加强本科生和中学生的学习。

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.