Establishment of a Genetic System in Candida albicans

超出所提供的空间。白色念珠菌是一种二倍体真菌，随着医疗水平的提高，它已成为主要的医院病原菌；高度衰弱和免疫抑制的病人。近年来，在利用分子遗传学探索这种生物体的毒力机制方面取得了巨大进展，但由于其二倍体的性质和明显缺乏性循环，严重阻碍了对这种重要病原体的了解，因为在inS上进行了这种优雅的实验。酿酒是不可能的。我们最近构建了能够交配的白色念珠菌菌株，我们也发现临床分离的很大一部分在MIL位点是纯合子的（aor a），因此可能能够在体内交配。在这个提议中，我们有三个具体的目标：1)我们将描述交配反应，检查其遗传基础，以最大限度地提高其对研究者的有用性，并了解其在念珠菌生物学中的作用。2)我们将寻找在交配产物中产生减数分裂的条件，以便完成性循环。如果我们在我们的交配产物中没有发现减数分裂，我们将利用我们对酿酒酵母减数分裂的了解来构建应该能够减数分裂的菌株。3)我们将询问是否交配和减数分裂可以在非实验室菌株中发生，我们将检查MTLa， MTLa和MIL a/a（二倍体和四倍体）菌株在体内的行为，看看是否有性循环的部分或全部成分发生在动物身上。这项拨款提出的实验将开启念珠菌生物学的新纪元，并将允许研究人员对这种有机体的发病机制提出新的重要问题。如果我们能找到或设计出一种方法使四倍体的交配产物恢复到二倍体，那么白色念珠菌将会对所有在酿酒念珠菌中开发的重要技术开放，这些技术使这种真菌成为选择的模式系统。但是对于念珠菌，我们研究的不是模型系统而是病原体本身。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Candida albicans is a diploid fungus which has becomeamajornosocomialpathogen as improved medical carehas preserved the live; of highly debilitated and immunosuppressed patients. In recent yearsgreatadvanceshavebeen madein the use of molecular genetics to probe the mechanisms of virulence in this organism, but its diploid nature and apparent lack of a sexualcyclehave seriously hampered advances in understanding this important pathogen, since elegant experiments of the sort carried out inS. cerevisiae havebeen impossible. Wehaverecently constructedstrains of C.albicans that will mate, and we havealso found that a significant fraction of clinical isolates are homozygous(aor a)at the MIL locus andthus maybe able to matein vivo. In this proposal we havethree specific aims: 1)Wewill characterize the mating reaction, examining its genetic basis in order to maximize its usefulness to investigators aswell asto understand its role in the biology of Candida. 2)We will search for conditions which will give rise to meiosis in the mating products so that the sexualcycle will becompleted. If wefail to find meiosis in our mating products, wewill useour understanding of meiosis in S.cerevisiaeto construct strains which ought to be capable of meiosis. 3) Wewill ask whether mating and meiosis can occur amongnon-laboratory strains and wewill examine the behavior of MTLa, MTLa, and MIL a/a(both diploid andtetraploid) strains in vivo, to seewhether some or all of the components of the sexualcycle occur in the animal. Theexperiments proposed in this grant will open a newera in Candidaalbicans biology and will allow investigators to formulate newand important questions about the pathogenesis of this organism. If we canfind or devise away to return the tetraploid mating products to diploidy, C.albicans will beopen to all the important technology developed in S.cerevisiae,technology which hasmadethat fungus the model systemof choice. But with Candida, we will be studying not a model systembut the pathogen itself. PERFORMANCE SITE ========================================Section End===========================================