Gene Expression During Sporulation

描述（由申请人提供）：本提案侧重于枯草芽孢杆菌如何形成孢子。枯草芽孢杆菌已成为研究孢子形成和原核生物细胞分化的范例，因为它易于遗传操作。枯草芽孢杆菌孢子形成的所有关键调节因子也存在于其他孢子形成物种中，包括致病菌炭疽芽孢杆菌、破伤风梭菌、产气荚膜芽孢杆菌、肉毒杆菌和艰难梭菌，它们分别是炭疽、破伤风、气性坏疽、肉毒杆菌中毒和结肠炎的病因。高抗性的孢子对这些物种在自然界的生存至关重要。枯草芽孢杆菌研究的结论将对这些物种具有普遍的有效性。孢子的形成包括分裂成两种不同的细胞类型，母细胞和孢子前。前孢子被母细胞吞没，发育成成熟孢子。孢子的形成需要四种RNA聚合酶因子的作用。F然后呢？在pre - spore和？然后呢？K在母细胞中。它提出了发育生物学的一个基本问题：基因表达如何与形态变化协调？该提案解决了这个问题。什么时候？f定向信号从孢子中激活？母细胞中的E被延迟，采取了一种新的发育途径，即在一个母细胞内形成两个孢子。这种行为开启了染色体复制和生长是如何在孢子形成过程中受到控制的研究。它有助于研究同一种群中基因相同的生物体如何遵循不同的发育路径。F激活后染色体易位进入孢子前。有人建议研究易位的完成如何导致母细胞吞噬前孢子和激活？G在被吞没的孢子中。公共卫生相关性：本建议关注枯草芽孢杆菌孢子形成过程中基因表达与形态变化如何协调的基本问题。在相关病原体中也发现了所有关键的产孢调控基因，包括炭疽芽胞杆菌、破伤风梭菌、产气荚膜芽胞杆菌、肉毒杆菌和艰难梭菌。重点放在如何改变信号的时间可以改变所采取的发展路径。

DESCRIPTION (provided by applicant): This proposal focuses on how spores are formed by Bacillus subtilis. B. subtilis has become a paradigm for the study of spore formation, and of cell differentiation in prokaryotes, because of the ease of its genetic manipulation. All the key regulators of B. subtilis spore formation are also found in other spore forming species including the pathogens B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile, the causes of anthrax, tetanus, gas gangrene, botulism and colitis following antibiotic therapy, respectively. The highly resistant spores are critical to the survival of theses species in nature. Conclusions from a study of B. subtilis will have general validity for these species. Spore formation involves a characteristic division into two different cell types, the mother cell and the prespore. The prespore is engulfed by the mother cell and develops into the mature spore. Spore formation requires the action of four RNA polymerase factors, ?F and then ?G in the prespore and ?E and then ?K in the mother cell. It presents a fundamental problem of developmental biology: how is gene expression coordinated with morphological change? The proposal addresses this problem. When the ?F-directed signal from the prespore to activate ?E in the mother cell is delayed, a novel developmental path is taken, in which two spores are formed within one mother cell. This behavior opens up the proposed study of how chromosome replication and growth are controlled during sporulation. It facilitates a study of how genetically identical organisms in the same population can follow different developmental paths. Translocation of the chromosome into the prespore follows activation of ?F. It is proposed to study how completion of translocation leads to engulfment of the prespore by the mother cell and activation of ?G in the engulfed prespore. PUBLIC HEALTH RELEVANCE: This proposal focuses on the fundamental problem of how gene expression is coordinated with morphological changes during formation of spores by Bacillus subtilis. All the key sporulation regulatory genes are also found in related pathogens, including B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile. Emphasis is placed on how altering the timing of signaling can change the developmental path taken.