Clostridium botulinum and neurotoxin core facility

肉毒梭菌(BoNTs)的神经毒素是对人类毒性最大的蛋白质， 都是A类特工。BoNTs(...-150,000 kDa)是一种锌依赖的蛋白水解酶，它包括一种 被指定为A型到G型的七种蛋白质组(A-G)具有相似的AB 结构-功能性质，但具有有限的初级氨基酸同源性。BoNTs引发松弛 通过切割作为贩运和对接一部分的SNARE蛋白而瘫痪 融合囊泡的成分。BONT的B组分与神经元上的受体结合 细胞，产生这种陶醉的滋养。而由A-G血清型引起的麻痹 BONT在临床上是相似的，每种血清型的BONT都在特定的位置切割个别的SNARE蛋白 氨基酸。NIAID已经确定针对BONT的治疗和疫苗的开发是 竞标防御产品的优先级。 这一核心设施将支持第5区域内两个研究提案的研究工作。“ 《肉毒杆菌中毒的疫苗和治疗学》和《随机的纳米流体转导》 BONT的生物分子识别。虽然参与这些提议的研究人员已经 在细菌致病机制的特定方面，约翰逊博士提供了BONT方面的专业知识 生物学和遗传学。该核心设施将“维持肉毒梭菌和 用于遗传学研究的肉毒杆菌的非产毒衍生物；生产和提纯肉毒杆菌；提供 稳定BoNTs以保持高比毒性的专业知识；提供BoNTs和基因 肉毒杆菌和肉毒杆菌的非产毒衍生物提供给RCE成员的材料； 对肉毒杆菌进行遗传接合/转化和重组DNA操作； 生产和提纯肉毒杆菌中突变的BoNT；进行动物研究，包括 小鼠LD50、小鼠挑战和中和分析；以及维护生物安全环境 用于肉毒杆菌和BoNTs的研究。开发这一核心将为 RCE目前的研究工作，并促进未来与BONT研究相关的项目 区域5。

The neurotoxins of Clostridium botulinum (BoNTs) are the most toxic proteins to humans and are Category A agents. BoNTs (..-150,000 kDa) are zinc-dependent proteases that comprise a group of seven proteins designated as serotypes A through G. BoNT(A-G) share similar AB structure-function properties, but possess limited primary amino acid homology. BoNTs elicit flaccid paralysis through the cleavage of SNARE proteins that are part of the trafficking and docking components of fusion vesicles. The B component of BoNT binds to receptors located on neuronal cells, yielding the trophism of this intoxication. While the paralysis elicited by the A-G serotypes of BoNT is clinically similar, each serotype of BoNT cleaves individual SNARE proteins at specific amino acids. NIAID has identified the development of therapeutics and vaccines against BoNT as high priority for biD-defense products. This core facility will support the research efforts of two research proposals within Region 5" "Vaccines and therapeutics against botulism" and "Nanofluidic Transduction of Stochastic Biomolecular Recognition of BoNT". While investigators involved in these proposals have expertise in specific aspects of bacterial pathogenesis, Dr. Johnson provides expertise in BoNT biology and genetics. The core facility will" Maintain strains of Clostridium botulinum and nontoxigenic derivatives of C. botulinum for genetic studies; Produce and purify BoNTs; Provide expertise on stabilization of BoNTs to retain high specific toxicity; Provide BoNTs and genetic materials from C. botulinum and nontoxigenic derivatives of C. botulinum to members of the RCE; Conduct genetic conjugation/transformation and recombinant DNA manipulations on C. botulinum; Produce and purify mutated forms of BoNT in C. botulinum; Conduct animal studies, including mouse LD50s, mouse challenges, and neutralization analyses; and maintain biosafety environment for research with C. botulinum and BoNTs. Developing this core will provide the platform for current research efforts of the RCE and facilitate future projects related to BoNT research within Region 5.