Clostridium botulinum and neurotoxin core facility

肉毒杆菌和神经毒素核心设施

• 批准号: 7700363
• 负责人: Eric A. Johnson
• 金额: $ 16.74万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7700363
• 关键词: Amino Acids; Animals; Binding; Biology; Biomedical Engineering; Bioterrorism; Bontoxilysin; Botulinum Toxin Type A; Botulism; Categories; Cells; Centers for Disease Control and Prevention (U.S.); Chemistry; Cleaved cell; Clinical; Clostridium botulinum; Collaborations; Communicable Diseases; Communities; Core Facility; Development; Devices; Diagnostic; Docking; Emergency Situation; Endopeptidases; Engineering; Environment; Future; Genetic; Genetic Conjugation; Genetic Materials; Human; Individual; Industry; International; Intoxication; Military Personnel; Mus; Mutate; National Institute of Allergy and Infectious Disease; Neurons; Neurotoxins; Paralysed; Pathogenesis; Peptide Hydrolases; Personal Satisfaction; Property; Proteins; Recombinant DNA; Recombinants; Research; Research Personnel; Research Proposals; SNAP receptor; Serotyping; Source; Structure; Support of Research; Toxic effect; Toxin; Universities; Vaccine Therapy; Vesicle; Wisconsin; Zinc; bacterial genetics; botulinum; botulinum toxin type C; experience; member; nanofluidic; pathogen; receptor; repository; response; therapeutic vaccine; trafficking

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.

肉毒梭菌（BONTS）的神经毒素是人类最有毒的蛋白质， 是A类代理。 Bonts（..- 150,000 kDa）是锌依赖性蛋白酶，包括A 指定为血清型A到G的七个蛋白质组。 结构功能特性，但具有有限的原发性氨基酸同源性。 BONTS会引起脆弱的 通过贩运和对接的一部分的圈套蛋白质的裂解 融合囊泡的成分。 BONT的B分量与位于神经元上的受体结合 细胞，产生这种醉酒的营养不良。而瘫痪是由A-G的血清型引起的 BONT在临床上是相似的，每种血清型都在特定的 氨基酸。 NIAID已确定针对BONT的治疗剂和疫苗的开发为 投标防御产品的高优先级。 该核心设施将支持5区5区域内的两项研究建议的研究工作。 “反对肉毒杆菌的疫苗和疗法”和“随机的纳米流体转导 生物分子识别BONT”。而参与这些建议的研究人员则具有 约翰逊博士在细菌发病机理的特定方面方面的专业知识提供了专业知识 生物学和遗传学。核心设施将“保持肉毒梭菌的菌株和 肉毒杆菌的无氧衍生物用于遗传研究；产生并净化底发；提供 稳定BONT的专业知识以保持高特异性毒性；提供BONT和遗传 来自肉毒杆菌的肉毒杆菌和肉毒杆菌的无氧衍生物的材料； 对肉毒杆菌进行遗传结合/转化和重组DNA操作； 在肉毒杆菌中产生并净化突变形式的骨头；进行动物研究，包括 小鼠LD50，小鼠挑战和中和分析；并保持生物安全环境 用于研究肉毒杆菌和BONT。开发此核心将为 RCE的当前研究工作，并促进了与BONT研究有关的未来项目 区域5。