2023 Multi-Drug Efflux Systems: Targeting the Mechanisms and Regulation of Multi-Drug Transporters for Advancing Health during a Pandemic GRC/GRS

2023 多药物外排系统：针对多药物转运蛋白的机制和调节，以在大流行 GRC/GRS 期间促进健康

• 批准号: 10614335
• 负责人: Lauren M Aleksunes
• 金额: $ 0.7万
• 依托单位: GORDON RESEARCH CONFERENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-03 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10614335
• 关键词: Academia; Address; Affect; Anti-Infective Agents; Antibiotic Resistance; Bacteria; Biology; Biotechnology; Blood; Blood-Testis Barrier; Brain; COVID-19 pandemic; Career Choice; Career Mobility; Cells; Cessation of life; Chemistry; Chemotherapy-Oncologic Procedure; Climate; Clinical; Clinical Research; Collaborations; Communicable Diseases; Communities; Computer Models; Creativeness; Cues; Dangerousness; Data; Development; Discipline; Disease; Drug Binding Site; Drug Delivery Systems; Drug Efflux; Drug Interactions; Drug Kinetics; Ensure; Evaluation; Excretory function; Exposure to; Failure; Fertilization; Fostering; Future; Gene Expression; Genomics; Goals; Health; Healthcare; Human; Immune System Diseases; Industry; Infection; International; Knowledge; Leadership; Learning; Left; Machine Learning; Malaria; Malignant Neoplasms; Mechanics; Mediating; Medicine; Mentors; Mentorship; Methods; Microbiology; Mind; Morbidity - disease rate; Multi-Drug Resistance; Mutation; Nature; Oral; Participant; Patient-Focused Outcomes; Patients; Permeability; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Placenta; Postdoctoral Fellow; Proteomics; Public Health; Regulation; Request for Proposals; Research; Research Personnel; Resistance; Resources; Respiratory Disease; Role; Science; Scientific Advances and Accomplishments; Scientist; Structure; Support System; System; Technology; Texas; Tissues; Toxic effect; Training; Tuberculosis; Underrepresented Minority; Woman; Work; World Health Organization; Xenobiotics; absorption; anti-cancer; antimicrobial; career; career development; cellular imaging; comorbidity; cost; design; diarrheal disease; disability; diversity and inclusion; drug resistant pathogen; educational atmosphere; effective therapy; efflux pump; fighting; frontier; global health; graduate student; health disparity; improved; infectious disease treatment; innovation; innovative technologies; meetings; microorganism; minority scientist; molecular imaging; multi drug transporter; multidisciplinary; novel strategies; novel therapeutics; pandemic disease; pathogen; peer; pharmacologic; posters; recruit; response; side effect; single cell analysis; skills; structural biology; success; supportive environment; surveillance data; symposium; therapeutic development; therapy outcome; transcriptomics; virtual

Project Summary Multidrug resistance caused by active drug efflux from cells is one of the major clinical impediments in anti- cancer chemotherapy and treatment of infectious diseases. New surveillance data by the World Health Organization reveals widespread antibiotic resistance in some of the world's most common, and potentially most dangerous, pathogens including those causing diarrheal and respiratory diseases, malaria and tuberculosis. The growing threat of drug-resistant pathogens raises the prospect of a world without effective antimicrobials, where patients are left vulnerable to previously treatable infectious diseases. Multidrug efflux systems have evolved to protect microorganisms and humans from harmful xenobiotics and toxic metabolites. They regulate absorption, distribution, and excretion of xenobiotics, and in humans, protect sanctuary tissues by regulating the drug permeability of the blood-brain, blood-placenta and blood–testis barriers. In addition, transporters are also major players in dictating responses to drugs, from pharmacological efficacy to toxicity, and are involved in host-pathogen interactions. Thus, a more complete understanding of multidrug efflux systems is of paramount important for the design of more effective treatments with improved patient outcomes. This proposal requests partial support for the Gordon Research Conference (GRC) and Gordon Research Seminar (GRS) on Multi-Drug Efflux Systems to be held in Galveston, Texas, March 25 – March 31, 2023. The primary goal of this conferences is to bring together researchers from two traditionally isolated fields, the prokaryotic and eukaryotic transporter fields, working across a variety of disciplines (microbiology, chemistry, pharmacology, medicine, and clinical research), to learn from each other. Nine sessions of oral presentations, and four poster sessions will foster scientific interactions between new investigators, leaders in the field, and colleagues working in academia, the pharmaceutical and biotechnology industries. The second goal is to disseminate technological advances and transformative approaches. Sessions will highlight recent innovations in the understanding of structure-function relations, the identification of the drug binding sites, and drug-efflux mechanics, and the pharmacological targeting of transporters including novel drug delivery strategies. The long-term goal is to develop more specific and more potent drugs that inhibit, modulate or evade the multifaceted efflux systems. Further emphasis will be on the regulation of efflux systems mediated by local and global regulators and the multilayered control of gene expression in response to specific environmental cues. The third goal is to mentor early career scientists, integrate women and scientists from minority backgrounds, and provide a learning environment and support system critical for development of future leaders of the field. Overall, this conference will foster discussions at the frontiers of science in multidrug efflux systems for reversing multidrug resistance and advancing global health.

项目概要 由细胞活性药物流出引起的多药耐药性是抗耐药性的主要临床障碍之一。 世界卫生组织的癌症化疗和传染病治疗的新监测数据。 组织揭示了世界上一些最常见和潜在的抗生素耐药性 最危险的是病原体，包括引起腹泻和呼吸道疾病、疟疾和 耐药病原体日益增长的威胁使世界面临着无效的前景。 抗菌药物，患者容易遭受多种药物外流。 系统已经发展到可以保护微生物和人类免受有害外源物和有毒代谢物的侵害。 它们调节外源物质的吸收、分布和排泄，并在人类中保护庇护组织 此外，通过调节血脑、血胎盘和血睾屏障的药物渗透性。 转运蛋白也是决定药物反应的主要参与者，从药理功效到毒性， 并参与宿主-病原体相互作用，从而更全面地了解多药流出。 系统对于设计更有效的治疗方法和改善患者的治疗效果至关重要。 该提案请求戈登研究会议（GRC）和戈登的部分支持 多药物流出系统研究研讨会 (GRS) 将于 3 月 25 日至 3 月在德克萨斯州加尔维斯顿举行 2023 年 3 月 31 日。本次会议的主要目标是将来自两个传统领域的研究人员聚集在一起 孤立的领域，原核和真核转运蛋白领域，跨多个学科开展工作 （微生物学、化学、药理学、医学、临床研究），相互学习九。 口头报告会议和四场海报会议将促进新学者之间的科学互动 研究人员、该领域的领导者以及学术界、制药和生物技术领域的同事 第二个目标是传播技术进步和变革方法。 会议将重点介绍在理解结构-功能关系、识别 药物结合位点、药物流出机制以及转运蛋白的逻辑药理学靶向 包括新的药物输送策略，长期目标是开发更特异、更有效的药物。 抑制、调节或逃避多方面的外排系统。 由局部和全局调节因子介导的外排系统以及基因表达的多层控制 应对特定环境线索的第三个目标是为早期职业科学家融入导师。 少数民族背景的女性和科学家，并提供学习环境和支持系统 总体而言，本次会议将促进该领域未来领导者的发展。 逆转多药耐药性和促进全球健康的多药外排系统的科学前沿。