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.

项目摘要 由细胞主动外排药物引起的多药耐药是临床上抗肿瘤治疗的主要障碍之一。 癌症化疗和传染病的治疗。世界卫生组织的新监测数据 该组织揭示了世界上一些最常见的，潜在的 最危险的病原体，包括那些导致疟疾和呼吸道疾病的病原体， 结核抗药性病原体的威胁日益严重，这使人们看到了一个没有有效药物的世界的前景。 抗生素，使患者容易受到以前可治疗的传染病的影响。多药外排 系统已经发展到保护微生物和人类免受有害的异生物质和有毒代谢物的影响。 它们调节外源性物质的吸收、分布和排泄，并在人体内保护保护组织 通过调节血脑屏障、血胎盘屏障和血睾丸屏障的药物渗透性。此外，本发明还提供了一种方法， 转运蛋白也是决定药物反应的主要参与者，从药理学功效到毒性， 并参与宿主-病原体相互作用。因此，更全面地了解多药外排 系统对于设计更有效的治疗方案以及改善患者预后至关重要。 该提案要求部分支持戈登研究会议（GRC）和戈登 关于多药物外排系统的研究研讨会（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31号这次会议的主要目标是汇集研究人员从两个传统的 分离的领域，原核和真核转运蛋白领域，跨学科工作 （微生物学、化学、药理学、医学和临床研究），相互学习。九 口头报告会议和四个海报会议将促进新科学家之间的科学互动。 研究人员，该领域的领导者，以及在学术界，制药和生物技术领域工作的同事 行业第二个目标是传播技术进步和变革方法。 会议将突出最近的创新，在结构-功能关系的理解，识别 药物结合位点、药物外排机制和转运蛋白的药理学靶向 包括新颖的药物递送策略。长期目标是开发更特异、更强效的药物 抑制、调节或逃避多方面的外排系统。将进一步强调对以下方面的管制： 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， 对特定环境线索的反应。第三个目标是指导早期职业科学家， 来自少数民族背景的妇女和科学家，并提供学习环境和支持系统 这对培养该领域未来的领导者至关重要。总的来说，这次会议将促进在 在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。