Discovering new compounds to treat global infectious disease

发现治疗全球传染病的新化合物

基本信息

批准号：
8443165
负责人：
Emily R Derbyshire
金额：
$ 9万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443165
关键词：
Address Africa Antimalarials Antiparasitic Agents Area Asia Award Biological Assay Biological Process Biology Blood Cessation of life Chemicals Communicable Diseases Complement Country Culicidae Development Disease Drug Targeting Drug resistance Enzymatic Biochemistry Enzymes Focus Groups Genes Genetic Goals Health Hepatocyte Human Image In Vitro Infection Infectious Diseases Research Integration Host Factors Knock-out Learning Libraries Life Liver Malaria Methodology Molecular Parasites Pharmaceutical Preparations Phase Plasmodium Positioning Attribute Process Proteins Public Health Reporting Research Research Personnel South America Staging Testing Therapeutic Time Training Transgenic Organisms Tropical Disease Work World Health Organization base drug discovery drug mechanism global health high throughput screening in vivo inhibitor/antagonist insight interest medical schools neglect novel parasite invasion programs public health relevance research study screening skills small molecule small molecule libraries tool

项目摘要

DESCRIPTION (provided by applicant): Current estimates from the World Health Organization suggest that global cases of infectious disease are rising. Malaria remains a devastating disease in poor and undeveloped countries in Africa, South America and Asia, where nearly one million deaths were reported in 2009. In these areas, parasites can rapidly develop drug resistance, which erodes the efficacy of antimalarials. Thus new drugs and the identification of novel targets are desperately needed to treat malaria. My graduate studies with Prof. Michael Marletta (UC Berkeley) involved detailed mechanistic studies on enzymes that are important to human health. To learn more about infectious disease and chemical biology I joined Prof. Jon Clardy's lab at Harvard Medical School (HMS). At HMS I received training to work with both the blood and liver stages of the malaria parasite. This training allowed me to develop a high-throughput screen to identify inhibitors of liver stage malaria. In the next two years I plan o screen several small molecule libraries for potential therapeutics to treat malaria (Specific Aim 1). During my time at HMS I will also train with several experts to learn how to generate genetic knockouts in malaria, raise drug resistant parasite strains, and maintain transgenic mosquito lines. I can then use this training to evaluate the biological processes of the parasite that my identified liver stage malaria inhibitors target (Specific Aim 2) and to biochemically characterize the protein targets (Specific Aim 3). The training needed to address Specific Aims 2 and 3 will be completed at HMS during the K99 phase of the award, but most of the experiments will be completed during the independent phase of the award. I plan to apply for a tenure-track academic position with the goal of leading a research group focused on characterizing essential processes and proteins of the malaria parasite that facilitate the disease process. HMS is ideally suited for the proposed K99 training period as it has a state-of-the-art high- throughput screening facility and is a leader in infectious disease research with programs like the Harvard Malaria Initiative. I believe the courses and training I receive in the next two years will broaden my understanding of parasite biology and nicely complement my previous skills in enzymology to make me uniquely suited to work on global infectious disease as an independent researcher.

描述（由申请人提供）：世界卫生组织目前的估计表明，全球传染病病例正在上升。在非洲、南美洲和亚洲的贫穷和不发达国家，疟疾仍然是一种毁灭性的疾病，据报道，2009 年有近一百万人死亡。在这些地区，寄生虫会迅速产生耐药性，从而削弱抗疟药的功效。因此，治疗疟疾迫切需要新药和新靶标的确定。我与 Michael Marletta 教授（加州大学伯克利分校）一起进行的研究生学习涉及对人类健康重要的酶的详细机制研究。为了了解有关传染病和化学生物学的更多信息，我加入了哈佛医学院 (HMS) Jon Clardy 教授的实验室。在 HMS，我接受了疟原虫血液阶段和肝脏阶段的培训。这次培训使我能够开发出高通量筛选来识别肝期疟疾的抑制剂。在接下来的两年中，我计划筛选几个小分子库，寻找治疗疟疾的潜在疗法（具体目标 1）。在 HMS 期间，我还将与几位专家一起接受培训，学习如何在疟疾中进行基因敲除、培养耐药寄生虫菌株以及维持转基因蚊子系。然后，我可以使用此培训来评估我确定的肝期疟疾抑制剂针对的寄生虫的生物过程（具体目标 2），并进行生化表征蛋白质目标（具体目标 3）。解决具体目标 2 和 3 所需的培训将在奖励的 K99 阶段在 HMS 完成，但大多数实验将在奖励的独立阶段完成。我计划申请终身教职学术职位，目标是领导一个研究小组，重点研究促进疾病进程的疟疾寄生虫的基本过程和蛋白质。 HMS 非常适合拟议的 K99 培训期，因为它拥有最先进的高通量筛查设施，并且是传染病研究领域的领导者，其项目包括哈佛疟疾倡议等。我相信未来两年我所接受的课程和培训将会拓宽我对寄生虫生物学的理解很好地补充了我以前在酶学方面的技能，使我非常适合作为一名独立研究员从事全球传染病的工作。