Characterization of lectins to understand human microbiome functions and develop live biotherapeutics

凝集素的表征以了解人类微生物组功能并开发活生物治疗药物

基本信息

批准号：
10637133
负责人：
Louis Jared Cohen
金额：
$ 37.18万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2028-02-29
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10637133
关键词：
Architecture Bacteria Binding Bioinformatics Biological Response Modifier Therapy Carbohydrates Cell Communication Cell Separation Cells Clinical Trials Colitis Collaborations Complex Data Data Set Dendritic Cells Disease Engineering Environment Functional disorder Future Gene Family Genes Gnotobiotic Grant Health Homeostasis Human Human Microbiome Immune Inflammatory Bowel Diseases Intestines Laboratories Lectin Length Libraries Ligands Macrophage Maintenance Maps Mediating Mucous Membrane Mus Myeloid Cells New York Patients Pattern recognition receptor Peripheral Blood Mononuclear Cell Persons Polysaccharides Population Proteins Regulation Research Research Methodology Resources Role Severities Signal Transduction Site Specificity Target Populations Testing Therapeutic carbohydrate binding protein carbohydrate receptor cellular targeting commensal bacteria commensal microbes dextran sulfate sodium induced colitis effective therapy experimental study functional genomics gut microbiota host-microbe interactions human microbiota improved intestinal homeostasis microbial microbiome microbiome sequencing microbiota monocyte mouse model murine colitis novel therapeutic intervention novel therapeutics pre-clinical protein complex response screening structural biology therapeutic development trafficking

项目摘要

Project Summary Almost all living cells use specific non-enzymatic carbohydrate binding proteins (e.g. lectins) to recognize carbohydrate ligands for cellular trafficking, signaling and defense. The systematic study of lectins and their carbohydrate ligands has improved our understanding of human health and the high specificity of lectins for certain cellular interactions has made them a valuable resource for therapeutic discovery. In previous research, my laboratory suggested that human commensal microbiota utilize lectins (e.g. human-microbial-lectins) to regulate a complex network of host-microbe interactions beyond those mediated by simple pattern recognition receptors and conserved microbial metabolites. Furthermore, our characterization of a highly prevalent human- microbial-lectin Cbeg5 suggests this specific lectin may regulate fundamental human myeloid cell interactions integral to normal microbiome homeostasis. As such, the central hypothesis of this proposal is that the study of Cbeg5 and other human-microbial-lectins will elucidate microbiome functions relevant to human health and which can be developed therapeutically. We will advance this hypothesis through three aims to define (1) how Cbeg5 regulates distinct myeloid cell populations, (2) the potential to develop Cbeg5 as a therapeutic for inflammatory bowel disease, and (3) to explore the larger network of microbiome interactions regulated by human-microbial lectins.

项目概要几乎所有活细胞都使用特定的非酶碳水化合物结合蛋白（例如凝集素）来识别用于细胞运输、信号传导和防御的碳水化合物配体。凝集素及其作用的系统研究碳水化合物配体提高了我们对人类健康和凝集素的高度特异性的了解某些细胞相互作用使它们成为治疗发现的宝贵资源。在之前的研究中，我的实验室建议人类共生微生物群利用凝集素（例如人类微生物凝集素）调节宿主-微生物相互作用的复杂网络，超越简单模式识别介导的网络受体和保守的微生物代谢物。此外，我们对高度流行的人类的描述微生物凝集素 Cbeg5 表明这种特定的凝集素可能调节基本的人类骨髓细胞相互作用正常微生物组稳态不可或缺的一部分。因此，该提案的中心假设是该研究 Cbeg5 和其他人类微生物凝集素的研究将阐明与人类健康和相关的微生物组功能可以通过治疗来开发。我们将通过三个目标来推进这一假设，以定义（1）如何 Cbeg5 调节不同的骨髓细胞群，(2) 开发 Cbeg5 作为治疗药物的潜力炎症性肠病，以及（3）探索更大的微生物组相互作用网络人类微生物凝集素。