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

项目摘要 几乎所有活细胞都使用特异性非酶碳水化合物结合蛋白（例如凝集素）来识别 碳水化合物配体用于细胞运输、信号传导和防御。凝集素及其生物活性的系统研究 碳水化合物配体的发现提高了我们对人类健康的理解， 某些细胞相互作用使它们成为治疗发现的宝贵资源。在以前的研究中， 我的实验室提出，人类肠道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，而不是简单的模式识别所介导的网络 受体和保守的微生物代谢产物。此外，我们对高度普遍的人类的描述- 微生物凝集素Cbeg 5表明这种特异性凝集素可能调节基本的人类骨髓细胞相互作用 是正常微生物组稳态的组成部分。因此，这项建议的中心假设是， Cbeg 5和其他人类微生物凝集素的研究将阐明与人类健康相关的微生物组功能， 其可以被开发用于治疗。我们将通过三个目标来推进这一假设，以定义（1）如何 Cbeg 5调节不同的骨髓细胞群，（2）开发Cbeg 5作为治疗骨髓增生异常综合征的药物的潜力。 炎症性肠病，以及（3）探索由炎症性肠病调节的微生物组相互作用的更大网络 人微生物凝集素。

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.