Deciphering the immunoregulatory network governing antigen presenting myeloid cells

破译控制抗原呈递骨髓细胞的免疫调节网络

基本信息

批准号：
10792697
负责人：
Michael W Lipscomb
金额：
$ 22.97万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2027-05-31
项目状态：
未结题

项目摘要

SUMMARY The goal of this administrative supplement for the parent award R35GM145290 is to purchase a flow cytometric analyzer system for high-throughput automated sample acquisition and analysis. The equipment will allow measurement of multiple properties within various investigated immune cell subsets. Readout indices include assessment of cell population frequencies, proliferation capacities, variances in lineage commitment and differentiation, altered molecular signaling activities and changes in functional outcomes in response to pathogen challenges, among other measurements. Briefly, dendritic cells (DC) are responsible for directing T cell responses and macrophages important for modulating tissue inflammation. A hallmark of these immune cells is their inherent plasticity in gene expression profiles to govern immunity vs. tolerance. However, much remains unknown regarding the complex molecular networks that collectively govern hematopoiesis, inflammation and antigen presentation. Incomplete understanding presents major obstacles to delineating their underlying roles in health and disease, which has also hindered success in developing effective immunotherapies. The long-term goal of the proposed research is to determine how pivotal immunoregulatory proteins govern DC and macrophage differentiation and immune responses in steady-state vs. disease settings. Acquisition of a flow cytometric analyzer with a universal loader will allow the laboratory to engage in high-throughput automated sample acquisition to assess multiple indices within samples employing 96- and 384-well plates. Knowledge gained in our studies, with the chief readout instrument being flow cytometric analysis, will fill key gaps in our understanding of DC and macrophage biology and provide important insights into the molecular networks governing immunity and tolerance.

概括家长奖励 R35GM145290 的此行政补充的目标是购买流量用于高通量自动化样品采集和分析的细胞分析仪系统。该设备将允许测量各种研究的免疫细胞亚群中的多种特性。读数指数包括评估细胞群体频率、增殖能力、谱系承诺的差异和分化、分子信号活动的改变以及功能结果的变化除其他测量外，还包括病原体挑战。简而言之，树突状细胞 (DC) 负责指导 T 细胞反应和巨噬细胞对于调节组织炎症很重要。这些免疫的一个标志细胞的基因表达谱具有固有的可塑性，以控制免疫与耐受。然而，很多关于共同控制造血作用的复杂分子网络仍然未知，炎症和抗原呈递。不完整的理解给描绘它们带来了重大障碍在健康和疾病中的潜在作用，这也阻碍了成功开发有效的免疫疗法。拟议研究的长期目标是确定关键的免疫调节如何蛋白质控制稳态与疾病状态下 DC 和巨噬细胞的分化和免疫反应设置。购买带有通用装载机的流式细胞分析仪将使实验室能够从事高通量自动化样品采集，采用 96- 和 384 孔板。在我们的研究中获得的知识，主要的读数仪器是流式细胞术分析，将填补我们对 DC 和巨噬细胞生物学理解的关键空白，并提供重要的见解进入控制免疫和耐受性的分子网络。