Neutrophils and polytrauma - from recruitment to phenotypic and functional reprogramming

中性粒细胞和多发伤 - 从招募到表型和功能重编程

• 批准号: 10797986
• 负责人: SOFIA DE OLIVEIRA
• 金额: $ 24.99万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10797986
• 关键词: Animal Model; Animals; Behavior; Chronic; Diet; Drosophila genus; Genetic; Inflammation; Inflammatory Response; Injury; Knowledge; Lipids; Metabolic syndrome; Modeling; Molecular; Multiple Trauma; Neutrophil Infiltration; Optics; Organ; Pathologic; Patient-Focused Outcomes; Pattern; Phenotype; Play; Predisposition; Process; Proteins; Research; Role; Site; System; Tissues; Transcript; Transgenic Organisms; Trauma; Traumatic injury; Visualization; Work; Zebrafish; epigenetic profiling; genetic manipulation; high risk population; imaging approach; improved; migration; mutant; neutrophil; parent grant; pharmacologic; programs; recruit; response; skills; targeted treatment; tool

Abstract The zebrafish animal model provides a unique opportunity to visualize, track and deconvolute the molecular mechanism involved in the neutrophil response in polytrauma at a whole-animal context. The optical transparency and ease of genetic and pharmacological manipulation of this small vertebrate system has become a powerful tool to study neutrophils and injury, with innumerous key findings in the last decade. Herein we propose to evaluate 1) the regulatory mechanisms that coordinate neutrophil recruitment to concurrent traumatic injuries, 2) how neutrophils are reprogrammed at sites of traumatic injury to generate specific neutrophil subsets that reverse migrate and disseminate inflammation in trauma, and 3) how chronic inflammation impacts such processes. We will combine whole-animal non-invasive live imaging approach with genetic manipulation and protein, lipid, transcript, and epigenetic profiling of neutrophils. Our research will allow us to gain a deeper understanding of the neutrophil mechanisms involved in polytrauma inflammatory response in healthy and metainflammation settings. Our lab has over 120 lines of zebrafish transgenic and mutant lines that allow us to visualize and genetically manipulate neutrophils. A recent detected fruit fly infestation is creating improper conditions that are particularly concerning for our line of work, jeopardizing our research program supported by the parent grant. Moreover, we are also encountering additional space issues that will be limiting our research soon as we expand our program (currently at 95% capacity). Our research program has a unique line of work that aligned with our models, tools and skills will contribute with significant knowledge to the field of polytraumatic injury. This knowledge will enable us to manipulate neutrophil response as a means by which to improve patient outcomes following trauma, particularly in high-risk groups.

摘要