Measuring Phagosomal Temperatures

测量吞噬体温度

• 批准号: 8796150
• 负责人: David M. Underhill
• 金额: $ 20.88万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8796150
• 关键词: Address; Adipose tissue; Area; Bacteria; Bathing; Biochemical; Biochemical Reaction; Biochemistry; Biological; Biological Process; Body Temperature; Bone Marrow; Brown Fat; Caustics; Cell physiology; Cells; Computer software; Data; Dendritic Cells; Dependence; Detection; Eating; Environment; Enzymes; Equilibrium; Health; Heating; Host Defense; Image; Imaging Techniques; Individual; Ions; Label; Laboratories; Leukocytes; Ligands; Lung; Lymphoid; Mammals; Maps; Measurement; Measures; Mechanics; Methodology; Methods; Microbe; Microscope; Mitochondria; Molecular and Cellular Biology; Muscle Cells; Myelogenous; Peptide Hydrolases; Peritoneal; Phagocytes; Phagocytosis; Phagolysosome; Phagosomes; Physiology; Positioning Attribute; Process; Production; Protocols documentation; Quantum Dots; RNA; Reactive Oxygen Species; Regulation; Reporter; Rest; Role; Shivering; Signal Transduction; Skin; Source; Speed; Structure; Surface; System; Techniques; Temperature; Testing; Thermometers; Thinking; Time; Tissues; Variant; antimicrobial; base; enzyme activity; innovation; killings; macrophage; neutrophil; novel; particle; response; tool

DESCRIPTION (provided by applicant): Do intracellular temperature gradients regulate cellular functions? It is fundamental to our understanding of biochemistry that enzymatic reactions are temperature-dependent, yet we tend to presume that intracellular temperature gradients, if they occur at all, must be dissipated so quickly as to be inconsequential. We hypothesize that intracellular temperature gradients may be as significant as ion gradients (e.g. Ca++ or pH) in regulating cellular functions. The challenge in addressing this question is to establish methodology for measuring meaningful changes in temperature at the subcellular level and to identify a biological process in which the role of this hypothesized temperature regulation can readily be assessed. We are developing methodology for measuring subcellular temperature changes in macrophages and applying these measurements to the process of phagocytosis, a process that strongly activates the cells and one in which degradative enzymes are enlisted to kill potentially threatening microbes. Preliminary data presented demonstrate that significant "Phagosomal Heating" occurs. The project is innovative in that intracellular temperature variations have not yet been implicated as important for regulating cellular functions. With this project, we intend to add a novel method of signaling to our understanding of molecular and cellular biology regulatory mechanisms. The approaches developed will be applicable to all areas molecular and cellular biology.

描述（由申请人提供）：细胞内温度梯度是否调节细胞功能？对于我们对生物化学的理解至关重要，酶促反应是温度依赖性的，但是我们倾向于假定必须如此迅速地消散细胞内温度梯度，以至于无关紧要。我们假设细胞内温度梯度在调节细胞功能中可能与离子梯度（例如Ca ++或pH）一样重要。解决这个问题的挑战是建立方法，以测量亚细胞水平上温度的有意义变化，并确定可以轻松评估该假设温度调节的作用的生物学过程。我们正在开发测量巨噬细胞中细胞下温度变化并将这些测量的方法应用于吞噬作用过程，该过程强烈激活细胞，并将降解酶杀死潜在威胁的微生物。提出的初步数据表明，发生了重要的“吞噬体加热”。该项目具有创新性，因为细胞内温度的变化尚未与调节细胞功能有关。在这个项目中，我们打算为我们对分子和细胞生物学调节机制的理解添加一种新颖的信号传导方法。所开发的方法将适用于分子和细胞生物学的所有领域。