Lipid dynamics and metabolism in microglial function

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Inflammation is normally an immune process intended to protect and repair tissue that has been damaged by infection or injury, however in the brain and spinal cord microglia are specialized immune cells that have adapted inflammatory mechanisms to carry our natural supportive roles. While we are continuing to gain new insights into how microglia carry out their normal functions, there are many questions that have yet to be answered. Two unique features that contribute to microglial function in the brain are: their dynamic behaviour - microglia are capable of changing shape, moving rapidly through brain tissue, and expanding their size to engulf other objects; and their ability to survive in diverse environments - during a stroke microglia survive and function in the absence of blood flow and nutrients while other cells die. In the current proposal we aim to investigate the means by which microglia are capable of such unique functions, focusing on the following specific questions. Question 1 - What mechanisms allow microglia to expand and contract the cell surface while moving through tissue, engulfing material, and undergoing shape transitions? Question 2 - How do microglia process and store lipid material ingested while clearing debris from brain tissue? Question 3 - Can inhibition of lipid storage alter microglial functions and modify natural inflammatory roles? These questions will allow us to address some of the fundamental functions that occur during inflammation of the brain and spinal cord, and in doing so allow us to better understand what causes inflammation to damage healthy tissue during disease or injury.