The Biology of Microglia: Adenosine A3 Receptor Suppression

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Microglia are immune cells that reside within the confines of the brain and spinal cord. Previously assumed to be merely support cells for neurons, it is now clear that microglia have many important roles: they are sculptors that shape the cellular architecture of the developing and mature nervous system, electricians that modify neuronal circuitry, and guardians that protect the brain and spinal cord. How microglia undertake these different tasks is not well understood. My research and training program focuses on understanding the fundamental biology of microglia and the core processes that control activity of these cells. We recently made the exciting discovery that microglia are regulated by adenosine A3 receptors (A3R) - these receptors keep microglia activity in check. The proposed research dissects the essential steps in A3R signaling (`the nuts and bolts') and the impact on how microglia communicate with other cells. Experiments will also examine the machinery by which A3R controls activity of the transcription factor Runx1 and the process that drives A3R-mediated release of interleukin-10, a key microglia signaling molecule. We will use advanced biochemical, molecular, and imaging approaches to deconstruct how A3R controls microglia function. This new knowledge will have direct implications for understanding microglia communication, and form a conceptual framework for broader understanding of microglia biology throughout the central nervous system. At the core of this proposed research is the training of highly qualified individuals who will become future leaders in academia, government, and industry.