Researchers at the Technion, Israel Institute of Technology, have developed an innovative technology that utilizes light to remotely manage a unique process that controls the entering Calcium into the cell. It could give people the ability over how they feel pain and how much and where their immune system reacts.
Calcium is an essential mineral for human health. Although its effects on bone density are particularly well-known, it serves a far larger purpose in the human body. Calcium is a “messenger” that conveys messages between cells and plays a crucial role in processes that regulate gene expression in immune cells, muscular contraction, and electrical transmission in the nervous system, among many other bodily activities. A complex system has developed during evolution to control how much calcium is in each cell. This is because abnormal changes in calcium levels in cells are likely to cause many diseases.
Professor Raz Palty of the Rappaport Faculty of Medicine has spent many years studying a central process called store-operated calcium entry that nearly all types of cells use in order to control the levels of their internal calcium stores.
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When this regulation system stops working, the clinical consequences can be catastrophic, including serious harm to the function of T cells, which are an essential part of the immune system.
“The store-operated calcium shuttling system in the cell has been researched for many years,” explained Prof. Palty, who conducted the research together with Dr. Ronald Udasin and Dr. Elia Zomot. “But since this is a highly complex system that generates different calcium signals in different types of cells and also works alongside other calcium entry mechanisms, in a ‘noisy’ environment, it is often very hard to study the role of this cellular machinery under normal physiological settings in which cells are exposed to their native agonists.”
The researchers published in PNAS describes the breakthrough in establishing a technology that allows exact spatial and temporal regulation of calcium entrance into cells.
Prof. Palty’s research group has worked on this challenge, using a number of methodologies from chemistry, biology, and physics to address this difficulty, in collaboration with the research groups headed by Professor Yuval Shaked of the Technion, Faculty of Medicine, and Professor Michael Kienzler of the University of Connecticut.
The researchers developed a reversible optical switch that allows them to regulate when and where medications delivered into the body become active. In this method, they are able to regulate the amount of calcium that enters the cell at the appropriate time and location. Using this technique, the study team was able to modulate calcium entry into T cells and regulate the generation of essential cytokines for immune system function.
Moreover, in a series of experiments conducted in collaboration with a research team led by Professor Alex Binshtok of the Hebrew University of Jerusalem, the researchers discovered that store-operated calcium shuttling machinery is also active in the perception of pain, suggesting that manipulating this machinery may facilitate a more precise understanding of pain transmission mechanisms. The purpose of the follow-up study is to further the researchers’ understanding of these regulatory systems and expand the therapeutic uses of the technology they have built.