Light-Based Protein Manipulation Within Living Cells

protein research cell physiology

In an exciting break-through from the Institute for Basic Science in South Korea, researchers have developed a new method by which light can manipulate proteins to inactivate them within living cells. The ability to target and manipulate specific proteins without the use of drugs is predicted to be a key feature in the future of cancer biology research.

Though the human genome contains only 20,000-25,000 genes it is estimated that those genes have the potential to produce over two million different types of proteins. Some of these proteins are essential to life while others can be thought of as accessories or even clutter that the cell produces. Though quite a few of these proteins have received considerable attention from the scientific community, other proteins and their role within the human body remain a complete mystery.

Until this point, most of what is known about the function of proteins has come from genetic studies. Specifically, genes for a particular protein are identified and subsequently mutated, inhibited or enhanced. The resulting effects on the cells, tissues, and/or organism are observed, and any changes can be attributed to the protein for which that gene coded. But not all proteins can be studied in this way. Some proteins are so critical to an organism’s development that turning off the gene for that protein would result in the death of that organism before the protein’s effects could be observed in a mature adult. Still other methods using small molecule drugs have been used to study protein function in adult organisms, but their effects usually impact the organism globally and are therefore not useful for studying a protein’s specific localized function.

New technology developed from South Korea’s Institute for Basic Science promises to speed up and enhance the study of protein functions. They call their new method “Light-Activated Reversible Inhibition by Assembled Trap” or “LARIAT” for short. The new system acts by first linking the specific protein in question with green fluorescent protein (GFP). The GFP-protein complex can in turn be linked to cryptochrome 2 (CRY2). In the presence of blue light and yet another protein, CIB1, CRY2 forms dense clusters. Consequently, any GFP-protein complex bound to the clumping CRY2 is also dragged into the dense protein clusters. This crowded environment causes whatever proteins were originally tagged with GFP to become inactivated. The process is also reversible, which means that researchers can selectively inactivate proteins within living cells to better understand that specific protein’s physiological role(s).

To prove the concept of their work, the team from South Korea demonstrated their new technique by selectively shutting off proteins that are essential to cell migration and cell division. Attempting to study such proteins by the traditional method of shutting off the corresponding genes would have resulted in the pre-mature termination or incomplete formation of an experimental organism.

This innovation represents a huge advancement for multiple fields of biology and health sciences. The development can be thought of as analogous to the discovery of RNAi, which has since allowed researchers to turn off individual genes to analyze their effects within an organism. Already members of the IBS team are applying the new LARIAT technology to examine the physiological roles of different proteins in the animal brain and in relation to cancer metastasis.

By Sarah Takushi

Sources

AsianScientist.com
InnovateUs Inc
Nature Methods 
PBS

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