Artificial Golgi Created With Sugars

Sugars not only are the basic ingredient of a person's diet but are also the most vital and complex molecules in the human body.

An undergraduate student at Rensselaer Polytechnic Institute has created artificial Golgi apparatus from sugars.

Graduating senior Jeffery Martin has utilised his basic lessons on sugars to create a lab-on-a-chip device that builds complex, highly specialized sugar molecules, that mimics one of the most important cellular structures in the human body - the Golgi Apparatus.

"Almost completely independently he has been able to come closer than researchers with decades more experience to creating an artificial Golgi. He saw a problem in the drug discovery process and almost instantly devised a way to solve it," said Robert Linhardt, the Ann and John H. Broadbent Jr. '59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer and Martin's adviser.

The Golgi Apparatus, which looks like a stack of pancakes under a microscope, is used by the cells to build sugars. It completes the process of protein synthesis by decorating the proteins with highly specialized arrangements of sugars, and the final molecule is then sent out into the cell to aid in cell communication and to help determine the cell's function in the body.

The new artificial Golgi functions in a similar way to the natural Golgi, but Martin's chip looks similar to a miniature checker board where sugars, enzymes, and other basic cell materials are suspended in water and can be transported and mixed by applying electric currents to the destination squares on the checker board.

This process may enable the sugars to be built in an automated fashion where they are exposed to a variety of enzymes found in the natural Golgi. The resulting sugars can then be tested on living cells either on the chip or in the lab to determine their effects.

Martin said that the chip's ability to process many combinations of sugars and enzymes could enable researchers to quickly develop new sugar-based drugs.

It's long been known that certain sugars, like heparin, can serve as extremely beneficial therapeutics for humans. Heparin, one of the most widely used drugs in the world, is formed naturally in the Golgi organelle in cells of the human body, and in animals like pigs. Heparin acts as an anticoagulant preventing blood clots, which makes it a good therapeutic for heart, stroke, and dialysis patients.

Currently, the main source of heparin is the intestines of foreign livestock, from which the risk of contamination is high. Thus, researchers are trying to develop a safer, man-made alternative to the drug that will prevent outside contamination. Martin said that a synthetic alternative would build the sugar from scratch, helping eliminate the possibility of contamination.

"I am very grateful to have the privilege of working with Dr. Linhardt who has discovered the recipe to make fully synthetic heparin. Because we know the recipe, I am going to use it as a model to test the device. If our artificial Golgi can build fully functional heparin, we can then use the artificial organelle to produce many different sugar variants by altering the combination of enzymes used to synthesize them. Another great thing about these devices is that they are of microscale size, so that if needed we could fill an entire room with them to increase throughput for drug discovery," Martin said.

The study indicates that millions of possible sugar combinations can be formed and scientists only know the function of very few of them like heparin. This artificial Golgi can help in developing sugar-based drugs, called glycotheraputics. Martin hopes that further research may even hep them to find a sugar whose signal blocks the spread of cancer cells.

Source-ANI
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