Glycosylation and the Transgenic Plants
What is glycosylation, you may ask? Is it a process, a part of a plant, or even an artificial machine? No, but rather it's a mechanism that is performed by plants that is very crucial to understanding my project. Glycosylation is an enzymatic, site-specific process that takes place around the endoplasmic reticulum where a carbohydrate molecule is added to a target protein. In this sense, the carbohydrate helps to stabilize a protein's structure, allowing the protein to fold correctly. Another purpose for glycosylation is that it helps immune cells to be able to recognize host cells by developing sugar-binding proteins called lectins. These lectin proteins are what allow the immune cells to recognize other host cells by recognizing specific carbohydrate molecules, that are found on the surface of all host cells. As you can see clearly, this property is very important for a healthy immune to function property and not end up becoming an autoimmune disease.There are five different classes of glycosylation and they include: N-linked glycosylation, O-linked glycosylation, phosphor-linked glycosylation, c-linked glycosylation, and glypiation. For the development of the monoclonal antibodies at the Biodesign Institute, the researchers utilize N-linked glycosylation to change the structure of the Fab region of the antibodies. The Fab region of an antibody is the portion of the antibody that locks or hooks onto a specific cell surface for which in the case of antibodies is what allows the antibodies to opsonize a particular pathogen.
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| Here are the three regions that make up an antibody. |
Hence, as you can see by changing the structure of the antibodies the researchers at the Biodesign Institute are altering the role of these proteins so that they can opsonize the specific Dengue virus. If I haven't mentioned it before, what I mean by opsonization is that it's an immune defense process where antibodies specific to a particular virus can surround the entire virus surface and hook onto the virus' surface receptors, keeping the virus from being able to infect a host cell and replicating. This ability to alter the structure of an antibody is very crucial to my project and is key to unlocking a new alternative to treating pathogens such as the Dengue virus.
At the Biodesign Institute, researchers modify the N-glycosylation process that normally occurs in the Nicotiana benthamiana plants. Usually N-glycosylation requires a special lipid called dolichol phosphate to help attach a nitrogen molecule from asparagine with the glycan, a regular carbohydrate molecule found in plants. N-glycosylation is very unique because normally this enzymatic process occurs in the lumen, which is a network of membrane tubules and vesicles that are responsible for the production of hormones, of the endoplasmic reticulum in eukaryotes. This process is responsible for the folding of many eukaryotic glycoproteins and the cell-extracellular matrix attachment. However at the Biodesign Institute, N-glycosylation to enable proteins in the lab plants to produce the desired antibodies. Normally, since the plants are receiving genetic material from several other bacterial\virus species\strains the plant's immune molecules would attack the foreign cells\viruses. Due to our work at the Biodesign Institute, we were able to modify the glycoproteins' structure found on the surfaces of the introduced bacterial cells and viruses in order to mask their foreign identity from the plant and mammalian immune systems. Somehow by modifying N-glycosylation researchers are able to change the structure of the antibodies, that would be produced from the plants, so that these antibodies appear mammalian-like. As you can see these antibodies like the bacterial cells\virions will be able to float around a host's immune system and perform its duty without being detected by the host's immune system and being destroyed. Overall, the main job researchers want from N-glycosylation is for genetically modified antibodies to be synthesized that can be undetected from both the plants' and mammalian' immune systems.
That is the end to this blog but stay tune to news about the data collected from the antibody quantity produced from the Nicotiana benthamiana plants.
At the Biodesign Institute, researchers modify the N-glycosylation process that normally occurs in the Nicotiana benthamiana plants. Usually N-glycosylation requires a special lipid called dolichol phosphate to help attach a nitrogen molecule from asparagine with the glycan, a regular carbohydrate molecule found in plants. N-glycosylation is very unique because normally this enzymatic process occurs in the lumen, which is a network of membrane tubules and vesicles that are responsible for the production of hormones, of the endoplasmic reticulum in eukaryotes. This process is responsible for the folding of many eukaryotic glycoproteins and the cell-extracellular matrix attachment. However at the Biodesign Institute, N-glycosylation to enable proteins in the lab plants to produce the desired antibodies. Normally, since the plants are receiving genetic material from several other bacterial\virus species\strains the plant's immune molecules would attack the foreign cells\viruses. Due to our work at the Biodesign Institute, we were able to modify the glycoproteins' structure found on the surfaces of the introduced bacterial cells and viruses in order to mask their foreign identity from the plant and mammalian immune systems. Somehow by modifying N-glycosylation researchers are able to change the structure of the antibodies, that would be produced from the plants, so that these antibodies appear mammalian-like. As you can see these antibodies like the bacterial cells\virions will be able to float around a host's immune system and perform its duty without being detected by the host's immune system and being destroyed. Overall, the main job researchers want from N-glycosylation is for genetically modified antibodies to be synthesized that can be undetected from both the plants' and mammalian' immune systems.
That is the end to this blog but stay tune to news about the data collected from the antibody quantity produced from the Nicotiana benthamiana plants.
It's so cool how genetically modified elements work! Despite being undetectable, will there be some sort of consequence from these 'nonnatural' antibodies? Are we able to see the long term effects?
ReplyDeleteHi Victoria great question. Umm so far I don't know if there are any effects that these antibodies pose in a mammalian immune system. Like I said in one of my blogs these antibodies possess mammalian molecule-like structures found in their Fc regions that allow these antibodies to evade the mammalian immune system. So far the long term effects of these antibodies are not known yet. This research is pretty new, so that is why these antibodies haven't been used for "vaccinations" of humans yet. There is a lot of testing that has to do with these antibodies in lab mice, before the researchers can determine if these antibodies can cause long term negative consequences in humans
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