Shell Seminar: Systems Glycobiology with Sriram Neelamegham

Many of the complex mechanisms of the human body still remain unknown to researchers. Specifically, the intricate details of protein synthesis linger as a mystery that beckons to be solved. Sriram Neelamegham and a team of researchers from the State University of New York at Buffalo are working on a project to decipher the formation of glycogens in the body; an important study that has several beneficial applications in the health care industry. At its core, the research focuses on examining glycans, which Neelamegham notes are, “functional components of the cell surface.” Glycogens are a type of sugar structure, similar to glucose. However, glucose is monosaccharide while glycogen is polysaccharide, being made up of multiple glucose molecules. Neelamegham emphasizes the use of the engineering perspective in this biochemical project, specifically to break down the chemical reactions that happen inside the cytoplasm of a human cell.

To fully understand how these extended chains of carbohydrates form, Neelamegham made it a point to clarify the process in how cells produce those structures. Essentially ribosomes in the cell act as a, “car factory manufacturing different cars, which are the proteins.” Each drill at the factory is like a single site on the ribosome, which has a unique structure so it will only produce proteins of that shape. While the final structures that are produced can be easily analyzed to see their components, the intermediate steps in how those structures are formed hide in the dark.

By applying systems glycobiology and computer analysis, the Buffalo researchers can peer into the inner workings of the human body and how exactly each, “cog” works. Infinitesimally small probes tag glycopeptides to become “glycoprobes,” and they track the movement and change of individual glycopeptides. Then mass spectrometry data collection quantifiably measures the output of the reaction. The goal researchers hope to get to is to be able to gather sequences of enzymes that can be further studied.

After experimental data has been collected, intricate algorithms can accurately predict the different combinations and permutations of the output glycogens. Each glycopeptide evolves in a tree of intermediate steps of a chemical reaction, which the computer can calculate what to be. This software is surprisingly written in merely a derivative of XML computer code, dubbed “SBML” for systems biology markup language. The software pulls chemical data from the total wealth of chemical compounds known to scientists and can even give names to the different structures discovered. In conclusion, Neelamegham found out that, “while some people study heart attacks in rats to try and stop heart attacks in humans, in turns out that the physiological differences between the two are vast.” In the future, Neelamegham hopes to be able to use glycogen system analysis to find chemicals that can reduce problems such as inflammation, among other issues.