Glycobiologyand glycomics are the scientific fields that study carbohydrates (sugars) in the cell – their chemical structure, how they’re made, where they’re located, and how they influence protein and cell function. Glycomics is to carbohydrates what genomics is to genes and proteomics is to proteins. Glycobiologists study glycans – carbohydrate chains and carbohydrate-coated proteins – and the proteins that bind them.
Read below for more on glycans, glycan-binding proteins and their roles in human health.
Glycans cover the surface of every living cell – either hanging out by themselves or bound to fats and proteins. Chemical bonds link sugar molecule to sugar molecule, forming complex carbohydrate chains. The different ways these bonds can be arranged leads to the great diversity of glycans.
Cells piece together proteins by following DNA’s recipe, but building a glycan is a bit more complicated. Unlike protein translation, the addition of sugar residues to proteins has no recipe. Instead, genes encode special enzymes that link sugar residues to growing proteins as they are being constructed. This sugar-adding process is extremely specific – each enzyme gathers one particular carbohydrate precursor and adds it to a specific point in the protein at a particular time and place. In a way, sugar-adding enzymes are like assembly line workers lining a conveyer belt, each responsible for adding a sugar as the growing protein moves along through the protein-building pathway.
Making something without a recipe is more complicated, but it also leaves more room for flexibility. There is an incredible diversity in glycan expression from birth, and the glycome of a particular cell, tissue or organism can vary drastically in response to slight changes in any of hundreds of sugar-adding enzymes.
The functions of glycan-binding proteins (GBPs) and glycans go hand-in-hand. Both GBPs and glycans are expressed in virtually every tissue in the body. There, they interact in a variety of ways, sometimes in response to an outside signal such as inflammation or infection. Many GBPs are bound to cell surfaces, with the part that binds glycans extending away from the cell. Some cell surface GBPs also have an internal part that sticks into the cell. With these types of GBPs, binding an extracellular glycan can trigger changes in the intracellular domain that sets off a cascade of reactions in the cell. This series of cellular events can lead to a number of actions, including changes in cell migration, differentiation, growth or cell death. Defining a GBP’s exact preference for a glycan is the first step in exploring its biological function.
Glycobiology and human health
Cellular processes driven by glycans and GBPs can ultimately affect infection, immunity, fertility, cancer, and many other aspects of health and disease.
Within the body, glycans mediate communication between cells. For example, the cells that make up blood vessels express a glycan called P-selectin. During inflammation, these cells pump up P-selectin production. Then, white blood cells rolling by in the bloodstream recognize and bind P-selectin, bringing them to a halt. These immune defense cells are then able to squeeze out of the blood vessel and into the surrounding tissue, where they help clean up the offending infection or injury.
Cells also use glycans to interact with the external environment. Glycans expressed on host cells are recognized and bound by invading microbes. The type of tissue that expresses a microbe’s preferred glycan ligand often determines what part of the body that microbe infects and the type of disease it causes. For example, when Helicobacter pylori, a bacterium that can cause stomach ulcers, encounter the cells lining the stomach, the bacterium induces changes in the expression of cell surface glycans in the stomach in a way that helps it grab hold, the first steps in establishing infection.
Medically speaking, glycans represent an underutilized class of therapeutics, drug targets and disease biomarkers. The study of glycans presents unique challenges that benefit from a systems approach involving many scientific disciplines and methods for cross-referencing information at molecular, cellular, tissue and whole-body levels.
For examples of glycobiology research at Sanford-Burnham, see the following blog posts:
Fresh Recruits at the Immunological Frontlines
La Jolla Collaboration Helps a Young Iranian Girl
New Hope for a Rare Disease
Embracing Nanomedicine, Part 1