Sweet discoveries: unraveling the complex world of sugars in health and disease

Lectures: 1 session / week, 2 hours / session

Recommended prerequisites are:

7.05 General Biochemistry

7.06 Cell Biology

7.08J Biological Chemistry II

Glycans, which are complex assemblies of sugars, are the most prevalent class of macromolecules, surpassing nucleic acids, proteins and lipids. Glycans are essential for life, as they are a required energy source, provide protection against cellular stresses and shape cellular structure. Glycans display vast chemical and structural diversity, which has hampered their discovery and characterization. For example, the molecular basis for organ rejection was not understood until the 1950s, when researchers discovered that glycans are a major component of blood group antigens. Over 50% of proteins in a human cell are modified with one or more glycans. Given the ubiquity of glycans, it comes as no surprise that alterations of glycan metabolism and the cellular glycan profile can have drastic effects on cellular processes and can lead to a class of inborn diseases called congenital disorders of glycosylation.

In addition, the surfaces of viruses and bacteria are extensively decorated with glycans, which can participate in both immunity recognition and evasion. During this course, we will explore the many roles glycans play in human health and disease. For example, we will learn about the healthy glycosylation patterns of many mammalian proteins and the dynamic changes that glycan structures undergo during early development and cancer metastasis, the influence of dietary carbohydrates on glycan metabolism, and the role of densely glycosylated proteins involved in HIV infectivity.

Concurrently, we will learn about the chemical and biological techniques used to detect and visualize glycans by in vitro and whole-animal metabolic labeling approaches, how to profile protein-glycan interactions using high-throughput glycan arrays, and about the development of new carbohydrate-based therapeutics and vaccines to target HIV, influenza and bacterial pathogens. The course will focus on the primary research literature, and we will learn practical laboratory techniques, experimental design and how to interpret data and critique the conclusions offered by authors. Students will have the opportunity to attend a seminar related to the field of glycobiology.

This class will meet once a week for two hours. Each week, we will focus on a different aspect of glycobiology by discussing two papers that highlight that week's topic. We will begin the course with an introduction to the importance of glycans (sugar molecules) in biological processes. We will briefly talk about the early identification of glycans using the breakthrough discovery of glycans as blood group determinants.

Next we will introduce the topics of the subsequent weeks to give a broad overview of the diverse topics of the course. Importantly, we will go over the general format of original research articles and present strategies to help understand and analyze the key findings. Before each class all students should have carefully read the two papers assigned to that week so that they will be able to discuss the contents in detail. We will spend the last 15 minutes of every class introducing the next week's topic (hand-outs will be distributed). During class, students should be engaged in discussion about the two papers, and participation from every student is required. In addition to weekly submission of questions, students are required to submit a mid-semester written assignment and make an oral presentation during the last class.

The class is graded on a pass / fail basis, and grades will be based on participation in discussion every week, satisfactory completion of the written and oral assignments, and attendance.

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