Carolyn Bertozzi (UC Berkeley) Part 1: Chemical Glycobiology

Science Communication Lab

23 Mar 201047:44

EducationalLearning

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TLDRCarolyn Bertozzi's iBioLecture 'Chemical Glycobiology' explores the intersection of chemistry and biology focusing on sugars' biological roles. She discusses the surprising discovery of the limited number of human genes and how post-translational modifications, particularly glycosylation, contribute to biological complexity. Bertozzi delves into the dynamic glycome, its changes during cell differentiation and disease, and the clinical implications, such as potential cancer detection. She also highlights the role of sugars in inflammation and the development of anti-inflammatory drugs, emphasizing the importance of understanding glycobiology in treating human diseases.

Takeaways

🧬 Carolyn Bertozzi is a professor and researcher at UC Berkeley and HHMI, focusing on Chemical Glycobiology, the study of sugars' roles in biological systems.
🌟 The field of glycobiology emerged from the discovery of a limited number of genes in organisms, suggesting that biological complexity arises from post-translational modifications, including glycosylation.
📚 Glycosylation is a complex post-translational modification where sugars are added to proteins, often occurring on the cell surface, affecting cell interactions and functions.
🍬 The human body contains a dynamic 'glycome', the complete set of glycans produced by cells, which can change with the cell's physiological state, including during disease.
🔬 Glycans are synthesized from simple monosaccharide building blocks within cellular organelles like the endoplasmic reticulum and Golgi apparatus.
📐 The structures of glycans are highly diverse and complex, involving various linkages and stereochemistry, which differ from the linear structures of DNA, RNA, and proteins.
🩸 Blood types in humans are determined by the glycan structures present on the surface of red blood cells, a discovery with significant implications for medicine and immunology.
🦠 Influenza virus infection and its potential to cause pandemics are linked to the virus's interaction with host cell surface sugars, particularly sialic acid.
💊 The understanding of the role of sugars in the influenza virus lifecycle led to the development of antiviral drugs like Relenza and Tamiflu, which inhibit the neuraminidase enzyme.
🚑 Inflammation and associated diseases involve the interaction of white blood cells with the endothelial cells lining blood vessels, a process that includes selectin-mediated cell adhesion and sugar binding.
🛡️ The development of multivalent inhibitors targeting selectins and their sugar ligands, such as sialyl Lewis x, represents a potential therapeutic approach to treating inflammatory diseases.

Q & A

What is the field of Chemical Glycobiology?
-Chemical Glycobiology is the study that combines chemistry and biology to understand the role of sugars in biological systems, particularly in the human body.
Who is Carolyn Bertozzi and what is her area of expertise?
-Carolyn Bertozzi is a professor of Chemistry and Molecular and Cell Biology at the University of California at Berkeley, and an investigator of the Howard Hughes Medical Institute. She is a chemist by training with a specialization in the biology of sugars, known as glycobiology.
What was the surprising discovery about the yeast genome that influenced the understanding of eukaryotic organisms?
-The surprising discovery about the yeast genome was that it contains only about 6,000 genes, which was a much smaller number than previously estimated, challenging the idea that more complex organisms require more genes.
Why was the number of genes in the human genome surprising?
-The number of genes in the human genome was surprising because it was only around 25,000, much smaller than the early estimates of over 100,000 genes, indicating that complexity in organisms is not solely determined by the number of genes.
What is the term used to describe the totality of glycans produced by a cell?
-The term used to describe the totality of glycans produced by a cell is 'glycome'.
How do glycans contribute to the complexity of organisms despite the relatively small number of genes?
-Glycans contribute to the complexity of organisms through post-translational modifications of proteins, allowing for a diverse range of biological functions beyond what is encoded in the genome.

Outlines

00:00

🌟 Introduction to Chemical Glycobiology

Carolyn Bertozzi, a professor and investigator, introduces the iBioLecture on Chemical Glycobiology. She explains her background in chemistry and her interest in the biology of sugars, or glycobiology, which she developed during her graduate studies. Bertozzi's research at UC Berkeley aims to integrate chemistry and biology to uncover the roles of sugars in the human body. She discusses the surprising findings from the sequencing of various genomes, including the human genome, which revealed fewer genes than expected, suggesting a reliance on post-translational modifications, such as glycosylation, to generate biological complexity. Glycosylation is highlighted as a significant post-translational modification, with glycoproteins and glycolipids playing crucial roles on the cell surface.

Mindmap

Keywords

💡Chemical Glycobiology

Chemical Glycobiology is the study of the chemistry underlying the biology of sugars. It is a multidisciplinary field that combines chemistry and biology to understand the role of sugars in biological processes. In the video, Carolyn Bertozzi, a chemist turned glycobiologist, discusses her interest in how sugars interact within the human body, highlighting the importance of glycobiology in understanding complex biological systems.

💡Glycosylation

Glycosylation refers to the process of attaching sugar molecules, or glycans, to proteins. This post-translational modification is a key concept in the video as it is one of the most complex ways proteins can be modified, leading to increased biological complexity. Glycosylation is particularly significant on the surface of cells, where it affects cell-cell interactions and is implicated in various diseases.

💡Glycoproteins

Glycoproteins are proteins that have sugar molecules, or glycans, covalently attached to them. In the script, glycoproteins are mentioned as being located on the surface of cells, playing a crucial role in cell-cell recognition and signaling. They are part of what gives cells their 'sugar coating', which is central to the theme of the video.

💡Glycolipids

Glycolipids are lipids with one or more sugar molecules attached. They are components of cell membranes and contribute to the cell's 'sugar coating'. The script mentions glycolipids in the context of the cell membrane, emphasizing their role in the cell's interaction with its environment.

💡Glycans

Glycans, also known as carbohydrates, are complex sugar molecules that are attached to proteins or lipids. They are the focus of glycobiology and are highlighted in the video as critical for understanding the diverse roles sugars play in biological systems, including their dynamic changes in response to cell states.

💡Glycome

The glycome is the complete collection of all glycans produced by a cell. It is analogous to the genome (all genes) or the proteome (all proteins). The script discusses the dynamic nature of the glycome, which changes in response to physiological changes in the cell, such as during development or disease.

💡Monosaccharides

Monosaccharides are the simplest form of carbohydrates and serve as the building blocks for more complex glycans. In the video, monosaccharides like glucose are described as the starting point for the biosynthesis of glycans within the cell, emphasizing their foundational role in glycobiology.

💡Glycosyltransferases

Glycosyltransferases are enzymes that catalyze the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. The script explains their importance in the assembly of glycans within the endoplasmic reticulum and Golgi apparatus, which is central to the understanding of glycan biosynthesis.

💡Sialic Acid

Sialic acid is a type of monosaccharide that often caps the outer ends of glycans on the cell surface. It is highlighted in the script for its unique structure and role in various biological processes, including its involvement in human blood group determination and viral recognition.

💡Inflammation

Inflammation is the body's response to harmful stimuli and is characterized by pain, heat, redness, swelling, and loss of function. In the video, inflammation is discussed in the context of leukocyte recruitment and its role in various diseases. The script explores how sugars and selectins are involved in the inflammatory process, which is a key aspect of understanding glycobiology's relevance to human health.

💡Selectins

Selectins are a family of cell adhesion molecules involved in the binding of leukocytes to endothelial cells, a process crucial in inflammation. The script discusses selectins in relation to their binding to specific sugar structures on the cell surface, illustrating their importance in the glycobiology of inflammation and potential as therapeutic targets.

Highlights

Carolyn Bertozzi, a professor at UC Berkeley and HHMI investigator, combines chemistry and biology to study the role of sugars in the human body.

The yeast genome sequencing revealed approximately 6,000 genes, fewer than expected, challenging the assumption that more complex organisms require more genes.

The human genome was found to contain around 25,000 genes, suggesting biological complexity arises from post-translational modifications like glycosylation.

Glycosylation, the attachment of sugars to proteins, is a significant post-translational modification, often occurring on cell surface proteins and lipids.

Glycoproteins and glycolipids give cells a 'sugar coating', which is dynamic and changes with the cell's physiological state.

The term 'glycome' describes the total glycans produced by a cell, which is dynamic and can indicate cellular changes or diseases.

Glycans are synthesized from simple sugars like monosaccharides through a series of metabolic pathways in the cell.

There are nine monosaccharide building blocks in vertebrate glycans, each with unique names and abbreviations.

Glycan structures are more complex than other biopolymers due to variable linkages, branching, and stereochemistry.

Glycosyltransferases are enzymes that build glycans from monosaccharide building blocks in the ER and Golgi compartments.

The discovery of the human blood groups in the mid-20th century was a significant milestone in glycobiology, impacting transfusion medicine and immunology.

Influenza virus infection and its prevention through vaccines are linked to glycobiology, as the virus uses sugars for host cell attachment.

The development of antiviral drugs like Relenza and Tamiflu targeting neuraminidase in the influenza virus is a practical application of glycobiology.

Inflammation and its associated diseases are linked to the interaction of leukocytes with endothelial cells, involving selectin family proteins and glycans.

Multivalent inhibitors that mimic the display of sugars on cells have potential as broad-spectrum anti-inflammatory drugs.

Glycans play a critical role in physiological processes and diseases, and understanding their molecular contributions can lead to new therapeutics.

Transcripts

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