Explore how Dr. Ryan Weiss utilizes genome-wide CRISPR screening to reveal the regulation of complex carbohydrates, offering new insights into therapeutic targets for glycosylation disorders.
All animal cells contain complex carbohydrates, also known as glycans. These post-translational modifications are covalently linked to proteins and lipids in the extracellular space, serving as essential molecules in cell signaling and development.
Heparan sulfate proteoglycans (HSPGs) are widely expressed on the cell surface and within the extracellular matrix of all animal cells. These glycoproteins are composed of a core protein with one or more covalently linked heparan sulfate (HS) polysaccharide chains consisting of alternating glucosamine and uronic acids that are heterogeneously N- and O-sulfated.
Through their interaction with numerous matrix proteins and growth factors, HSPGs play a crucial role in regulating a number of vital biological processes, including cell proliferation and development.
The arrangement and orientation of sulfated sugar residues in HS determine the specific locations of ligand binding sites on the cell surface. These modifications can vary both spatially and temporally, depending on the tissue or in the context of human diseases.
At present, not much is known about the regulatory mechanisms responsible for the variable composition and binding properties of HS. To address this knowledge gap, genome-wide CRISPR screening assays have been utilized in human cells to uncover pathways involved in controlling HS assembly.
Moreover, novel transcriptional and epigenetic regulators of HS assembly have been identified via in silico analyses of gene promoters involved in HS biosynthesis. Collectively, these studies offer valuable insight into the mechanisms directing HS biogenesis in cells and have the potential to identify therapeutic targets for glycosylation disorders.
Key findings
- CRISPR screening and bioinformatic methods can be utilized to identify new regulatory mechanisms of glycan biosynthesis in human cancers.
- Chromatin remodeling complexes are essential epigenetic regulatory factors involved in controlling the expression of critical genes involved in mammalian glycosylation in human cells.
Keynote speaker
Dr. Ryan Weiss, Assistant Professor, Department of Biochemistry and Molecular Biology Faculty, Complex Carbohydrate Research Center at the University of Georgia
Dr. Ryan Weiss earned his B.S. in Chemistry back in 2008 from Point Loma Nazarene University in San Diego, CA, followed by a Ph.D. in Chemistry in 2015 at the University of California, San Diego, under the supervision of Prof. Yitzhak Tor.
After moving to the Department of Cellular and Molecular Medicine at the University of California, San Diego, Dr. Weiss began working as a postdoctoral fellow in Prof. Jeffrey Esko’s group. In January 2021, he started an independent career as an assistant professor at the Complex Carbohydrate Research Center at the University of Georgia.
His research program is dedicated to understanding the structure, function, and regulation of complex carbohydrates in human biology and disease. The Weiss Laboratory itself also focuses on the development of pharmacological and cell-based tools to streamline the discovery of new therapeutic methods for treating congenital disorders of glycosylation.