Translating the glycosylation code
Anabel Gonzalez–Gil always viewed science as bland memorization until she began a high school chemistry class.
“I had a professor that was very creative and we had a lot of experiments that were hands on,” she said. “That really caught my attention.”
Channeling that passion, Gonzalez–Gil studied chemistry at Florida International University. As an undergraduate, she spent a summer at the University of Colorado working with calcium-sensing probes.
“That was the first time I did molecular biology and that kind of shifted my career,” she said, explaining she was captivated by being able to modulate protein expression and function.
Following a postbaccalaureate program at the National Institute on Aging, she began graduate school at Johns Hopkins University and was introduced to glycosylation, a type of post-translational modification where combinations of sugars (glycans) are added to proteins or lipids.
Most cell-surface and secreted proteins in the human body are glycosylated. The structure and density of glycans on these proteins regulate receptor binding and downstream cell signaling. Gonzalez–Gil’s doctoral work focused on the immune system, studying the receptor Siglec-8 and its glycosylated ligands in the airway.
Now as a postdoctoral fellow at Johns Hopkins, Gonzalez–Gil investigates the role of glycosylation in the brain. In the future, she plans to open her own lab.
As Gonzalez–Gil reflected on her path, she emphasized the importance of teamwork in pushing science forward. “The best of my career has not been me doing things on my own,” she said. “I would like to highlight how important and how satisfying it is to be able to collaborate.”
Linking a ligand to neurodegeneration
Glycosylation is not static. The sugar groups added to a protein or lipid can be changed quickly to elicit a different cellular reaction. The quintessential example of this rapid adaptation can be seen in the immune system. While the body must engage the inflammatory response quickly to fight a pathogen, it also needs to shut down this pathway after the threat has passed.
Anabel Gonzalez–Gil’s research focuses on Siglecs, a family of receptors primarily found on immune cells. Many human Siglecs bind glycosylated ligands, launching a signaling cascade to downregulate the immune system. In recent years, Siglecs were linked to cancer cells’ evasion of the immune system and Alzheimer’s disease.
“I’m truly fascinated by the ability of glycans to modulate cellular responses in such a short time,” Gonzalez–Gil said. “If you want a different target and outcome, you just have to modify a protein’s glycans.”
She compares this process to work at a construction site. “You don't have to break down the entire house and then take the blocks and build it back up to how you want it,” she said. “You just remodel what needs to be fixed so that it can work better.”
Gonzalez–Gil and colleagues in at the Johns Hopkins University School of Medicine discovered a glycosylated version of the protein RPTPζ that specifically binds two Siglecs on microglia, the immune cells of the brain. Their research showed that RPTPζ expression is elevated in the brains of patients diagnosed with Alzheimer’s.
The team now is working to understand the link between RPTPζ and the inflammation associated with neurological diseases, Gonzalez–Gil said.
“We are really focusing on trying to understand how the production of this ligand fine-tunes the immune system.”
was published in the Journal of Biological Chemistry in June 2022. Gonzalez–Gil and other winners of the JBC Tabor Award will give talks during a symposium on Sunday, March 26, at Discover BMB in Seattle.
Enjoy reading ASBMB Today?
Become a member to receive the print edition four times a year and the digital edition monthly.
Learn moreGet the latest from ASBMB Today
Enter your email address, and we’ll send you a weekly email with recent articles, interviews and more.
Latest in People
People highlights or most popular articles
Meet the 2025 SOC grant awardees
Five science outreach and communication projects received up to $1,000 from ASBMB to promote the understanding of molecular life science.
Unraveling cancer’s spaghetti proteins
MOSAIC scholar Katie Dunleavy investigates how Aurora kinase A shields oncogene c-MYC from degradation, using cutting-edge techniques to uncover new strategies targeting “undruggable” molecules.
How HCMV hijacks host cells — and beyond
Ileana Cristea, an ASBMB Breakthroughs webinar speaker, presented her research on how viruses reprogram cell structure and metabolism to enhance infection and how these mechanisms might link viral infections to cancer and other diseases.
Understanding the lipid link to gene expression in the nucleus
Ray Blind, an ASBMB Breakthroughs speaker, presented his research on how lipids and sugars in the cell nucleus are involved in signaling and gene expression and how these pathways could be targeted to identify therapeutics for diseases like cancer.
In memoriam: William S. Sly
He served on the Â鶹´«Ă˝É«ÇéƬ and Â鶹´«Ă˝É«ÇéƬ Biology Council in 2005 and 2006 and was an ASBMB member for 35 years.
ASBMB committees welcome new members
Members joined these committees: Education and Professional Development, Maximizing Access, Meetings, Â鶹´«Ă˝É«ÇéƬ, Public Affairs Advisory, Science Outreach and Communication, Student Chapters and Women in Biochemistry and Â鶹´«Ă˝É«ÇéƬ Biology.