Alex Guseman
University of California-San Diego, CA·Biochemistry·Early-career
Every human cell is wrapped in a dense coat of sugars, called glycans, that other proteins read like a surface code. These sugar structures help the immune system tell friend from foe, guide newly made proteins into the right shape, and let cells stick to one another.
- Fields
Biochemistry
Biophysics
Microbiology & Immunology
- Topics
glycans
glycobiology
lectins
- Grants
- 2 known grants, through Jul 2031
What they work on
- Define the thermodynamic and atomic-level structural basis of protein–glycan binding, explaining how a protein picks out one sugar structure from the heterogeneous mixture present on cells.
- Engineer lectins (sugar-binding proteins) with precise glycan specificities using phage display, a library screening method, and use them to decode the molecular grammar of sugar recognition and as probes for defined glycoforms.
- Test how nonspecific crowding within the glycocalyx, the cell's sugar coat, alters protein stability and folding, using newly developed on-cell nuclear magnetic resonance methods and biolayer interferometry.
- Determine the mechanism by which the antiviral lectin BOA blocks SARS-CoV-2 entry, combining viral inhibition assays, biophysical binding measurements and electron microscopy of the glycosylated spike protein.
- Test whether BOA inhibits SARS-CoV-2 variants of concern carrying spike mutations linked to immune escape, and whether it blocks entry of other human beta-coronaviruses.
More about the research
When the code is misread or altered, the consequences show up in cancer, diabetes and transplant rejection. Yet how a protein picks out one sugar from a crowded, chemically similar mixture is still largely unknown at the level of atoms. Work here combines structural biophysics, protein engineering and virology to write down the rules of sugar recognition and then use those rules to build sugar-binding proteins with chosen targets.
Why it matters
Sugar coats on cells and viruses are involved in infection, immune disorders and cancer, but the lack of rules for how proteins read them limits both diagnosis and drug design. Defining those rules and building lectins with chosen specificities could yield new probes and reagents, while the coronavirus work could produce a broad-spectrum entry inhibitor active across variants and related viruses.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Thomas Gallagher
Loyola University Chicago, IL·Microbiology & Immunology
Determine how mutations in the S2 fusion segment of the SARS-CoV-2 spike control the receptor-binding domain and its engagement with receptors, identifying specific variant substitutions that alter receptor reactivity and spike stability.
David Veesler
University of Washington, WA·Microbiology & Immunology
Characterize how broadly serum antibodies from nonhuman primates immunized with nanoparticle vaccines co-displaying multiple receptor-binding-domain and spike antigens bind and neutralize betacoronaviruses.
Hideki Aihara
University of Minnesota, MN·Biochemistry
Investigate how host cell factors take part in integration of Human T-cell Leukemia virus and Rous sarcoma virus, building on structural studies of their intasomes, the protein–DNA complexes that insert viral DNA into chromosomes.
The school
University of California-San Diego: 84 labs on PI Pages, $1.9B a year on research, 637 research doctorates a year.
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