Christopher Radka
University of Kentucky, KY·Microbiology & Immunology·Early-career
Bacteria that live in and on the human body, both harmless residents and dangerous pathogens, can chemically alter fats they find in host tissue, and some of these altered fats quiet inflammation. The enzyme at the center of this work is oleate hydratase (OhyA).
- Fields
Microbiology & Immunology
Biochemistry
Biophysics
- Topics
oleate hydratase
OhyA
hydroxy fatty acids
- Grants
- 2 known grants, through Jul 2030
What they work on
- Determine how oleate hydratase (OhyA), a bacterial enzyme, extracts unsaturated fatty acid substrates from cell membranes, using crystal structures of OhyA bound to liposomes and mapping of its membrane-targeting domains.
- Compare OhyA–membrane interactions across bacterial taxa to define the molecular rules of how this enzyme docks onto and modifies lipid bilayers.
- Test how bacteria use OhyA and distribute hydroxy fatty acids to support gut colonization and shape immune responses, using diverse mouse models of the intestinal microbiome and mass-spectrometry lipidomics.
- Elucidate how unusual OhyA variants that lack the typical functional domains still catalyze fatty acid hydration, with implications for enzyme engineering.
- Test whether hydroxy fatty acids suppress innate immunity by blocking pathogen-associated molecular patterns from binding immune receptors, by loading onto lipid-presenting CD1 molecules to dampen T cell activation, or by signaling through G-protein coupled receptors and PPAR alpha.
- Test whether Staphylococcus aureus packages OhyA into extracellular vesicles that deliver hydroxy fatty acid mediators to surrounding host tissue, and define how OhyA binding alters membrane structure to promote vesicle formation.
More about the research
It takes unsaturated fatty acids, fats carrying a carbon–carbon double bond that are abundant at host surfaces, and adds water across that bond to make hydroxy fatty acids (hFAs). Bacteria carrying OhyA do not make unsaturated fatty acids themselves, so they meet these substrates only at the interface with host tissue. Two projects ask how this enzyme reaches fats inside a membrane, and how the hFAs it makes change the immune response.
Why it matters
Understanding how bacteria convert host fats into anti-inflammatory signals could point to new ways to treat infection and inflammation. Because oleate hydratase has no human counterpart and is needed for Staphylococcus aureus to establish infection in mice, it may be a target for antibacterial drugs. The same chemistry could inform microbiome-based approaches to intestinal inflammation and metabolic disorders, and the enzymes themselves could be engineered as biocatalysts.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Pagliarini
Washington University in St Louis, MO·Biochemistry
Determine the chemical reactions catalyzed by ACAD10 and ACAD11, two enzymes that prepare 4-hydroxy fatty acids for fat burning, and test whether their kinase domain adds a phosphate group at the 4-hydroxy position, using enzymology and structural biology.
Fata Moradali
University of Louisville, KY·Microbiology & Immunology
Compare the chemical structure of lipopolysaccharide from wild-type P. gingivalis strain 381 with that from mutants lacking the c-di-AMP-degrading enzyme pdepg or the regulator cdaR, using large-scale purification, chromatographic fractionation, FLATn, MALDI-ToF mass spectrometry, and NMR.
Madison Collins
Montana State University, MT·Microbiology & Immunology
Test the hypothesis that molecules controlled by the S. aureus SaeR/S gene regulatory system disrupt autophagy, a self-digestion process that kills trapped microbes, in human neutrophils after they swallow the bacteria.
The school
University of Kentucky: 34 labs on PI Pages, $528M a year on research, 319 research doctorates a year.
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