David Cafiso
University of Virginia, VA·Biophysics
Bacteria living in the gut or causing disease must scavenge scarce nutrients such as iron and vitamin B12. They do so with transporter proteins in their outer membrane.
- Fields
Biophysics
Biochemistry
Microbiology & Immunology
- Topics
membrane transport
TonB-dependent transporters
BtuB
- Grants
- 1 known grant, through Mar 2027
What they work on
- Test models of how TonB-dependent transporters such as BtuB, the vitamin B12 transporter, move nutrients across the E. coli outer membrane, using site-directed spin labeling and EPR spectroscopy on active proteins.
- Characterize transporter structural states seen only in living cells by running pulse EPR experiments, such as double electron-electron resonance (DEER) distance measurements, directly in intact E. coli.
- Examine how lipopolysaccharide, a major outer-membrane molecule, changes the structure of TonB-dependent transport proteins in the bacterial outer membrane.
- Use EPR in E. coli to map the protein-protein interactions that group outer-membrane proteins into islands and define the membrane's large-scale organization.
More about the research
In Escherichia coli (E. coli), these TonB-dependent transporters get their energy by coupling to TonB, a protein in the inner membrane. Examples include BtuB, which brings in vitamin B12, and FhuA, FecA and FepA, which bring in different forms of chelated iron (iron bound to carrying molecules). These transporters exist only in bacteria. They are abundant in Gram-negative species, important to the human microbiome, and essential to pathogens behind meningitis, cholera, pertussis and dysentery. That makes them possible targets for new antibiotics.
Why it matters
TonB-dependent transport exists only in bacteria and is essential for many pathogens, including those causing meningitis, cholera and pertussis. Understanding how these nutrient transporters work could help in developing new classes of antibiotics to treat bacterial infections. It could also clarify how gut bacteria acquire nutrients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dominik Konkolewicz
Miami University-Oxford, OH·Chemistry
Synthesize a new class of polymers using controlled polymerization to tune chain length, charge and hydrophobicity, and test which designs self-assemble with lipids into well-defined discs tens of nanometers across.
John Hunt
Columbia University, NY·Biophysics
Use single-molecule FRET with vitamin B12 quenching (smFRET-Q) to track individual substrate molecules in real time during ATP-driven transport by the E. coli importer BtuCD-F reconstituted into nanodiscs.
Michael Stephen Trent
University of Georgia, GA·Microbiology & Immunology
Develop an analytical tool that measures LPS molecules in transit, and combine it with mass spectrometry of the enzyme LpxC and LPS precursors to determine how the YejM-YciM system controls LPS production in E. coli.
The school
University of Virginia: 43 labs on PI Pages, $814M a year on research, 413 research doctorates a year.
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