Karl Schmitz
University of Delaware, DE·Biochemistry
Tuberculosis kills more people than any other bacterial infection, and drug-resistant strains are spreading. New antibiotic targets are needed.
- Fields
Biochemistry
Microbiology & Immunology
- Topics
tuberculosis
mycobacteria
antibiotic resistance
- Grants
- 1 known grant, through Jun 2029
What they work on
- Use phosphoproteomics to identify stress conditions that raise phosphoarginine (pArg) levels in mycobacteria, test whether pArg is needed for stress tolerance, and find the arginine kinases and phosphatases that add and remove it.
- Test in vitro, with purified proteins, how the number of pArg tags and the stability of the target protein affect degradation by the ClpC1P1P2 protease.
- Determine how pArg binding changes the activity state and assembly of ClpC1, the unfolding enzyme that feeds proteins to the protease.
- Assess how pArg-driven changes in ClpC2 oligomerization, its assembly into larger complexes, affect its role in sensing pArg and in antibiotic persistence.
More about the research
Promising candidates are the Clp proteases, molecular shredders that break down selected proteins inside Mycobacterium tuberculosis. These enzymes are essential for the bacteria's survival, yet scientists do not fully understand what they do or why they are needed. This project studies a chemical tag that may tell them which proteins to destroy: phosphoarginine (pArg), a phosphate group attached to the amino acid arginine.
Why it matters
Drug-resistant tuberculosis needs new antibiotics, and the Clp protease ClpC1 is a promising drug target. Detailed knowledge of how phosphoarginine tags direct protein breakdown could improve screens for new ClpC1-targeting drugs. Learning how the tags help bacteria survive stress and antibiotics may also guide future work on tuberculosis infection.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Klaas Van Wijk
Cornell University, NY·Plant Science & Agriculture
Determine which N-terminal amino acids act as degrons (destruction signals) in chloroplasts, using a new in vivo quantitative reporter system and testing the roles of the recognizer ClpS1 and the Clp chaperone-protease system.
Sabine Ehrt
Weill Medical College of Cornell University, NY·Microbiology & Immunology
Test whether mutations found repeatedly in patient strains in the metabolic enzymes PPGK, PEPCK and LDH change M. tuberculosis disease progression and antibiotic susceptibility, and identify the clinical pressures and interacting mutations that select them.
Katerina Darwin
New York University, NY·Microbiology & Immunology
Test whether host-derived aldehydes, reactive products of normal metabolism, act as immune effectors against Mycobacterium tuberculosis, using bacterial and mouse genetics plus biochemistry and cell biology.
The school
University of Delaware: 22 labs on PI Pages, $466M a year on research, 298 research doctorates a year.
Reach out
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