Anna Tischler
University of Minnesota, MN·Microbiology & Immunology
Tuberculosis kills and sickens more people each year than any other bacterial infection, and treatment takes months while drug-resistant strains spread. One route to better drugs is to shut down chemical pathways that the bacterium Mycobacterium tuberculosis needs to grow but that human cells do not have, so a drug would hit the microbe and spare the patient.
- Fields
Microbiology & Immunology
Biochemistry
Pharmacology
- Topics
Mycobacterium tuberculosis
drug resistance
antibiotic targets
- Grants
- 2 known grants, through Jun 2027
What they work on
- Build Mycobacterium tuberculosis strains whose phenylalanine-making enzymes can be switched on or off, and use them in macrophage and mouse infections to measure how much the bacterium needs this amino acid pathway during disease.
- Determine whether blocking phenylalanine synthesis makes M. tuberculosis more susceptible to existing anti-tuberculosis drugs, using the conditional-expression strains in infection models.
- Map the metabolic shifts and stress responses triggered by phenylalanine starvation in M. tuberculosis, combining transcriptomics of gene activity with metabolomics of internal small molecules.
- Use a strain with controllable expression of RibA2, the enzyme starting riboflavin synthesis, to test how vitamin starvation alters bacterial physiology and drug sensitivity, and build strains with reduced enzyme levels for future screening.
- Quantify how much M. tuberculosis depends on making its own riboflavin at different stages of infection, by tracking the RibA2 conditional strain in macrophages and mice.
- Identify the transporters that import riboflavin into M. tuberculosis using a synthetic lethal genetic screen, which finds gene disruptions that only become lethal when synthesis is also blocked.
More about the research
A gap in this strategy is that pathways essential in a laboratory flask may not be essential inside a host, where the bacterium might simply scavenge the nutrient from surrounding tissue. Two projects in this lab test that question for two different nutrients, and both ask whether blocking the pathway also makes existing tuberculosis antibiotics work better.
Why it matters
New tuberculosis drugs are needed to shorten the long treatment course and to fight multidrug-resistant strains. By testing whether the bacterium truly depends on making its own phenylalanine and riboflavin inside a host, this work could validate two drug targets that have no human counterpart, and the engineered bacterial strains it creates would give drug developers tools to search for inhibitors and for combinations that make current antibiotics more potent.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Christopher Brown
Weill Medical College of Cornell University, NY·Microbiology & Immunology·Early-career
Expose laboratory and clinical strains of Mycobacterium tuberculosis to air-drying stress and document the resulting changes in metabolism and cell envelope integrity.
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.
Sadiya Parveen-Nesson
Louisiana State University, LA·Microbiology & Immunology
Test whether blocking glutaminase (GLS1), the enzyme that breaks down glutamine, restores the TB-killing ability of Mtb-infected macrophages, using siRNA knockdown, chemical inhibition and macrophages from macrophage-specific GLS1 knockout mice.
The school
University of Minnesota: 88 labs on PI Pages, $1.4B a year on research, 722 research doctorates a year.
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