Characterizing the Kinetics of Clinical Glucose-6-Phosphate Dehydrogenase Mutants
Denis Titov, Assistant Adjunct Professor
Nutritional Sciences and Toxicology
Closed. This professor is continuing with Spring 2026 apprentices on this project; no new apprentices needed for Fall 2026.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic defect across the globe, affecting over 400 million individuals. Formerly known as favism, the hallmark of this condition is the triggering of hemolytic anemia events upon exposure to certain environmental stressors including foods and medications. G6PD is the first enzyme of the pentose phosphate pathway (PPP), which is responsible for the generation of precursors for nucleotide synthesis and NADPH—an electron carrier metabolite—for reductive biosynthesis and antioxidant regeneration. While G6PD has been extensively studied in vitro, the mechanisms by which the enzyme is regulated, and by extension the mechanisms by which the PPP is regulated in the context of central carbon metabolism, have remained elusive and poorly understood. The Titov Lab pioneers biochemical and computational modeling approaches to study metabolic networks and their impact on human health and aging. The lab has developed a mathematical model for mammalian glycolysis that makes predictions on metabolite pool levels and reaction rates as they would occur in the cell in real time, and has recently extended the model to include the pentose phosphate pathway.
Role: The primary role of the undergraduate will be to perform in-vitro enzyme kinetic assays on G6PD variants to generate enzyme activity datasets. The student will also learn how to properly process and analyze data generated, which will be used for refining model predictions on the regulatory mechanisms of G6PD. The project will provide cross-disciplinary training at the intersection of molecular biology, metabolism, and computation biology. If interest and productivity persist throughout the semester, there will be opportunities to continue this project in future semesters. All contributions to the advancement of the project will be credited with inclusion as an author on future presentations and/or publications.
Qualifications: Undergraduates seeking to apply should be: (1) eager to learn (2) highly attentive to detail (3) highly motivated and organized (4) effective interpersonal communicators (5) open to asking questions and learning from mistakes. Previous research or computational experience is not required, although experience in biochemistry or molecular biology lab will be considered valuable. Hourly commitment will be discussed, but can be a minimum of 6 and maximum of 12 hours per week.
Day-to-day supervisor for this project: James Mbata, Graduate Student
Hours: to be negotiated
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Biological & Health Sciences