Projects and Grants
Projects funded by the National Institute of General Medical Sciences in the Krulwich Laboratory include:
Bacterial Strategies for Proton-Coupling and Managing Bioenergetic Workloads
Oxidative phosphorylation at high pH: a model system for probing the proton path during energization of ATP synthesis by the respiratory chain. Biochemical, molecular and biophysical studies of OXPHOS in mutant and wild-type cells, membranes and purified systems test the hypothesis of sequestered proton transfer during OXPHOS that depend upon special adaptations of the ATP synthase and respiratory chain complexes and may also depend upon specific membrane phospholipid content. In collaboration with Thomas Meier’s research group (Max Planck Biophysics Institute, Frankfurt, Germany), structural studies of the ATP synthase rotor are unraveling properties that relate to specific adaptations of the alkaliphile synthase as well as properties that are likely to be found more broadly among bacterial ATP synthases.
Mrp-type monovalent cation/proton antiporter systems: basis and roles for the unusual complexity of this major bacterial antiporter system. In collaboration with Masahiro Ito's lab (Toyo University, Japan), we study the catalytic properties, physiological roles and structural features of Mrp systems from bacteria such as pathogenic Staphylococcus aureus and non-pathogenic Bacillus species. We are testing the hypothesis that Mrp proteins form a complex that is a "consortium" of transporters that includes monovalent cation/proton antiporters and which function synergistically. We are also investigating a systems response by bacterial cells in which stresses that lead to an acute increase in Mrp function, thereby acutely reducing the membrane potential that energizes antiport, sets in motion a series of events that leads to a membrane potential that is even higher than in the absence of the original stress(es).
Structural Basis of Tetracycline Resistance by Efflux Pump TetL
Structure-function studies of the tetracycline efflux protein, TetL,that supports tetracycline-resistance in Gram-positive bacteria is being investigated with the goal of achieving information that will further define the catalytic capacities of the transporter and will inform design of inhibitors of the antibiotic-resistance protein. This funded as a sub-contract of a research grant whose PI is Da-Neng Wang (Skirball Institute, NYU) and the project is part of a collaboration with his research group.
Terry A. Krulwich, PhD
Annenberg Building Room 19-24
Pharmacology and Systems Therapeutics
1468 Madison Avenue
New York NY 10029