Alejandro P. Heuck, assistant professor of Biochemistry and Molecular Biology, has received a five-year, $950,000 grant from the National Institutes of Health’s National Institute of General Medicine for his project “Molecular Mechanism of Translocon Assembly into Cell Plasma Membranes.”
The goal of this project is to analyze the structure and mechanism of assembly of the type III secretion translocon complex employed by pathogenic bacteria to inject virulence factors through the plasma membrane of human cells.
Employing a combination of biochemical and biophysical techniques the Heuck’s research group aims to unambiguously address fundamental structural aspects of the T3S translocon structure and assembly. By selective incorporation of various probes in the P. aeruginosa translocators, they will study which segments of the translocon proteins are essential to determine the characteristics of the transmembrane channel, what segments form the contact interface between the needle and the translocon, and how the translocators are arranged in the translocon complex formed in the mammalian cell membrane.
In addition to elucidate fundamental aspects of translocon assembly into lipid bilayers, these studies may ultimately lead to novel therapeutic strategies that block protein translocation and interfere with bacterial colonization in a broad variety of threatening human pathogens. Pathogens like Pseudomonas aeruginosa, the major cause of death in cystic fibrosis patients, are particularly problematic not only because of their ubiquitous nature but also because of their resistance to most antibiotics.