Research

Our laboratory is focused on the elucidation of protein’s structure and function. To do so, lab members utilize various techniques available, ranging from Circular Dichroism to Macromolecular Crystallography.

The research in the lab is focused on two major topics: Magnetosome-related proteins, and effectors of the type III secretion system in pathogenic bacteria.

Background
Structural biology aims to understand the chemistry, interactions and basic biological functions governed by the three-dimensional structure of macromolecules. Knowledge of the three dimensional structure of a protein can provide enormous, basic, scientific insight into the function of that protein, facilitating elucidation of its biochemical function and its interactions with other proteins, RNA, DNA, or membranes in the cell. Similarly, protein-ligand interactions are crucial in many biological processes with implications for drug targeting, gene expression and biomineralization. X-ray crystallography is the most prolific technique for the structural analysis of proteins and protein complexes, and remains the ‘gold standard’ in terms of accuracy. Using X-ray crystallography, we can now realize to the high-resolution range, up to atomic or even electronic details, enabling a full coverage understanding of macromolecules and their interactions. Crystallography is the key methodology for macromolecule-ligand interaction research and structure-based biochemical studies.

Magnetosome related proteins
Magnetotactic bacteria are a phylogenetically and morphologically diverse group of microorganisms that share an ability to create magnetosomes: biomineral organelles that sense geomagnetic fields and aid the bacteria to align themselves accordingly. The magnetosome organelle comprises aligned 30-50 nm iron oxide magnetite crystals, surrounded by a lipid bilayer membrane vesicle. There are several types of magnetosome-forming proteins all encoded by genes within a genomic island common to magnetotactic bacteria. These proteins include a set of incorporated membrane proteins that facilitate vesicle formation, vesicle localization and iron transport, and a set of proteins that control magnetite formation and size. A large number of the proteins involved in magnetosome formation are of unknown function. Magnetite crystals formed by magnetotactic bacteria have a high potential for nano- and biotechnological applications, which require specifically-designed particle surfaces of distinct shape and size. Using a biomimetic approach, we can use the purified proteins, possibly mutated, to design and control the magnetite crystals, for many uses including protein tags and fluorophores. For commercial use, magnetite crystals with a permanent, stable, magnetic dipole moment at room temperature and with a specific size can be designed.

Effectors of the Type III secretion system in pathogenic bacteria
The Type III secretion system is one of the most common pathways by which pathogenic bacteria secrete toxins for their survival and proliferation. Various, and notorious, Gram-negative bacteria utilize this system: Enterophatogenic and Enterohemorrhagic E. Coli (EPEC/EHEC), Yersinia pestis, Salmonella typhimurium, etc. The system is comprised of an injectisome apparatus, which functions as a physical bridge that enables the shuttling of effectors/toxic proteins into the host cell cytoplasm. These effectors utilize their highly evolved structural mimicry to subvert key activities or functions of the host cell for the advantage of the bacteria’s life cycle. Due to the nature of these effector’s structural mimicry, at the lab we aim at elucidating the structure/function relationship of these effectors, as well as identifying their targeted protein within the host’s cell.

The laboratory is also involved in performing structural and functional collaborations with various labs both in BGU and around the world to promote structural understanding.