Schibrowsky, Natalie
Natalie is in the Biochemistry, Molecular and Structural Biology Graduate Program, where she works in the laboratory of Dr. Jose Rodriguez. She received her Biochemistry B.S. in 2015 from the University of Nevada, Las Vegas, M.C.S. in Biological Chemistry at the University of Pennsylvania in 2017, and joined the CMB training program at UCLA in 2018.
Mentor: Dr. Jose Rodriguez
Nature self-assembles protein structures for various functions, including storage, protection, and fortification. These self-assemblies range from filaments to full three-dimensional crystals and are pervasive across the tree of life. They include the granules present in immune system cells, the packing of hormones in the pancreas, the storage of proteins in plants, carboxysomes, viruses, and cell-grown crystals in microbes. A better understanding of how certain organisms are able to naturally self-assemble macromolecules and how to recreate these in living cells must be achieved.
In order to determine if cell-grown crystals are affected by their pathways, structural studies must be conducted. My studies will focus on Bacillus thuringiensis (Bt), rod-shaped bacteria that, upon undergoing sporulation, produce cells containing an endospore (non-activated, dormant) and a toxin crystal. There have been recent successes of solving structures of cell-grown crystals, ie. Trypanosoma brucei cathepsin B grown in insect cells and the BinA/B subunits’ structures were all solved from cell-grown crystals by XFEL studies. With the recent developments in structure determination, I will utilize cryo-electron tomography (cryo-ET) to study this interaction and solve these complicated protein assemblies (like crystals) within the cell. By studying these structures, more information will be obtained about determining stabilized crystalline conditions and the metabolic and chemical environment that facilitates self-assembly. This study will focus on the development of cryo-ET with B. thuringiensis’ complexes and compare canonical crystallography and cryo-ET techniques to these conducted within cells. By understanding this system and technique, more downstream applications can be developed, such as the design of systems for controlled drug delivery and release, and macromolecular scaffolds.
