John R Jimah
Faculty AssistantMatt Montondo
- Ph.D. Biology and Biomedical Sciences, Washington University in St. Louis
- B.A. Molecular Biology, Colgate University
Research AreaBiochemistry, Biophysics & Structural Biology
Research FocusMembrane remodeling in human cells and parasites
Structural cell biology of malaria parasites
Malaria remains a serious global health problem with 200 million cases annually. There is growing drug resistance to current antimalarials and no effective vaccine. We study the structural cell biology of malaria and related parasites. Our primary structural methods are cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). We are particularly interested in membrane remodeling processes necessary for parasite propagation and human infection. Discovering the molecular mechanisms and structural basis of cellular processes in parasites will inform the development of new therapeutics to fight malaria.
Membrane remodeling in human cells
Membrane remodeling enables fundamental cellular processes including endocytosis (how cells take up nutrients and chemical messengers) and the maintenance of organelle architecture and biogenesis (organelles are regions of the cell with specialized functions, for example mitochondria). Mutations or dysregulation of the membrane remodeling machinery is associated with neuropathies, myopathies, and cancer. We investigate the mechanisms of membrane remodeling, particularly membrane fission, using multidisciplinary approaches from structural biology (cryo-EM/ET), biochemistry, biophysics, and cell biology.
Cryo-EM structures reveal multiple stages of bacterial outer membrane protein folding. Cell. 2022 ;185(7):1143-1156.e13. .
Synthesis and Effect of Conformationally Locked Carbocyclic Guanine Nucleotides on Dynamin. Biomolecules. 2022 ;12(4). .
The structure and spontaneous curvature of clathrin lattices at the plasma membrane. Dev Cell. 2021 ;56(8):1131-1146.e3. .
Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein. Nat Cell Biol. 2020 ;22(6):674-688. .
Structural Insights into the Mechanism of Dynamin Superfamily Proteins. Trends Cell Biol. 2019 ;29(3):257-273. .
Prediction of New Stabilizing Mutations Based on Mechanistic Insights from Markov State Models. ACS Cent Sci. 2017 ;3(12):1311-1321. .
Rhoptry Proteins ROP5 and ROP18 Are Major Murine Virulence Factors in Genetically Divergent South American Strains of Toxoplasma gondii. PLoS Genet. 2015 ;11(8):e1005434. .
Isoprenoid biosynthesis inhibition disrupts Rab5 localization and food vacuolar integrity in Plasmodium falciparum. Eukaryot Cell. 2013 ;12(2):215-23. .
John Jimah will start as an Assistant Professor of Molecular Biology at Princeton University in January 2022. His laboratory will investigate the molecular mechanism of membrane remodeling processes in human cells and malaria parasites primarily using structural biology (cryo-electron microscopy and tomography), cell biology, biochemical, and biophysical approaches. John grew up in Ghana and moved to the United States to attend college. He earned his B.A. in Molecular Biology from Colgate University. He received his Ph.D. in Biology and Biomedical Sciences from Washington University in St. Louis, in the lab of Dr. Niraj Tolia, as a fellow of the Chancellor’s Graduate Fellowship Program. There, he discovered the mechanism of the malaria vaccine candidate CelTOS in forming pores in human and mosquito cells to allow parasite traversal and propagation. Having developed an interest in membrane remodeling processes, he joined the laboratory of Dr. Jenny Hinshaw at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH. He was a Nancy Nossal fellow and member of the first class of NIGMS MOSAIC scholars. His postdoctoral studies focused on the membrane architecture of human cells and pathogens, elucidating the mechanisms of (1) dynamin-actin interaction during cell-cell fusion, (2) dynamin-mediated membrane fission during endocytosis, and (3) bacterial outer membrane protein folding.