Generally speaking, my lab is interested in large multi-subunit complexes involved in human health. Our lab uses various biophysical techniques including cryo-electron microscopy as tools to study the function of these large macromolecular assemblies. Of particular interest are the atomic details of protein folding as carried out by chaperonins like hsp60/10 and the bacteriophage encoded phi-EL chaperonin. Efficient and correct protein folding is critical in preventing misfolded protein aggregation that can lead to loss of function and even disease. We study various human mitochondrial Hsp60 protein folding intermediates with a focus on the disease-causing point mutations, D29G and V98I, which may hopefully lead to treatment.A second project includes studies on the small heat shock protein hsp27. Charcot-Marie-Tooth disease and Distal Hereditary Motor Neuropathy cause dysfunction in nerves of the peripheral nervous system. Our studies aim to ease development of strategies for disease intervention through new effective drug therapies by determining the structure of Hsp27 in complex with its client proteins.A third project aims to elucidate the structural and functional roles of DapC, DapD, DapE, and DapF for future targeting with inhibitory compounds, using the advanced structural biology technique of cryo-electron microscopy to find the mechanism of interaction between the enzymes. Pathway enzymes will work in concert with each other through multi-subunit complex formation termed a metabolon. A metabolon is a transient multi-enzyme complex that mediates substrate channeling from one enzyme to the next. Metabolons increase efficiency and control of the metabolic flux by having enzymes interacting sequentially, passing the substrates and products directly to the active site of the next enzyme through a molecular tunnel or tether created by the multi-protein complex. We are reconstructing this metabolon from in-vitro recombinant proteins for structure determination using cryo-Electron Microscopy. In line with the overall aim of studying large multi-subunit complexes, the goal of this proposal is to obtain a mechanistic understanding of how proteins within the Dap pathway can be targets for antibiotic drugs. This research may provide information that can help in the development of novel interventions.A fourth project includes CAX-1, a plant vacuolar proton/calcium ion exchanger whose function is to maintain calcium homeostasis and to mediate responses to external stresses. It is expressed primarily in leaves where it contributes to tolerance of submergence, anoxic environments, and controls recovery production of reactive oxygen species. There is no structure of this plant membrane protein and so we are looking to get the structure either by X-ray crystallography or cryo-Electron Microscopy.Finally, with the overall aim of studying large multi-subunit complexes, the fifth and final project aims to obtain a mechanistic understanding of how protein translation is reprogrammed by RNA post-transcriptional modifications after a mosquito blood meal. This is a project in collaboration with Dr. Immo Hansen at NMSU where we have written an NIH ROI proposal together (I am co-PI). My contribution will be to determine the structure of the mosquito ribosome before and after a blood meal to determine complex composition to answer questions about ribosome regulation. This research may provide information that can help in the development of novel interventions resulting from knowledge about the biological regulation of mosquito reproduction, homeostasis, and mosquito-virus interactions.