Bisharyan Y.,Cornell University |
Bisharyan Y.,Tetragenetics |
Clark T.G.,Cornell University
Mitochondrion | Year: 2011
Here we demonstrate that ciliated protozoa can jettison mitochondria as intact organelles, releasing their contents to the extracellular space either in a soluble form, or in association with membrane vesicles at the cell periphery. The response is triggered by lateral clustering of GPI-anchored surface antigens, or by heat shock. In the first instance, extrusion is accompanied by elevated levels of intracellular calcium and is inhibited by Verapamil and BAPTA-AM arguing strongly for the involvement of calcium in triggering the response. Cells survive mitochondrial discharge raising the interesting possibility that extrusion is an early evolutionary adaptation to cell stress. © 2011 Elsevier B.V. and Mitochondria Research Society. Source
Tetragenetics | Date: 2012-05-29
This invention is directed to methods for the production of immunogenic granular particles. In certain embodiments, the invention is directed to methods and products for the production immunogenic granular particles produced in ciliates. In certain embodiments, the invention is directed to compositions comprising Grl/Ag fusion polypeptides.
Agency: Department of Defense | Branch: Army | Program: STTR | Phase: Phase II | Award Amount: 750.00K | Year: 2007
Recombinant proteins are critically important in a wide range of applications that extend from the treatment of human and animal disease, to chemical and biological defense. Production of genetically engineered vaccine antigens, therapeutic proteins (including monoclonal antibodies), industrial enzymes, biopolymers, and bioremediation agents now constitutes a multibillion dollar-per-year industry. However, the need for low cost systems for the rapid production of these proteins remains great. In Phase I we demonstrated feasibility of the use of a free-living ciliate, Tetrahymena thermophila, as novel platform for high-level expression of the H5 hemagglutinin of avian influenza virus. In Phase II we will extend this work to commercially relevant enzymes, and antibody fragments targeted against biowarfare agents with the goal of benchmarking both yield and production costs against competing systems. In addition, we will develop user-friendly protein expression kits for the research tool market based on the TetraExpressTM platform.
Tetragenetics | Date: 2014-03-04
This invention is directed to methods for recombinant polypeptide production and, in particular, methods and products for the production of recombinant polypeptides in ciliates.
Madinger C.L.,New England Biolabs |
Collins K.,University of California at Berkeley |
Collins K.,Tetragenetics |
Fields L.G.,New England Biolabs |
And 2 more authors.
Eukaryotic Cell | Year: 2010
The growth, survival, and life cycle progression of the freshwater ciliated protozoan Tetrahymena thermophila are responsive to protein signals thought to be released by constitutive secretion. In addition to providing insights about ciliate communication, studies of constitutive secretion are of interest for evaluating the utility of T. thermophila as a platform for the expression of secreted protein therapeutics. For these reasons, we undertook an unbiased investigation of T. thermophila secreted proteins using wild-type and secretion mutant strains. Extensive tandem mass spectrometry analyses of secretome samples were performed. We identified a total of 207 secretome proteins, most of which were not detected in a set of abundant whole-cell protein identifications. Numerous proteases and other hydrolases were secreted from cells grown in rich medium but not cells transferred to a nutrient starvation condition. On the other hand, we detected the starvation-enhanced secretion of a small number of cytosolic proteins, suggestive of an exosome-like pathway in T. thermophila. Subsets of proteins from the T. thermophila regulated secretion pathway were detected with differential representation across strains and culture conditions. Finally, many secretome proteins had a predicted N-terminal signal sequence but no other annotated characteristic or functional classification. Our work provides the first comprehensive analysis of secreted proteins in T. thermophila and establishes the groundwork for future studies of constitutive protein secretion biology and biotechnology in ciliates. © 2010, American Society for Microbiology. Source