Two members of the project group participated in this study, which reports on design, synthesis, and biological activities of a series of conformationally confined Lipid A mimetics based on β,α-trehalose-type scaffold. Synthetic tetraacylated bisphosphorylated Lipid A mimetics based on a β-GlcN(1↔1)α-GlcN scaffold selectively block the LPS binding site on both human and murine MD-2 and completely abolish lipopolysaccharide-induced pro-inflammatory signaling, thereby serving as antisepsis drug candidates. These findings suggest that besides the chemical structure, also the three-dimensional arrangement of the diglucosamine backbone of MD-2-bound Lipid A determines endotoxic effects on TLR4. Inhibitors of TLR4 signalling are also potent inhibitors of the first step (priming) in NLRP3 inflammasome activation, when TLR4 is involved (in case of G- bacterial infections).
COBISS.SI-ID: 3262344
To effectively fight against the acquired immunodeficiency syndrome epidemic, ongoing development of novel HIV protease inhibitors is required. We developed a high-throughput method for testing potential inhibitors of HIV protease that employs a ratiometric flow cytometry for analyzing large populations of cells that express the FRET-HIV sensor, which is based on a combination of a fluorescent protein pair, namely mCerulean and mCitrine. Similarly, a sensor for testing inflammasome activation by following caspase-1 activation could be developed.
COBISS.SI-ID: 5383706
Electronic computer circuits consisting of a large number of connected logic gates of the same type, such as NOR, can be easily fabricated and can implement any logic function. In contrast, designed genetic circuits must employ orthogonal information mediators owing to free diffusion within the cell. Combinatorial diversity and orthogonality can be provided by designable DNA- binding domains. Here, we employed the transcription activator–like repressors to optimize the construction of orthogonal functionally complete NOR gates to construct logic circuits. We used transient transfection to implement all 16 two-input logic functions from combinations of the same type of NOR gates within mammalian cells. Additionally, we present a genetic logic circuit where one input is used to select between an AND and OR function to process the data input using the same circuit. This demonstrates the potential of designable modular transcription factors for the construction of complex biological information-processing devices.
COBISS.SI-ID: 5408026