Design of bioswitches for synthetic biology

Novel bioswitches are of great interest for synthetic biology, especially when dynamic control of metabolic fluxes is demanded. Among the natural bioswitches, riboswitches and allosteric proteins are of particular importance because of their wide distributions in nature. However, the application of natural bioswitches is often limited by their narrow response range and the engineering of allosteric proteins is challenging due to their dynamic feature and complex mechanisms, especially for non-natural ligands. In this presentation, first an efficient approach that is able to extend the ligand response range of riboswitches will be presented by taking advantage of the computer-aided rational design. A lysine riboswitch from E. coli I has been employed as a model system to demonstrate the procedure. Then, a novel strategy to explore and engineer ligand-induced allosteric regulation based on a new concept of thermodynamic model of protein conformational dynamics will be presented with the aim to create allosteric regulations for non-natural ligands. The key feature of the thermodynamic model is that the allosteric process upon ligand binding is divided into two sub-processes – conformational change and molecular binding. As a consequence, the ligand-induced allosteric regulation can be explored for each sub-process from both energetic and structural perspectives. To prove the concept, aspartokinase III from E. coli was used as a model system. Guided by the thermodynamic model, the natural ligand has been successfully altered from an inhibitor to an activator. Moreover, both inhibition and activation effects have been established for a non-natural ligand

Mitigating Greenhouse Gas Emissions from Winter Production of Agricultural Greenhouses

Consuming conventional fossil fuel, such as coal, natural gas, and oil, to heat agricultural greenhouses has contributed to the climate change and air pollutions regionally and globally, so the clean energy sources have been increasingly applied to replace fossil energies in heating agricultural greenhouses, especially in urban area. To assess the environment performance (e.g., greenhouse gas (GHG) emissions) of the ground source heat pump system (GSHPs) for heating agricultural greenhouses in urban area, a GSHPs using the shallow geothermal energy (SGE) in groundwater was applied to heat a Chinese solar greenhouse (G1) and a multispan greenhouse (G2) in Beijing (latitude 39°40′ N), the capital city of China. Emission rates of the GSHPs for heating the G1 and G2 were quantified to be 0.257–0.879 g CO2 eq. m−2 day−1. The total GHG emissions from heating greenhouses in Beijing with the GSHPs were quantified as 1.7–2.9 Gt CO2 eq. year−1 based on the electricity from the coal-fired power plant (CFPP) and the gas-fired power plant (GFPP). Among different stages of the SGE flow, the SGE promotion contributed most GHG emissions (66%) in total due to the higher consumption of electricity in compressors. The total GHG emissions from greenhouses heating with the coal-fired heating system (CFHs) and gas-fired heating system (GFHs) were quantified as 2.3–5.2 Gt CO2 eq. year−1 in Beijing. Heating the G1 and G2 with the GSHPs powered by the electricity from the CFPP, the equivalent CO2 emissions were 43% and 44% lower than directly burning coal with the CFHs but were 46% and 44% higher than the GFHs that burn natural gas. However, when using the GFPP-generated electricity to run the GSHPs, the equivalent CO2 emissions would be 84% and 47% lower than the CFHs and the GFHs, respectively

Increased transgene expression mediated by recombinant adeno-associated virus in human neuroglia cells under microgravity conditions

The space environment has the special characteristics of radiation, noise particularity and weightlessness, all of which have adverse effects on astronauts’ muscles, bones, neurons and immune system. Some reports have shown that chemotherapy and radiotherapy can increase the activity of the recombinant adeno-associated virus (AAV) which is widely used in gene therapy. In this paper, recombinant AAV2 (rAAV2) was first packaged with the enhanced green fluorescence protein (eGFP) gene and used to infect neuroglia cells including the U87 and U251 cell lines, under microgravity conditions; it was then detected by fluorescence microscopy and flow cytometry. The results show that microgravity affects the adhesion ability of cells, promotes transgene expression induced by rAAV2 and causes changes of viral infection receptors at different time points. These findings broaden the current understanding of the microgravity effects on rAAV, with significant implications in gene therapy and the mechanisms of increased virus pathogenicity under space microgravity.

B Cell Dysfunction Associated With Aging and Autoimmune Diseases

Impaired humoral responses, as well as an increased propensity for autoimmunity, play an important role in the development of immune system dysfunction associated with aging. Accumulation of a subset of atypical B cells, termed age-associated B cells (ABCs), is one of the key age-related changes in B cell compartments. ABCs are characterized by their distinct phenotypes, gene expression profiles, special survival requirements, variations in B cell receptor repertoires, and unique functions. Here, we summarize recent progress in the knowledge base related to the features of ABCs, their potential role in immune senescence, and their relationship with autoimmune diseases