Project description:Analysis of the contribution of the post-transcriptional regulator CsrA to translation during exponential growth in Escherichia coli
Project description:Analysis of the contribution of the post-transcriptional regulator CsrA to translation during exponential growth in Escherichia coli
Project description:Analysis of RNA binding partners of the post-transcriptional regulator CsrA to translation during exponential growth in Escherichia coli
Project description:The fitness landscape is a concept commonly used to describe evolution towards optimal phenotypes. It can be reduced to mechanistic detail using genome-scale models (GEMs) from systems biology. We use recently developed GEMs of Metabolism and protein Expression (ME-models) to study the distribution of Escherichia coli phenotypes on the rate-yield plane. We found that the measured phenotypes distribute non-uniformly to form a highly stratified fitness landscape. Systems analysis of ME-model simulations suggest that this stratification results from discrete ATP generation strategies. Accordingly, we define "aero-types", a phenotypic trait that characterizes how a balanced proteome can achieve a given growth rate by modulating 1) the relative utilization of oxidative phosphorylation, glycolysis, and fermentation pathways; and 2) the differential employment of electron-transport-chain enzymes. This global, quantitative, and mechanistic systems biology interpretation of fitness landscape formed upon proteome allocation offers a fundamental understanding of bacterial physiology and evolution dynamics.
Project description:Small RNAs recently emerged as a new class of mobile instructive signals in development. Here, we investigate their mechanism of action and show that the gradients formed by mobile small RNAs generate sharply defined domains of target gene expression. By modulating the source of artificial miRNAs we show that boundary formation is an inherent property of the small RNA gradient itself. The threshold-based readout of such gradients is highly sensitive to small RNA levels at the source, allowing plasticity in the positioning of a target gene expression boundary. In addition to generating sharp expression domains of their immediate targets, the readouts of opposing small RNA gradients enable formation of stable and uniformly positioned developmental boundaries. These novel patterning properties of small RNAs are reminiscent of those of morphogens in animal systems. However, their exceptionally high specificity, direct mode of action, and the fully intrinsic nature of their gradients, distinguish mobile small RNAs from classical morphogens. Our findings present mobile small RNAs and their targets as highly portable and evolutionarily-tractable regulatory modules through which to create pattern in development and beyond.
Project description:Investigation of whole genome gene expression level changes in a Escherichia coli MG1655 K-12 ?fnr mutant, compared to the wild-type strain. The mutations engineered into this strain produce a strain lacking the FNR protein. WT strains were grown under aerobic and anaerobic growth conditions.
Project description:Investigation of whole genome gene expression level changes in a Escherichia coli MG1655 K-12 ?fnr mutant, compared to the wild-type strain. The mutations engineered into this strain produce a strain lacking the FNR protein. WT strains were grown under aerobic and anaerobic growth conditions. A six chip study using total RNA recovered from two separate cultures of Escherichia coli MG1655 K-12 WT (aerobic and anaerobic) and two separate cultures of the ?fnr mutant strain (anaerobic). Each chip measures the expression level of 4,661 genes from Escherichia coli MG1655 K-12 with eight 60-mer probes per gene, with each probe represented twice on the array.
Project description:5-aminovalerate (5AVA), L-lysine derived compound, represents a potential building block for the production of the bio-plastic nylon-5. Escherichia coli has been engineered for the production of 5AVA, but Corynebacterium glutamicum has never been engineered for the production of 5AVA, but, a lot of work was done in the last decades to optimize the production of the precursor L-lysine and more recently cadaverine. 5AVA added to the growth medium hardly affected growth rate of C. glutamicum, since, a half-inhibitory concentration of 1.1 M 5AVA was determined. While in E. coli, 5AVA production was engineered by using the DavBA pathway from Pseudomonas putida, here a pathway based on the route described in P. aeruginosa was established. C. glutamicum wild type was converted into a 5AVA producing strain by heterologous expression of L-lysine decarboxylase (LdcC), putrescine transaminase (PatA) and γ-aminobutyraldehyde dehydrogenase (PatD) genes from E. coli. 5AVA production was improved by using a strain previously engineered for high L-lysine production, by de-repressing phosphoenolpyruvate phosphotransferase system (PTS) and glycolysis and by avoiding formation of the by-product L-lactate. 5AVA accumulation by this strain was increased to 44.9 mM, representing a yield of 202 mmol mol-1 glucose, which is about three times higher than the highest yield achieved in E. coli for the production of 5AVA from glucose fermentation.
Project description:hPSC-CM has been used to model cardiac-related disease phenotypes. However, hPSC-CMs constrains their potential in cell-based therapy, disease modeling and drug discovery. Engineered heart tissues (EHT) or scaffold generated structures are unable to recapitulate the cardiovascular systems sufficiently to improve clinical reliance. Hence in this study, we demonstrate the
