Implementing high-temperature short-time media treatment in commercial-scale cell culture manufacturing processes.

The production of therapeutic proteins by mammalian cell culture is complex and sets high requirements for process, facility, and equipment design, as well as rigorous regulatory and quality standards. One particular point of concern and significant risk to supply chain is the susceptibility to contamination such as bacteria, fungi, mycoplasma, and viruses. Several technologies have been developed to create barriers for these agents to enter the process, e.

Genome-wide inference of regulatory networks in Streptomyces coelicolor.

Background: The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses.

Mining manufacturing data for discovery of high productivity process characteristics.

Modern manufacturing facilities for bioproducts are highly automated with advanced process monitoring and data archiving systems. The time dynamics of hundreds of process parameters and outcome variables over a large number of production runs are archived in the data warehouse. This vast amount of data is a vital resource to comprehend the complex characteristics of bioprocesses and enhance production robustness.

Mining transcriptome data for function-trait relationship of hyper productivity of recombinant antibody.

In the past decade we have witnessed a drastic increase in the productivity of mammalian cell culture-based processes. High-producing cell lines that synthesize and secrete these therapeutics have contributed largely to the advances in process development. To elucidate the productivity trait in the context of physiological functions, the transcriptomes of several NS0 cell lines with a wide range of antibody productivity were compared.

Mining bioprocess data: opportunities and challenges.

Modern biotechnology production plants are equipped with sophisticated control, data logging and archiving systems. These data hold a wealth of information that might shed light on the cause of process outcome fluctuations, whether the outcome of concern is productivity or product quality. These data might also provide clues on means to further improve process outcome.

A bistable gene switch for antibiotic biosynthesis: the butyrolactone regulon in Streptomyces coelicolor.

Many microorganisms, including bacteria of the class Streptomycetes, produce various secondary metabolites including antibiotics to gain a competitive advantage in their natural habitat. The production of these compounds is highly coordinated in a population to expedite accumulation to an effective concentration. Furthermore, as antibiotics are often toxic even to their producers, a coordinated production allows microbes to first arm themselves with a defense mechanism to resist their own antibiotics before production commences.

Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2).

Background: A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. Overexpression of afsS in S. coelicolor and certain related species causes antibiotic stimulatory effects in the host organism.

In pursuit of a super producer-alternative paths to high producing recombinant mammalian cells.

Recombinant mammalian cells are used to produce numerous, high-value protein therapeutics. Generating hyper-producing cell lines is crucial for delivery of products to ailing patients. Better understanding of the complex trait of hyperproductivity can facilitate the creation of hyper-producing cell lines.

Transcriptome dynamics-based operon prediction and verification in Streptomyces coelicolor.

Streptomyces spp. produce a variety of valuable secondary metabolites, which are regulated in a spatio-temporal manner by a complex network of inter-connected gene products. Using a compilation of genome-scale temporal transcriptome data for the model organism, Streptomyces coelicolor, under different environmental and genetic perturbations, we have developed a supervised machine-learning method for operon prediction in this microorganism.

A framework to analyze multiple time series data: a case study with Streptomyces coelicolor.

Transcriptional regulation in differentiating microorganisms is highly dynamic involving multiple and interwinding circuits consisted of many regulatory genes. Elucidation of these networks may provide the key to harness the full capacity of many organisms that produce natural products. A powerful tool evolved in the past decade is global transcriptional study of mutants in which one or more key regulatory genes of interest have been deleted.

Permeability and reactivity of Thermotoga maritima in latex bimodal blend coatings at 80 degrees C: a model high temperature biocatalytic coating.

Thermostable polymers cast as thin, porous coatings or membranes may be useful for concentrating and stabilizing hyperthermophilic microorganisms as biocatalysts. Hydrogel matrices can be unstable above 65 degrees C. Therefore a 55-microm thick, two layer (cell coat + polymer top coat) bimodal, adhesive latex coating of partially coalesced polystyrene particles was investigated at 80 degrees C using Thermotoga maritima as a model hyperthermophile.