A functional enviromics method for cell culture media engineering

Abstract

This invention refers to a new method for optimizing the composition of cell culture media. This new method comprises two main stages. In the first stage, a functional enviromics map is built through the joint screening of cell functions and medium factors by the execution of a specific cell culture protocol and exometabolome assays protocol. The functional enviromics map consists of a data array of intensity values of elementary cellular functions against medium factors. In the second stage, optimized cell culture medium formulations are developed that either enhance or repress target elementary cellular functions from columns of the functional enviromics map. The main advantage of this method lies in enabling metabolic engineering through the culture media composition manipulation, wherein an arbitrarily high number of cell functions are optimized through manipulation of medium factors, as opposed to previous methods, which are eminently empirical, are not cell function oriented, and require a much higher number of experiments. Furthermore, this new method is based on cost-effective exometabolome assays and does not require costly intracellular genomic or proteomic assays.

Description

field of invention [0001] The present invention relates to methods for optimizing the composition of cell culture media. Methods are described for determining optimal values ​​of mediator factors to enhance or inhibit target essential cellular functions as desired by the user. The method comprises the construction of a functional environmental profile by performing cell culture experiments and preferably high-throughput analysis of the exometabolome, followed by mediator value adjustment based on said function of the mediator factor. Background of the invention [0002] Cell growth formulations contain hundreds of individual components in aqueous solutions. They generally consist of: nutrients such as peptones, amino acids, meat extracts and yeast extracts; minerals and vitamins, inhibitors and solidifying agents. Some of these components may be critical for cell growth or productivity, others may be toxic at some level, and many may participate in complex interactions wit...

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Problems solved by technology

However, such an approach presents 3 major problems: i) finding single molecular interactions has proven expensive and difficult, ii) there are well-known gaps between gene expression, proteome and cellular phenotype, iii) gene expression or the systematic collection of proteomic data is difficult and expensive

Although functional genomics is currently a very active field of research in cell biology, its complementary functional environmental omics has been mentioned in the context of mental health disorders [41] but in the context of cell biology Not previously mentioned nor used in cell culture media design

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