I-Corps: Software and Services to Enable Metabolic Flux Analysis

Vanderbilt University, Nashville TN

Investigators

Abstract

Metabolic flux analysis (MFA) allows for the determination of biochemical reaction rates inside of living cells, which are otherwise impossible to measure directly. Similar to how Google Maps reports traffic flows within highway networks, MFA can identify cellular pathway bottlenecks (roadblocks) and wasteful metabolic processes (detours) within biochemical networks. This information can be used to engineer improved production systems (e.g., host organisms and/or cultivation platforms) for use in industrial bioprocesses or agriculture. The MFA technology can also be used in biomedical research to identify potential therapeutic targets or diagnostic biomarkers for metabolic diseases. However, most companies do not have the necessary expertise to assess their measurements using MFA due to the sophisticated computational algorithms and data analysis required. At its simplest, the proposed project seeks to broaden the use of advanced metabolic engineering software and techniques developed in the PI?s laboratory for applications in the biotechnology and pharmaceutical industries. Metabolic flux analysis (MFA) is a complex analysis technique that encompasses molecular biology, chemistry, biochemistry, cell biology, plant physiology, mathematics, computer science, and engineering. The proposed approach to MFA will be rigorous because this team aims to capture as much information as possible from the available measurements that companies can obtain from their experimental system. Because of this, the immediate impacts within an organization will be an increase in the quality of the science performed. This I-Corps team aims to lead by example by creating testable hypotheses, validating its assumptions, accounting for all sources of error, and analyzing data with attention to detail. MFA, coupled with the proposed approach, has the potential to change for the better how companies perform metabolic engineering. Improved methodologies to assess cellular metabolism have the potential to drive tremendous advances in not just manufacturing efficiency, which is useful for everything from biofuels production to food production, but also for drug discovery and therapeutic applications in metabolic diseases such as cancer or diabetes.