Microorganisms have been used for well over a century to experimentally unlock the mysteries metabolism and to better understand and control processes like fermentation. Much of what we know today about central metabolism was through simple, but ingenious, experimentation on yeast and bacteria. Much more recently, mammalian cells have been developed to treat diseases such as cancer. T-cells modified with chimeric antigen receptors (CAR-T), mesenchymal stem/stromal cells, and induced pluripotent stem cells (iPSC) all have potential for therapeutic applications. The challenge is to be able to reproducibly make cells for human use and to develop sets of markers called critical quality attributes (CQAs) that can be used to predict their function.
I believe that much can still be learned about metabolism and physiology from classical microorganisms using modern experimental techniques. Furthermore, many techniques and lessons learned from microorganisms can be successfully applied to cultured cells for human therapeutics. I will summarize our efforts to identify CQAs for cell therapeutics in the NSF Center for Manufacturing Technologies (CMaT) and also describe new experimental and computational approaches we have developed to study in vivo metabolism in Neurospora crassa.