Author(s)
Thomas E. Gorochowski
Published 9 Projects
Microscopy Bioinformatics Rna Seq Synthetic Biology Systems Biology
Content
Video Abstract (AI generated) (01:21) Paper Preprint Nature MethodsCells use feedback regulation to ensure robust growth despite fluctuating demands on resources and different environmental conditions. Yet the expression of foreign proteins from engineered constructs is an unnatural burden on resources that cells are not adapted for. Here we combined multiplex RNAseq with an in vivo assay to reveal the major transcriptional changes in two E. coli strains when a set of inducible synthetic constructs are expressed. We identified that native promoters related to the heat-shock response activate expression rapidly in response to synthetic expression, regardless of the construct. Using these promoters, we built a CRISPR/dCas9-based feedback regulation system that automatically adjusts synthetic construct expression in response to burden. Cells equipped with this general-use controller maintain capacity for native gene expression to ensure robust growth and as such outperform unregulated cells at protein yields in batch production. This engineered feedback is the first example of a universal, burden-based biomolecular control system and is modular, tuneable and portable.
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Thomas E. Gorochowski. (2021, Nov 3).Burden-driven feedback control of gene expression[Video]. Scitok. https://scitok.com/project/p/aeb80ca8
Ceroni F. "Burden-driven feedback control of gene expression" Scitok, uploaded by E. Gorochowski Thomas, 3 Nov, 2021, https://scitok.com/project/paeb80ca8
Thomas E. Gorochowski. "Burden-driven feedback control of gene expression" Scitok. (Nov 3, 2021). https://scitok.com/project/p/aeb80ca8
Thomas E. Gorochowski (Nov 3, 2021). Burden-driven feedback control of gene expression Scitok. https://scitok.com/project/p/aeb80ca8
Thomas E. Gorochowski. Burden-driven feedback control of gene expression[video]. 2021 Nov 3. https://scitok.com/project/p/aeb80ca8
@online{al2006link, title={ Burden-driven feedback control of gene expression }, author={ E. Gorochowski, Thomas }, organization={Scitok}, month={ Nov }, day={ 3 }, year={ 2021 }, url = {https://scitok.com/project/p/aeb80ca8}, }