Michael D Lynch

Research Themes

Computational Modeling of Biological Systems, Drug & Gene Delivery, Synthetic & Systems Biology

Research Interests

Focused on genetically engineering microbes to shut off their growth circuits and turn on new pathways to produce different compounds—improving production of biofuels, pharmacological molecules and industrial chemicals.

Education

• Ph.D. University of Colorado, Boulder, 2005
• M.D. University of Colorado, School of Medicine, 2007

Positions

• W. H. Gardner, Jr. Associate Professor of Biomedical Engineering
• Associate Professor in the Department of Biomedical Engineering
• Associate Professor in Chemistry
• Associate of the Duke Initiative for Science & Society

Courses Taught

• EGR 393: Research Projects in Engineering
• BME 792: Continuation of Graduate Independent Study
• BME 791: Graduate Independent Study
• BME 790L: Advanced Topics with the Lab for Graduate Students in Biomedical Engineering
• BME 590L: Special Topics with Lab
• BME 493: Projects in Biomedical Engineering (GE)

Publications

• Hennigan JN, Menacho-Melgar R, Sarkar P, Golovsky M, Lynch MD. Scalable, robust, high-throughput expression & purification of nanobodies enabled by 2-stage dynamic control. Metabolic engineering. 2024 Sep;85:116–30.
• Li S, Ye Z, Moreb EA, Menacho-Melgar R, Golovsky M, Lynch MD. 2-Stage microfermentations. Metabolic engineering communications. 2024 Jun;18:e00233.
• Decker JS, Yano U, Melgar RM, Lynch MD. Phase separation methods for protein purification: A meta-analysis of purification performance and cost-effectiveness. Biotechnology journal. 2024 Apr;19(4):e2400005.
• Decker J, Yano U, Melgar RM, Lynch M. Precipitation and Extraction Methods for Protein Purification: A Meta-Analysis of Purification Performance and Cost-Effectiveness. bioRxiv. 2023.
• Hennigan J, Menacho-Melgar R, Sarkar P, Lynch M. Scalable, Robust, High-throughput Expression, Purification & Characterization of Nanobodies Enabled by 2-Stage Dynamic Control. bioRxiv. 2023.
• Yang T, Ye Z, Lynch MD. "Multiagent" Screening Improves Directed Enzyme Evolution by Identifying Epistatic Mutations. ACS synthetic biology. 2022 May;11(5):1971–83.
• Decker JS, Menacho-Melgar R, Lynch MD. Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate. Biochemical engineering journal. 2022 Apr;181:108403.
• Moreb EA, Lynch MD. A Meta-Analysis of gRNA Library Screens Enables an Improved Understanding of the Impact of gRNA Folding and Structural Stability on CRISPR-Cas9 Activity. The CRISPR journal. 2022 Feb;5(1):146–54.
• Decker JS, Menacho-Melgar R, Lynch MD. Integrated Autolysis, DNA Hydrolysis and Precipitation Enables an Improved Bioprocess for Q-Griffithsin, a Broad-Spectrum Antiviral and Clinical-Stage anti-COVID-19 Candidate. bioRxiv. 2022 Jan 3;
• Li S, Ye Z, Moreb E, Menacho-Melgar R, Lynch M. The Development of 2-stage Microfermentation Protocols for High Throughput Cell Factory Evaluations. bioRxiv. 2022.
• Menacho-Melgar R, Lynch MD. Simple Scalable Protein Expression and Extraction Using Two-stage Autoinducible Cell Autolysis and DNA/RNA Autohydrolysis in Escherichia coli. Bio-protocol. 2022 Jan;12(2):e4297.
• Hennigan JN, Lynch MD. The past, present, and future of enzyme-based therapies. Drug discovery today. 2022 Jan;27(1):117–33.
• Menacho-Melgar R, Lynch MD. Measuring Oligonucleotide Hydrolysis in Cellular Lysates via Viscosity Measurements. Bio-protocol. 2022 Jan;12(2):e4304.
• Menacho-Melgar R, Hennigan JN, Lynch MD. Optimization of phosphate-limited autoinduction broth for two-stage heterologous protein expression in Escherichia coli. BioTechniques. 2021 Nov;71(5):566–72.
• Ye Z, Li S, Hennigan JN, Lebeau J, Moreb EA, Wolf J, et al. Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli. Metabolic engineering. 2021 Nov;68:106–18.
• Moreb EA, Lynch MD. Genome dependent Cas9/gRNA search time underlies sequence dependent gRNA activity. Nature communications. 2021 Aug;12(1):5034.
• Rios J, Lebeau J, Yang T, Li S, Lynch MD. A critical review on the progress and challenges to a more sustainable, cost competitive synthesis of adipic acid. Green Chemistry. 2021 May 7;23(9):3172–90.
• Lynch MD. The bioprocess TEA calculator: An online technoeconomic analysis tool to evaluate the commercial competitiveness of potential bioprocesses. Metabolic engineering. 2021 May;65:42–51.
• Efromson JP, Li S, Lynch MD. BioSamplr: An open source, low cost automated sampling system for bioreactors. HardwareX. 2021 Apr;9:e00177.
• Li S, Ye Z, Moreb EA, Hennigan JN, Castellanos DB, Yang T, et al. Dynamic control over feedback regulatory mechanisms improves NADPH flux and xylitol biosynthesis in engineered E. coli. Metabolic engineering. 2021 Mar;64:26–40.
• Moreb EA, Lynch M. A meta-analysis of gRNA library screens enables an improved understanding of the impact of gRNA folding and structural stability on CRISPR-Cas9 activity. 2021;
• Yang T, Ye Z, Lynch M. “Multi-Agent” Screening Improves the Efficiency of Directed Enzyme Evolution. 2021;
• Menacho-Melgar R, Yang T, Lynch M. Instant Taq: Rapid Autoinducible Expression and Chromatography-free Purification of Taq polymerase. 2021;
• Moreb EA, Lynch MD. An Analysis of gRNA Sequence Dependent Cleavage Highlights the Importance of Genomic Context on CRISPR-Cas Activity. 2021;
• Menacho-Melgar R, Hennigan J, Lynch M. Optimization of Phosphate Limited Autoinduction Broth for 2-Stage Heterologous Protein Expression in E. coli. 2021;
• Ye Z, Moreb EA, Li S, Lebeau J, Menacho-Melgar R, Munson M, et al. Escherichia coli Cas1/2 Endonuclease Complex Modifies Self-Targeting CRISPR/Cascade Spacers Reducing Silencing Guide Stability. ACS synthetic biology. 2021 Jan;10(1):29–37.
• Moreb EA, Hutmacher M, Lynch MD. CRISPR-Cas "Non-Target" Sites Inhibit On-Target Cutting Rates. The CRISPR journal. 2020 Dec;3(6):550–61.
• Menacho-Melgar R, Ye Z, Moreb EA, Yang T, Efromson JP, Decker JS, et al. Scalable, two-stage, autoinduction of recombinant protein expression in E. coli utilizing phosphate depletion. Biotechnology and bioengineering. 2020 Sep;117(9):2715–27.
• Menacho-Melgar R, Moreb EA, Efromson JP, Yang T, Hennigan JN, Wang R, et al. Improved two-stage protein expression and purification via autoinduction of both autolysis and auto DNA/RNA hydrolysis conferred by phage lysozyme and DNA/RNA endonuclease. Biotechnology and bioengineering. 2020 Sep;117(9):2852–60.
• Moreb EA, Ye Z, Efromson JP, Hennigan JN, Menacho-Melgar R, Lynch MD. Media Robustness and Scalability of Phosphate Regulated Promoters Useful for Two-Stage Autoinduction in E. coli. ACS synthetic biology. 2020 Jun;9(6):1483–6.
• Li S, Moreb E, Ye Z, Hennigan J, Castellanos DB, Yang T, et al. Dynamic control over feedback regulatory mechanisms improves NADPH fluxes and xylitol biosynthesis in engineeredE. coli. 2020;
• Moreb E, Ye Z, Efromson J, Hennigan J, Menacho-Melgar R, Lynch M. Robustness testing and scalability of phosphate regulated promoters useful for two-stage autoinduction inE. coli. 2020;
• Efromson J, Li S, Lynch M. BioSamplr: An open source, low cost automated sampling system for bioreactors. 2020;
• Li S, Ye Z, Lebeau J, Moreb E, Lynch M. Dynamic control over feedback regulation identifies pyruvate-ferredoxin oxidoreductase as a central metabolic enzyme in stationary phaseE. coli. 2020;
• Hennigan J, Wagner P, Burk C, Efromson J, Ye Z, Lipscomb M, et al. A Technoeconomic Evaluation of the Potential of Industrial Biotechnology for the Competitive Production of Commodity and Bulk Chemicals. 2020;
• Decker JS, Menacho-Melgar R, Lynch MD. Low-Cost, Large-Scale Production of the Anti-viral Lectin Griffithsin. Frontiers in bioengineering and biotechnology. 2020 Jan;8:1020.
• Ye Z, Lebeau J, Moreb E, Menacho-Melgar R, Lynch M. TheE. coliCas1/2 endonuclease complex reduces CRISPR/Cascade guide array stability. 2020;
• Lebeau J, Efromson JP, Lynch MD. A Review of the Biotechnological Production of Methacrylic Acid. Frontiers in bioengineering and biotechnology. 2020 Jan;8:207.
• Ye Z, Li S, Hennigan J, Lebeau J, Moreb E, Wolf J, et al. Two-stage Dynamic Deregulation of Metabolism Improves Process Robustness & Scalability in EngineeredE. coli. 2020;
• Menacho-Melgar R, Decker JS, Hennigan JN, Lynch MD. A review of lipidation in the development of advanced protein and peptide therapeutics. Journal of controlled release : official journal of the Controlled Release Society. 2019 Feb;295:1–12.
• Menacho-Melgar R, Ye Z, Moreb E, Yang T, Efromson J, Decker J, et al. Improved, scalable, two-stage, autoinduction of recombinant protein expression in E. coli utilizing phosphate depletion. 2019;
• Moreb EA, Hoover B, Yaseen A, Valyasevi N, Roecker Z, Menacho-Melgar R, et al. Managing the SOS Response for Enhanced CRISPR-Cas-Based Recombineering in E. coli through Transient Inhibition of Host RecA Activity. ACS synthetic biology. 2017 Dec;6(12):2209–18.
• Burg JM, Cooper CB, Ye Z, Reed BR, Moreb EA, Lynch MD. Large-scale bioprocess competitiveness: the potential of dynamic metabolic control in two-stage fermentations. Current Opinion in Chemical Engineering. 2016 Nov 1;14:121–36.
• Lynch MD. Into new territory: improved microbial synthesis through engineering of the essential metabolic network. Current opinion in biotechnology. 2016 Apr;38:106–11.
• Lynch MD. A rational microbial design perspective in the design build test era. In: Metabolic Engineering X. 2014. p. 505–28.
• Garst A, Lynch M, Evans R, Gill RT. Strategies for the multiplex mapping of genes to traits. Microbial cell factories. 2013 Oct;12:99.
• Boyle NR, Reynolds TS, Evans R, Lynch M, Gill RT. Recombineering to homogeneity: extension of multiplex recombineering to large-scale genome editing. Biotechnology journal. 2013 May;8(5):515–22.
• Lipscomb TW, Lipscomb ML, Gill RT, Lynch MD. Metabolic Engineering of Recombinant E. coli for the Production of 3-Hydroxypropionate. In: Engineering Complex Phenotypes in Industrial Strains. 2012. p. 185–120.
• Warnecke TE, Lynch MD, Lipscomb ML, Gill RT. Identification of a 21 amino acid peptide conferring 3-hydroxypropionic acid stress-tolerance to Escherichia coli. Biotechnology and bioengineering. 2012 May;109(5):1347–52.
• Lipscomb ML, Lipscomb TW, Liao H, Maness P, Lynch MD. Production of fungible diesel via fatty acid synthesis from hydrogen and carbon dioxide feedstocks. In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. AMER CHEMICAL SOC; 2012.
• Watson FD, Mercogliano CP, Ribble WK, Anderson RD, Liao HH, Lipscomb TW, et al. Enzyme engineering of malonyl coA reductase (MCR) to improve 3-hydroxypropionate (3HP) production. In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. AMER CHEMICAL SOC; 2012.
• Lynch MD, Manness PC, Lipscomb M, Warnecke T, Liao H. Novel biological conversion of hydrogen and carbon dioxide directly into biodiesel. In: ACS National Meeting Book of Abstracts. 2011.
• Lipscomb ML, Warnecke T, Hans L, Maness LP, Lynch MD. Novel biological conversion of hydrogen and carbon dioxide directly into biodiesel. In: ACS National Meeting Book of Abstracts. 2011.
• Mercogliano CP, Liao HH, Lynch MD. Enzyme evolution of an alpha-keto decarboxylase. In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. AMER CHEMICAL SOC; 2011.
• Prior JE, Lynch MD, Gill RT. Broad-host-range vectors for protein expression across gram negative hosts. Biotechnology and bioengineering. 2010 Jun;106(2):326–32.
• Warnecke TE, Lynch MD, Karimpour-Fard A, Lipscomb ML, Handke P, Mills T, et al. Rapid dissection of a complex phenotype through genomic-scale mapping of fitness altering genes. Metabolic engineering. 2010 May;12(3):241–50.
• Singh A, Lynch MD, Gill RT. Genes restoring redox balance in fermentation-deficient E. coli NZN111. Metabolic engineering. 2009 Nov;11(6):347–54.
• Gall S, Lynch MD, Sandoval NR, Gill RT. Parallel mapping of genotypes to phenotypes contributing to overall biological fitness. Metabolic engineering. 2008 Nov;10(6):382–93.
• Warnecke TE, Lynch MD, Karimpour-Fard A, Sandoval N, Gill RT. A genomics approach to improve the analysis and design of strain selections. Metabolic engineering. 2008 May;10(3–4):154–65.
• Bonomo J, Lynch MD, Warnecke T, Price JV, Gill RT. Genome-scale analysis of anti-metabolite directed strain engineering. Metabolic engineering. 2008 Mar;10(2):109–20.
• Lynch MD, Warnecke T, Gill RT. SCALEs: multiscale analysis of library enrichment. Nature methods. 2007 Jan;4(1):87–93.
• Lynch MD, Gill RT. Broad host range vectors for stable genomic library construction. Biotechnology and bioengineering. 2006 May;94(1):151–8.
• Lynch MD, Warnecke T, Singh A, Gill RT. Genomics tools for elucidating the function of trait conferring genes. In: AIChE Annual Meeting, Conference Proceedings. 2005. p. 9189.
• Warnecke T, Lynch MD, Gill RT. Identification of organic acid tolerance genes in E. coli for biorefinery applications. In: AIChE Annual Meeting, Conference Proceedings. 2005. p. 8984.
• Warnecke TE, Lynch MD, Gill RT. Post-genomics approach to understanding E. Coli network architecture. In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. AMER CHEMICAL SOC; 2005. p. U227–U227.
• Lynch MD, Warnecke T, Gill RT. Mixed-library parallel gene trait mapping: A quantitative micro-array technique for the genome-wide identification of trait conferring genes. In: ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. AMER CHEMICAL SOC; 2005. p. U202–U202.
• Lynch MD, Gill RT, Stephanopoulos G. Mapping phenotypic landscapes using DNA micro-arrays. Metabolic engineering. 2004 Jul;6(3):177–85.

In The News

• Duke Biomanufacturing Technology Licensed by Spinoff Company DMC (Jun 2, 2016 | )
• Michael Lynch: Bending Microbial Metabolisms to Generate New Chemicals (Nov 5, 2014 | Pratt School of Engineering)