Research

From carbon-negative fermentation to cell & gene therapy.

The group works across two complementary areas of modern molecular biotechnology and synthetic biology: microbial biotechnology and mammalian cell & gene-therapy bioengineering. Seemingly orthogonal, the two are complementary and synergistic, sharing tools and ideas.

Pillar I

Microbial Biotechnology & Synthetic Biology

Solventogenic and acetogenic clostridia, non-photosynthetic CO2 fixation, synthetic methylotrophy, and syntrophic microbial communities, for sustainable fuels, chemicals, and materials.

Carbon-Negative Fermentation

Metabolic engineering and industrial biotechnology of clostridia for biofuels and advanced biorefinery products from CO2 and sugars.

  • Solventogenic and acetogenic clostridia paired in syntrophic co-cultures so the CO2 and H2 from one partner are fixed by the other, giving mixotrophic (sugar + gas) fermentation with superior carbon yields.
  • Non-photosynthetic CO2 fixation raising titers of solvents such as butanol, isopropanol, and hexanol.
  • Routes to sustainable manufacturing that valorize industrial CO2 rather than fossil feedstocks.

Genomics & Regulatory Networks

Experimental and computational genomics to study and reprogram prokaryotic sporulation and stationary-phase phenomena.

  • RNA-seq with in-house pathway- and signaling-analysis tools to map regulatory programs.
  • Gene-expression, genome-editing, and RNA-based synthetic-biology tools for solventogenic and acetogenic Clostridium species.
  • 13C-metabolic flux analysis to resolve core metabolism and guide rational strain design.

Clostridial Stress Response

Unraveling the links between sporulation, solvent production, and stress response in solventogenic clostridia.

  • How cells sense and adapt to solvent toxicity, oxidative stress, and other bioprocess stresses.
  • Engineering robustness as a multigenic trait to raise product titers and process stability.
  • Connecting the sporulation program with solvent formation and stress tolerance.

Synthetic Methylotrophy

Engineering E. coli to use one-carbon feedstocks, expanding the range of sustainable routes to fuels and chemicals.

  • E. coli-based synthetic methylotrophy converting one-carbon substrates such as methanol into central metabolism.
  • Pathway design and flux balancing to make one-carbon utilization efficient and stable.
  • Complements clostridial CO2 fixation as a second carbon-efficient manufacturing platform.

Microbial Interactions & Microbiomes

Fundamental cell-to-cell interactions in complex, multi-component microbial communities, and what they reveal about microbiomes.

  • Syntrophic conditions give rise to previously unknown phenomena, including heterologous cell fusion.
  • Intercellular exchange of proteins and nucleic acids via naturally released prokaryotic extracellular vesicles.
  • Relevance to human, animal, and environmental microbiomes.

Pillar II

Cell & Gene-Therapy Bioengineering

Engineering mammalian and stem cells (and the extracellular vesicles they release) for regenerative medicine, cell & gene therapies, and robust biomanufacturing.

Stem-Cell Bioengineering

Hematopoietic stem-cell differentiation, plasticity, and hematology for regenerative medicine and cell & gene therapy.

  • Understanding stem-cell development and its clinical applications.
  • Genetic and genomic tools, plus experimental animal studies, to examine human stem- and progenitor-cell development.
  • Advanced culture and assay methods, including flow cytometry/FACS and advanced microscopy.

Megakaryocytes, Platelets & Extracellular Vesicles

The biology of megakaryopoiesis and megakaryocytic extracellular vesicles (MkEVs) for therapy and cargo delivery.

  • Megakaryopoiesis and in vitro platelet production for transfusion therapies.
  • Megakaryocytic extracellular vesicles (MkEVs) and synthetic bio-nanoparticles for cell & gene therapies.
  • Using MkEVs for cargo delivery to hematopoietic stem cells.

Cell-Culture Biomanufacturing

From the fundamentals of bioreactor hydrodynamics to models for continuous manufacturing.

  • Seminal work on mixing, agitation, and hydrodynamics in cell-culture bioreactors.
  • Dissecting and modeling perfusion bioreactors for continuous biomanufacturing.
  • Multiparametric flow cytometry/FACS applied to cell-culture bioprocessing.

Patents & IP

Patents

Technologies invented in the lab, protected and available for translation. Most entries link to the public patent record.

Prov. 63/553,918 Provisional

Enhancing hydrogen and carbon dioxide use in acetogenic monocultures and cocultures

E. T. Papoutsakis, Y. Seo, N. Willis

Filed Feb 15, 2024 · Provisional application

Prov. 63/461,018 Provisional

Engineered extracellular vesicles and uses thereof

E. T. Papoutsakis, S. Das, J. Belliveau

Filed Apr 21, 2023 · Provisional application

Prov. 63/425,554 Provisional

Production of chemicals and bioenergy from sugars, one-carbon molecules and gases using engineered mixotrophic consortia for enhanced CO2 fixation

E. T. Papoutsakis, H. Seo, J. Otten, N. Willis, J. Hill

Filed Nov 15, 2022 · Provisional application

See the science in print