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Chemical & Biochemical Engineering Research

Research at Thayer School based on chemical engineering fundamentals involves faculty and students with diverse backgrounds—reflecting the fact that engineering and scientific subdisciplines overlap. Students have opportunities to draw from several intellectual traditions in both coursework and research. Students with preparation in a variety of science and engineering subdisciplines are encouraged to contact designated faculty about the possibilities for contributing to specific projects.

Applied Microbiology

Fundamental aspects of microbial cellulose utilization are actively being studied with an emphasis on features that are not exhibited by cell-free cellulase systems. Such features include bioenergetics and substrate uptake, enzyme-microbe synergy, substrate adherence and capture, control of cellulase synthesis, selection, competition, and microbial ecology. Our focus is on anaerobic microorganisms of potential utility for consolidated bioprocessing including but not limited to Clostridium thermocellum.
(Faculty contact: Lynd)

Biomass Processing

Improved conversion technologies for plant biomass—the only foreseeable sustainable source of organic fuels, chemicals, and materials—have outstanding potential to address pressing societal challenges. A comprehensive effort in this area encompasses applied microbiology, metabolic and cellular engineering, kinetics and reactor design, process design, and resource and environmental analysis.
(Faculty contact: Lynd)

Complex-fluid & Bio-fluid Dynamics

Biological fluids are living, complex—i.e., microstructured—fluids. Nature's designs present fascinating examples of soft materials—biopolymers (DNA and proteins), self-assembled lipid bilayers (cell membranes), and physiological fluids (blood). Fluid flow and biological function are intricately interwoven in the fabric of life. Mechanical forces such as fluid shear stress can modulate gene and protein expressions and hence cellular functions. Collective dynamics of swimming microorganisms is important in ecological issues such as algae blooms. Particular projects in the area of biological fluid dynamics include cell shape transitions in capillary flows (with application to quantitative modeling of microcirculation) and suspensions of swimming cells (with application to quantitative understanding of plankton dynamics).
See also Interfacial Fluid Mechanics and Particulate Flows
(Faculty contact: Vlahovska)

Fermentation Science

High cell density fermentation is important for the production of most bio-therapeutics which is conducted in highly controlled fed-batch processes. Commercial yeast- and E.coli-based fermentation processes often reach cell-densities in excess of 50g/l in fed-batch culture. Our laboratory has developed processes for the high cell density cultivation of Ralstonia eutropha allowing us to reach cell densities of over 150g/l and the expression of recombinant proteins at titers exceeding 10g/l. Much of this is achieved by implementing computer controlled feeding algorithms.
(Faculty contact: Gerngross)

Fermentation studies are used as a tool to investigate several aspects of microbial cellulose utilization and kinetics and reactor design, as well as to characterize and improve performance of recombinant microorganisms. We have distinctive facilities and expertise in the area of fermentations systems for insoluble cellulosic substrates.
(Faculty contact: Lynd)

Kinetics & Reactor Design

Cellulose hydrolysis mediated by cells and/or cellulase enzymes is complex, poorly understood, and exhibits kinetics very different from soluble substrates. Development of kinetic models is underway at several levels of aggregation, with the objective to structure and test understanding as well as design and optimization. Features incorporated into such models include: adsorption exhibiting saturation in either substrate or enzyme, substrate reactivity that declines with increasing conversion, the changing rate of reaction of particle populations of different ages over the time they spend in the reactor, and the presence of functionally-distinct cellulase activities.
(Faculty contact: Lynd)

Metabolic & Cellular Engineering

Cell-based protein purification systems offer advantages over conventional protein purification approaches which rely mostly on chromatographic methods to stepwise enrich for a desired protein of interest. We are developing approaches by which cells are engineered to produce their own affinity matrix to selectively sequester a desired recombinant protein. This allows for the expression and affinity purification of desired proteins in a single host, thereby obviating the need for external chromatographic purification.
(Faculty contact: Gerngross)

Cellular engineering of protein expression hosts provides the ability to modify proteins in a site specific and controlled fashion—something increasingly important for the development of therapeutic proteins. We are developing methods by which cells are genetically engineered to incorporate sugars on a recombinant protein in a site-specific sequence dependent manner. Once a sugar is positioned on a given protein, conventional chemical modification such as PEGlylation can be used to further modify the protein and improve its therapeutic properties.
(Faculty contact: Gerngross)

Consolidated bioprocessing (CBP) is a potential breakthrough in low-cost processing of cellulosic biomass in which biological conversion is consolidated into a single process step without added cellulase enzymes. Development of CBP-enabling microorganisms can proceed either engineering cellulolytic microbes to improve product titer and yield, or engineering organisms that have high product yields and titers so that they can utilize cellulose and other biomass components. Both strategies are actively under investigation in collaboration with Mascoma Corp.
(Faculty contact: Lynd)

Novel Protein Expression Systems

An alternative to E.coli-based protein expression has been developed based on the soil bacterium Ralstonia eutropha. This bacterial host can be grown to cell densities in excess of 150g/l in ultra high cell density culture and allow for the recovery of proteins that are prone to inclusion body formation in E.coli. Specific model proteins have been expressed at levels 100 fold higher than in E.coli thereby providing the impetus for further developing Ralstonia eutropha for the production of therapeutic proteins including monoclonal antibodies and peptides.
(Faculty contact: Gerngross)

Humanization of glycosylation in yeast enables the use of yeast-based protein expression systems which offer inherent advantages over conventional mammalian cell culture. By engineering yeast-based systems to perform human-like glycosylation fully-humanized therapeutic proteins can be produced in these glyco-engineered hosts. (See also: www.glycofi.com)
(Faculty contact: Gerngross)

Process Design

Current and advanced processes converting biomass into energy are designed using the process simulation package aspenONE®. These designs are used to evaluate economics and materials flows (e.g., feedstock demand, waste products), to identify research priorities, and to quantify the impact of process improvements in terms of both economic and environmental metrics. "Biorefineries" producing co-products such as animal feed and electricity in combination with biologically-based production of fuels, chemicals, and materials are of particular interest.
(Faculty contact: Lynd)

Protein Engineering

Although current research has a decidedly applied emphasis, results also provide insights into basic immunology, enzymology, mechanisms of molecular evolution, and other fundamental aspects of biomolecular science. Students working in the protein engineering laboratory will develop a broad understanding of relevant scientific disciplines and will be positioned to thrive at the cutting edge interface of engineering, chemistry, and biology.

Enzyme therapeutics for treatment of complications associated with the genetic disease cystic fibrosis are being investigated in conjunction with the Cystic Fibrosis Foundation Research Development Program at Dartmouth Medical School. Future projects in the biotherapeutic area will utilize not only enzymes, but also antibodies and peptides as agents for treating disease conditions.
(Faculty contact: Griswold)

Glyco-engineering of proteins is being developed as a method to control the composition of glycans on glycoproteins. Such methods are of great importance in the biopharmaceutical industry because glyocoproteins constitute over 60% of all approved therapeutic proteins; and the therapeutic properties of many glycoproteins strongly depend on the composition of their glycans.
(Faculty contact: Gerngross)

Hydrolytic enzymes are of industrial interest, specifically as catalysts in the synthesis of enantiomerically pure pharmaceutical intermediates. We are exploring novel strategies for high throughput screening of esterases, lipases, and alkyl sulfatases.
(Faculty contact: Griswold)

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