Link to article describing TBE Program in the MSU Graduate Post

Link to PowerPoint Presentation on TBE Program

Purpose and Objectives

The purpose of the Multidisciplinary Training Program on Technologies for a Biobased Economy (TBE) is to produce a diverse group of Ph.D. scientists and engineers who have broad training related to biobased industrial product formation, have strong research skills, and are able to work effectively in multidisciplinary teams.  The specific objectives of the program are (1) to provide a multidisciplinary graduate education focussed on the conversion of renewable raw materials into commercial products; (2) to help students develop the professional skills needed to work effectively in multidisciplinary research teams; (3) to involve industry in the educational process so as to maximize the relevance of the training, and (4) to produce graduates versatile enough to succeed in the academic, private, nonprofit, and governmental sectors.

Motivation for the Program

The U.S. agricultural, forestry, life sciences and chemical communities have developed a strategic vision for using crops, trees and agricultural residue to manufacture industrial products, and have identified major barrier to its implementation. Recently, several of the world's largest chemical companies, including DuPont, Monsanto, Dow, and Cargill, have announced major new businesses based on the life sciences instead of traditional petrochemical processing. Moreover, DuPont and Monsanto have recently invested $12.5 billion to acquire expertise in agricultural biotechnology . 

A major impediment to the successful development of a biobased products industry (BPI) is the lack of an educational infrastructure to provide broadly trained Ph.D.s able to integrate knowledge from diverse science and engineering fields. A recent NRC study conducted to identify research and commercialization needs to support US biobased industries concluded that chemical engineers need to be better trained in the biological sciences, and that biologists need to be trained in process engineering, so that the biologists and engineers could work together effectively to establish the technical infrastructure for developing, manufacturing, and using biobased products. The proposed training program is specifically designed to provide such multidisciplinary training. It also emphasizes close interactions with industry to maximize the industrial relevance of the training and to facilitate industrial recruitment of the trained students. 

Training Faculty

The multidisciplinary Training Faculty assembled for this program provides Fellows access to (1) nationally recognized research expertise related to biobased industrial products, (2) a multidisciplinary selection of research specializations that cuts across all of the essential elements of the BPI, and (3) mentors having outstanding teaching credentials. The group includes two members of the NRC Committee on Biobased Industrial Products5, a winner of the Presidential Green Chemistry Award, and a winner of the Charles D. Scott Award. These latter two awards recognize the nation's most outstanding researchers in biobased industrial products. 

In addition to their research accomplishments, most of the Training Program Faculty have won teaching awards and/or have worked together to develop innovative, multidisciplinary training programs. Brief descriptions of the Training Faculty are given below. 

· Kris Berglund, Professor of Chemical Engineering and Chemistry. Dr. Berglund's research includes both fermentation and separations. He directed the MSU Crop and Food Bioprocessing Center from 1989 to 1999, was awarded an MSU Teacher Scholar Award, an MSU Distinguished Faculty Award, and was a Fulbright Scholar at the Technische Universiteit, at Delft, the Netherlands. He is President of LEC TECH, a small company that produces commercial products from biobased raw materials. He is Industrial Liaison for the Program. 

· Daina Briedis, Associate Professor of Chemical Engineering. Dr. Briedis's scholarship relates to the application of learning theory in the classroom and assessment of educational programs. She serves as an ABET evaluator for the new Engineering Criteria 2000 and has received several teaching awards, including the State of Michigan Teaching Excellence Award, the MSU Teacher-Scholar Award, the Engineering College Withrow Teaching Excellence Award, and the Golden Key National Honor Society Outstanding Teaching Award. She is Assessment Coordinator of the Program. 

· Bruce Dale, Professor of Chemical Engineering. Dr. Dale studies the chemical, enzymatic and biological conversion of cellulosic plant matter to fuels, chemicals and materials. The AFEX technology he developed is being commercialized to help convert biomass into fermentable sugars. He is a recipient of the Charles D. Scott Award, Chair of MSU's Chemical Engineering Department, and Director of MSU's Crop and Food Bioprocessing Center. As Co-Chair of the National Research Council Committee on Biobased Industrial Products, he co-authored the previously cited NRC study5. He is a Co-Director of the Program. 

· John Frost, Professor of Chemistry. Dr. Frost's lab uses genetic engineering to construct new metabolic pathways in microbes and plants. In 1998, he was awarded a Presidential Green Chemistry Award for his research accomplishments in biobased chemicals production. 

· Carl Lira, Associate Professor of Chemical Engineering. Dr. Lira's laboratory applies thermodynamic theory to develop separations processes based on supercritical extraction and adsorption. He was recently awarded a USDA SBIR grant for production of a biobased specialty chemical and has been awarded the College of Engineering Withrow Teaching Excellence Award and the Amoco Foundation Excellence in Teaching Award. 

· Ramani Narayan, Professor of Chemical Engineering. Dr. Narayan's laboratory is focused on the production of biodegradable materials from starch and plant oils. Examples include polymers for film and injection molded plastics applications based on poly(lactic acid), starch-polyester blends, and modified starch esters. Starch foam noodles developed in his laboratory are being marketed through KTM Industries. A new thermoset matrix based on functionalized soybean oil has been synthesized, and a biofiber-reinforced natural soybean based thermoset composite is being developed. 

· John Ohlrogge, Professor of Botany and Plant Pathology. Dr. Ohlrogge's laboratory applies genetic and metabolic engineering to plant cells to economically produce lipophilic molecules. He is Co-Director of the National Plant Lipid Cooperative and Co-Director of a multiuniversity research consortium on plant lipid production that was recently awarded a ten-million dollar grant from Dow Chemical company. 

· Jack Preiss, Professor of Biochemistry. Jack Preiss' laboratory is concerned with mechanisms involved in synthesis of starch and its regulation. He is Director of the Starch Bioengineering Group in the Department of Biochemistry. He has received numerous research awards, including the ACS Charles Pfizer Award in Enzyme Chemistry, the 1990 Alsberg-Schoch Memorial Lectureship Award of the American Association of Cereal Chemists, the 1992 Award of Merit of the Japanese Society of Starch Science, and the MSU Distinguished Faculty Award. 

· Mark Worden, Professor of Chemical Engineering. Dr. Worden's research focuses on fermentation optimization. He has received an MSU Teacher-Scholar Award, and a College of Engineering Withrow Teaching-Excellence Award. Dr. Worden is Director of the Training Program. 

· Gregory Zeikus, Professor of Biochemistry. Dr. Zeikus' laboratory specializes in the design and control of enzyme and whole-cell biocatalysts that must function under harsh conditions. He is President and CEO of MBI International, whose mission is to commercialize bioprocesses based on renewable resources. He was a member of the National Research Council Committee on Biobased Industrial Products5 

The research component of the Training Program will consist of (1) completion of a multidisciplinary dissertation research project relevant to the biobased products industry and (2) completion of an industrial internship lasting at least one-semester. The topic of the dissertation research project will be chosen by the student, in consultation with his or her Ph.D. committee. The Ph.D. committee, which will contain at least two members of the TBE Training Program Faculty and one industrial representative, will ensure that the project satisfies the objectives of the research program. Satisfactory projects would be multidisciplinary and would represent collaborations between the research groups of two or more TBE Training Program Faculty. . 

Research Foci of the Training Faculty

The research programs of the Training Faculty complement one another to provide particular strength in four focus areas. As described below, these focus areas are well aligned with the "barrier areas" that currently limit commercial development in the biobased products industry. 

· Plant Science and Production (Ohlrogge, Frost). From an environmental perspective, the best starting material for synthesis of chemical products is carbon dioxide (CO2), which is a greenhouse gas implicated in global warming. Collaborative research between the Frost and Ohlrogge groups is examining how aromatic chemicals can be synthesized in the chloroplasts of intact plants from carbon dioxide. Plants commit a large percentage of the CO2 they fix into biosynthesis of aromatics (i.e. lignin). Tapping this abundant carbon flow is the goal of the collaborative research program. The aromatics or precursors to aromatics targeted for chloroplast-based synthesis using intact plants are molecules for which microbial syntheses have been, or are being, elaborated by the collaboration between the Frost and Worden groups. Such efforts will allow direct comparison of microbes with plants as biocatalytic platforms for industrial chemicals. 

In addition to basic research on plant fatty acid and triacylglycerol biosynthesis, Dr. Ohlrogge's lab is involved in genetic engineering of plant oils to provide feedstocks for the chemical industry. Several projects in his lab are designed to identify genes involved in the production and accumulation of high-value fatty acids such as petroselinic acid and cyclopropane fatty acids. The Ohlrogge lab is interacting with the Chemical Engineering Department to evaluate biorefining strategies for high-value oil recovery. Plant properties can be tailored through genetic engineering to facilitate product recovery. The Ohlrogge lab is also collaborating with the Frost lab to transfer bacterial genes for aromatic biosynthesis (e.g., catechol and protocatechol) into oilseeds. 

· Plant Primary Processing (Dale, Lira, Preiss, Berglund) Chemical intermediates contained in plant matter are often difficult to recover because they are trapped in the structural polymers (cellulose and lignin) that give the plant strength. Primary processing is required to break down these polymers and liberate the chemicals for subsequent bioconversion and biorefining steps. Dr. Dale's laboratory is developing methods for recovering protein and other valuable products from plant materials during their processing to industrial products such as fuels, chemicals and polymers. Methods are also being developed to increase sugar yields obtained through enzymatic hydrolysis of lignocellulosics. The Dale lab will collaborate with the Ohlrogge lab to develop means of isolating polymer feedstocks from oilseeds and with the Frost and Worden labs to generate mixed sugars for fermentation from corn fiber and corn stover. Dr. Preiss' lab has been studying the regulation of starch synthesis and has isolated mutants in bacteria that affect the regulatory properties of the enzyme ADP-glucose pyrophosphorylase (ADPGlc Ppase). When the allosteric mutant enzyme gene is transformed into plants their production of starch can be increased by about 60%. The properties of starch dictate its economic use, and the specific properties of starch are dependent on its structure, mainly its degree of branching. The manipulation of starch structure is also an important endeavor. The degree of branching is determined by the properties of branching enzyme (BE), and another endeavor in the Preiss lab is to alter the properties of BE through recombinant DNA methodology. Dr. Lira's lab is developing separations techniques for hydroaromatics and organic acids. His knowledge of phase equilibria will help guide the selection and scale-up of separation processes. Collaboration will be an integral part of the development of recovery techniques to understand the identity and properties of components in the complex feed and product streams. Dr. Lira's lab has facilities for conventional separation techniques, as well as low-temperature separations, such as supercritical extractions (up to 2L/batch) and solid phase extractions. One recovery technique under development is the regeneration of adsorbents using compressed CO2. 

· Processing: Conversion and Separation (Frost, Zeikus, Worden, Narayan, Berglund). Primary processing yields chemical intermediates, such as fermentable sugars, that must then be upgraded to higher value products through bioconversion technologies. "Biorefineries" are envisioned that would fractionate the plant matter into its components and then convert each component into a salable product. Collaboration between the Frost, Worden and Ohlrogge groups focuses on the bioconversion of sugars into aromatic chemicals. This approach is designed to replace carcinogenic benzene as a starting material for synthesis of aromatic chemicals with environmentally friendly starting materials such as glucose, xylose, arabinose, glycerol, and CO2. Research in the Frost group has focused on genetic manipulation of microbes to create biocatalysts that mediate conversion of polyol starting material directly into aromatics and hydroaromatics. Collaborative efforts between the Frost and Worden groups have focused on optimization of these fed-batch fermentations. The extensive fermentation facilities available in the Biochemical Engineering Teaching Laboratory managed by Dr. Worden will allow the fermentations to be scaled up from 1 L to 400 L. Dr. Berglund's laboratory is developing a number of enabling technologies for the economic production of chemicals from renewable resources, including new separation schemes for fermentation products and value-added processing of fermentation-derived platform molecules. Of particular interest is the integration of the separation scheme with a subsequent chemical reaction step without isolation of intermediates. This approach allows biobased chemicals to be cost effective. Dr. Berglund collaborates with Dr. Frost in the integration of fermentation with downstream processing. The recycling of biochemical cofactors (i.e., ATP and NADH/NADPH) can limit both the rate and yield of products formed by fermentation or whole-cell biotransformation systems. Dr. Zeikus has developed novel electrochemical bioreactor systems that use the electron carrier neutral red, a graphite felt electrode, and electricity to recycle the cofactors and achieve faster reaction rates and higher end-product yields. This approach is being applied to produce biobased chemicals. 

· Utilization: Novel materials and process modeling (Narayan, Lira, Dale, Worden). The Narayan lab will work with the Preiss lab to develop novel starch-based polymers from specialty starches, starch esters and blends of starch esters with aliphatic polyesters. The Narayan and Ohlrogge labs will collaborate on the development of new polymers based on plant-derived lipids. Commercial viability of biobased industrial processes requires that the global economic and environmental profiles be favorable. Dr. Dale's laboratory is developing economic models for plant conversion systems and life cycle analysis data for products derived from plants. The Dale and Narayan lab will work with each of the laboratories in the project to produce a life cycle analysis for selected products. Separation-process design will be modeled to guide selection of separation techniques, and also to guide manipulation of key parameters that affect separations, such as temperatures, pressures, and flowrates. Often, such calculations can efficiently identify key barriers to separations, and provide guidance to the Genetic Engineering and Primary Processing Teams as to the critical steps that govern economic viability of the processes. Dr. Lira will utilize state-of-the-art process simulation software from ASPENTECH for process design calculations and economic evaluations. Dr. Worden will use SuperPro Designer software (Intelligen, Inc.) to supplement the ASPENTECH simulations. Superpro Designer has extended capabilities for modeling bioprocess unit operations. 

Students participating in the Program will be required to satisfy the Ph.D. requirements of their home department as well as specific Program requirements. The Program requirements include (1) course requirements intended to ensure a cross-disciplinary knowledge base, (2) completion of a College Teaching Certificate Program so the Fellows can disseminate their knowledge effectively after graduation, and (3) an industrial internship to provide the Fellows with an industrial perspective. 

Course Requirements:  Program course requirements include (1) the Multidisciplinary Bioprocessing Laboratory (MBL) course recently developed at MSU, (2) courses required for the College Teaching Certificate Program and (3) six credits of courses taken from outside the student's college to provide sufficient breadth of training. The MBL course teaches students from different engineering and bioscience fields to conduct research effectively in multidisciplinary teams. The student teams work closely with a research mentor from the research lab of one of the participating faculty on a semester-long, multidisciplinary research project. The course culminates with oral and written presentations of the research results. Additional information about the course may be found on its web page (http://www.egr.msu.edu/che/html98/classes/491). The College Teaching Certificate Program requires is described in more detail below. The six credits from outside the college will be chosen with input from the student's Graduate Committee and the TBE Executive Committee (Worden, Briedis, Dale, and Ohlrogge). Recommended Engineering courses include Biochemical Engineering (CHE 481), Advanced Biochemical Engineering (CHE 882), Foundations of Chemical Engineering I (CHE 804) and Foundations of Chemical Engineering II (CHE 805). These latter two courses are used by the Chemical Engineering Department and the National Technological University to give students with B.S. degrees in fields other than chemical engineering an overview of the field, so that they can begin graduate studies in chemical engineering. Thus, these courses are ideal cross-training supplements for students in Biochemistry, Chemistry, Botany and Plant Pathology. Drs. Worden, Briedis, Lira, and Dale teach all of these courses. Recommended courses in Biochemistry include Molecular Biology (BCH 801), Protein Structure and Function (BCH 804), Biochemical Mechanisms and Structure (BCH 821), and Plant Biochemistry (BCH 864). Recommended courses in Botany and Plant Pathology include Plant Molecular Biology (BOT 856), Plant Growth and Development (BOT 865), and Molecular and Biochemical Plant Pathology (BOT 881). Recommended courses in Chemistry include Structure and Spectroscopy of Organic Compounds (CEM 845), Advanced Organic Chemistry (CEM 851), Computer-Based Scientific Instrumentation (CEM 838), Kinetics and Spectroscopic Methods (CEM 882) and Biocatalysis (CEM 956). 

College Teaching Certificate Program Requirements:  The College Certificate Program provides skills needed to effectively teach technical concepts.  Such skills would allow the Fellows to efficiently disseminate their knowledge to others after graduation, thereby leveraging the benefit of the Program to the emerging biobased product industry.  Both the College of Natural Science and the College of Engineering have developed versions of the College Certificate Program. Additional information about these versions may be found at their web sites, http://www.msu.edu/user/gradschl/teaching.htm, and http://www.egr.msu.edu/~somerton/CTC_Program/, respectively. The Engineering version requires a one-credit course on the theory and practice of teaching and a mentored teaching experience. 

Industrial Participation in the Program

An Industrial Advisory Committee (IAC) helped plan the structure of the Training Program and will participate in its implementation in four ways. First, the IAC will help arrange internship opportunities for the Fellows. Each Fellow will be required to complete an industrial internship of at least one semester. During these internships, the Fellows will be encouraged to perform research relevant to his/her dissertation topic and possibly to develop a proposal for commercial development of a new biobased product or process by the company. Second, industrial speakers will be invited to give seminars in the TBE Seminar course. Through these seminars, the Fellows will benefit from the speakers' real-world experiences and insights. Third, an industrial representative will serve on the Ph.D. committee of each Fellow. At MSU, industrial representatives are commonly given adjunct faculty status for this purpose. Fourth, the industrial participants will be asked to provide feedback on the effectiveness of the training program. Because the BPI is a primary constituent of the training program, such feedback is an important aspect of Training Program's assessment process. Current members include IAC include Dr. Henry Kohlbrand, Global R&D Director of Industrial Biomaterials Platform at Dow; Dr. Robert Dorsch, Director of Biotechnology Development at DuPont; Dr. Donald Johnson, Vice President of Discovery Research at the Grain Products Corporation (CPC); Dr. Doug Cameron, Director of Biotechnology at Cargill; and Mr. Mat Peabody, CEO of Applied CarboChemicals.  Additional members will be added to extend the range of industries participating in the Program. 

1) Plant/Crop-based Renewable Resources 2020, URL: http://www.oit.doe.gov/agriculture/pdfs/vision2020.pdf
2) The Technology Roadmap for Plant/Crop-Based Renewable Resources 2020, URL: http://www.oit.doe.gov/agriculture/pdfs/ag25942.pdf
3) Thayer, A.M. "Living and Loving Life Sciences," Chem & Eng News, Nov. 23, 1998, 17-24.
4) Thayer, A.M. "Chasing the Innovation Wave," Chem & Eng News, Feb. 8, 1999, 17-22.
5) National Research Council, Committee on Biobased Industrial Products, "Biobased Industrial Products: Priorities for Research and Commercialization," National Academy Press, Washington, D.C., August 3, 1999. 

Bioprocessing @ Michigan State University