Biotechnology Process Engineering Center
The Biotechnology Process Engineering Center (BPEC) as a National Science Foundation Engineering Research Center (NSF ERC), is a multi-disciplinary body with faculty members from the MIT Departments of Biology, Chemistry, and Chemical Engineering, the Division of Bioengineering and Environmental Health (BEH), and the Whitehead Institute for Biomedical Research, along with the University of Toronto Department of Chemical Engineering and the Brown University School of Medicine Liver Center. The mission of BPEC is to carry out research and education combining engineering with molecular biology, emphasizing a strong relationship with industry in its various activities. The goals of the Center are to perform cutting-edge, fundamental research in therapeutic gene and protein biotechnology based on contributions from, and interactions among, investigators from diverse relevant backgrounds.
The NSF celebrated the 15th Anniversary of the ERC program at their fall 2000 Annual Meeting. Since BPEC is the ERC class of 1985, it took an active role in this celebration. The BPEC remains committed to its core mission of fostering interdisciplinary research and education fusing engineering with molecular cell biology, with emphasis on strategic problem-solving and close interactions with the biotechnology industry. BPEC's NSF-supported Strategic Plan continues to focus on therapeutic gene biotechnology, with two major engineered-system objectives: an ex vivo approach employing genetically-engineered stem cells (BPEC Project Area A), and an in vivo approach employing targeted viral or synthetic vectors (BPEC Project Area B). This plan leverages and synergizes with our broader MIT mandate to catalyze research and education at the biology/engineering interface, prominently including the academic unit charged with creating and operating curricular degree programs in this area, the Division of Bioengineering and Environmental Health (BEH).
Educational programs of BPEC deal with the needs of undergraduates, graduates and industrial personnel. The goals of the educational programs are to provide integrated and broad bioengineering perspectives to the students. We have reenergized our Student Leadership Council with new members and activities. At the undergraduate level we now participate in the Biomedical Engineering Minor offered by BEH to students in all majors, while at the graduate level we likewise participate in the Bioengineering and Toxicology Ph.D. programs offered by BEH along with the traditional Ph.D. programs in Biology, Chemistry, and Chemical Engineering. We added a new degree program in BEH, the Masters of Engineering in Biomedical Engineering, which offers an opportunity for students to carry out thesis research in industry. In addition, National Institute of Health (NIH) Training Programs in Biotechnology and in Genomics are administered from the BPEC office, leveraging the NSF ERC to broader educational opportunities at the engineering/molecular-biology interface. Undergraduate research is achieved through the Undergraduate Research Opportunities Program (UROP) for MIT students and the Research Experience for Undergraduates (REU) for non-MIT students. Special one-week summer courses are offered to industrial personnel
Industrial activities and planning are coordinated through our Therapeutic Gene Biotechnology Industrial Consortium Advisory Board (TGB ICAB), supervised by our BPEC team of Industrial Liaison Officer (Matt Croughan) and Associate Industrial Liaison Officer (Jean-Francois Hamel). We are extremely pleased by the progress we have made this past year in our BPEC/industry partnerships. We more than doubled the size of our Industrial Consortium Advisory Board (ICAB), from seven to 16 members, and have received the most strongly positive ICAB SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis since the BPEC reconfiguration three years ago.
The DuPont-MIT Alliance (DMA) (a BPEC administrative umbrella) in Bio-Based Materials, is another facet of the BPEC mission to combine engineering with molecular biology. This Alliance provides $7M per year to MIT for a five-year period, and nicely extends the impact of the BPEC engineering/biology collaborative spirit to even broader reaches of the MIT campus and industry. The DMA funded 17 projects with 16 primary Principal Investigators (PIs) and 14 graduate fellowships during fiscal year 2001. Several faculty gave lectures at DuPont and two industrial short courses are in the planning stage for fiscal year 2002.
Statistically reporting, 141 personnel took part in the center's NSF strategic plan research activities during fiscal year 2001. This figure comprises of the following: 45 MIT Undergraduate worked as lab interns (i.e., UROP students), 12 non MIT undergraduates who participated in the center's NSF Research Education for Undergraduates Program (REU); 24 graduate students; 26 postdoctoral associates/fellows; 12 visiting scientists, engineers, industry researchers, eight administrative personnel, two other director level personnel and 12 faculty (some faculty served as executive directors).
Research — Therapeutic Gene Biotechnology
The overall objective of Project Area A, aimed toward the engineered system of genetically-engineered hematopoietic stem cells [HSCs], is to develop the knowledge-base and technology-base for generating and expanding HSCs in culture, transfecting them stably with particular therapeutic genes, selecting the HSCs with appropriate transgene integration and expression, and delivering them to a host. The three major Projects, being undertaken collaboratively among a number of the BPEC investigators (Daley, Griffith, Jaenisch, Lauffenburger, Lodish, Zandstra), are directed toward corresponding bottlenecks: A1—Control of HSC Proliferation; A2—Generation of HSCs from embryonic stem (ES) cells; A3—Transfection of ES cells.
The overall objective of Project Area B, aimed toward the engineered system of targeted gene delivery vectors for liver cancer, is to develop the knowledge-base and technology-base for specific ligand- targeted viral (mainly adenoviral) and non-viral (mainly synthetic polymer and peptide) vehicles carrying therapeutic genes, and delivering them to a host. The three major Projects, being undertaken collaboratively among a number of the BPEC investigators (Griffith, Langer, Lauffenburger, Sherley, Wands, Wittrup, Zhang), are directed toward corresponding bottlenecks: B1—Quantitative Assays of and Studies on Barriers to Gene Delivery; B2—Ligand-Based Targeting; B3—Synthetic Vehicles.
In total, then, comparing our progress and current status with the BPEC Strategic Plan Timeline, approaches, and methodologies have arisen. These new enhancements include:
- Proteomic and genomic approaches to understanding of new regulatory components for HSC proliferation;
- Tissue-engineered bone marrow bioreactors for HSC production;
- Studies of synergistic signaling by extracellular matrix and cytokines for differentiation of ES cells into HSCs;
- Mathematical model for intracellular processes involved in vector uptake, trafficking and expression;
- Application of synthetic polymer vehicles for gene delivery to the brain for neurodegenerative diseases; and
- Toxicogenomic approaches to adverse liver cell effects due to gene delivery vector uptake.
These are combining with our "on track" original plan to further accelerate our progress in our Strategic Plan toward creating engineered systems of: stem cell gene delivery therapies; and synthetic and targeted gene delivery therapies.
Our objectives remain to impact the education of undergraduate students, graduate students, and industrial personnel in their ability to work at the engineering/biology interface on important problems in biotechnology.
At the undergraduate level, our goal is to ensure the students are integrated into our research thrusts for both MIT (UROP) students and students from other institutions (REU and high schools). To expose the students to cross-disciplinary activities and teamwork, the projects are selected carefully and critically. BPEC provides initial experiences to undergraduates and encourages students to work in industry as internees. Our Industrial Liaison Officers and Education Coordinators contact companies associated with BPEC for summer undergraduate internships and the replies are then matched with BPEC's undergraduates for summer employment.
The Division of Bioengineering and Environmental Health (BEH) has now further enhanced its undergraduate curriculum aimed at integrating molecular cell biology with engineering, by developing a new five-year S.B./M.Eng. program in Biomedical Engineering (BME) to accompany the ongoing Biomedical Engineering S.B. Minor program. The BME Minor is MIT's first inter-departmental minor degree, available to undergraduates taking any S.B. Major degree at the Institute. The program comprises four subjects in Biomedical Engineering-two core subjects and two electives. These subjects require substantial preparation in science and engineering, and thus the minor is structured in the form of a Science Core (three subjects) and an Engineering Core (two subjects) which serve as prerequisites for the Biomedical Engineering subjects. The goal of the degree program is to educate students in how to apply fundamental engineering principles to solve challenging problems in biology and medicine. A common theme is the integration of individual components of a biological system to describe both the spatial and temporal organization of the system as a whole. The scale of this integration may be as small as molecules and cells or as large as organ systems or whole organisms. Students gain an appreciation of how to solve problems at these different scales by taking two core Biomedical Engineering courses. They can then pursue particular interests through the two restricted electives in Biomedical Engineering.
More than ever, cutting-edge research combining engineering with molecular biology concomitantly requires analogously novel educational programs, and BPEC is at the heart of the Division of Bioengineering and Environmental Health (BEH). BEH is a departmental structure within the School of Engineering charged with creating and administering educational and research programs that forge engineering with modern biology. Rather than focusing on a particular application field like most "biomedical engineering" departments being created across the country, BEH is focused on fostering a new discipline of biological engineering that will educate engineers to create technologies based on molecular biology whether the application area is medicine, environment, agriculture, materials, manufacturing, or so forth. BEH has initiated a new Bioengineering Ph.D. program with a novel core curriculum aimed at training this type of next-generation biotechnologist, alongside students trained in inter-disciplinary fashion in the MIT Departments of Chemical Engineering, Chemistry, and Biology-with all these programs intertwined through the NIH Training Programs in Biotechnology and Genomics also administered by BPEC.
During this past year, however, we have taken yet another major step forward in our undergraduate educational efforts by establishing a new five-year combined S.B./M.Eng. degree program in Biomedical Engineering. With this program, an MIT undergraduate can obtain his or her S.B. degree in any Major along with a M.Eng. degree in Biomedical Engineering within an integrated five-year period. The curriculum splices key aspects of the BME Minor with some of our Bioengineering (BE) Ph.D. core subjects, and adds an independent research project leading to a M.Eng. thesis.
One especially exciting opportunity that the M.Eng. leads to is the possibility of students carrying out their thesis research in an industrial setting, such as in a laboratory at one of our Industry Advisory Consortium Board (ICAB) partner companies. We are beginning to pursue discussions with some of our ICAB members about ways to move along this very attractive avenue.
At the graduate level, one of the goals of BPEC is to provide research experience related to the center's research thrusts. We ensure that the research is conducted with a spirit of teamwork and inter-disciplinary input. This is achieved by joint faculty advisors on the doctoral thesis and/or thesis committee members from different departments and disciplines. To provide industrial perspectives on the students' training program, industrial personnel are often members of doctoral thesis committees. In addition, our industrial collaborators have also participated in course lectures, both for undergraduates and graduates. To further integrate our graduate students into the industrial environment, our students are part of our technology transfer activities to industry. In this capacity, the students obtain valuable perspectives on industrial research and development and, at the same time, act as the conduit to testbeds at industrial sites. Our graduate students also actively participate as teaching assistants (TAs) in the courses which are related to the center's research thrusts. This training provides experience in teaching in case the students are planning careers in academia.
Through the efforts of the BPEC, the Interdepartmental Biotechnology Training Program successfully completed its 12th year. Twenty-four Training Faculty participate from the Departments of Biology, Chemistry, Chemical Engineering, and Mathematics, and the Division of Bioengineering and Environmental Health. This training grant is funded by NIH National Institute of General Medical Sciences (NIGMS) with a total of 20 pre-doctoral trainees and recently received a new award for an additional five years.
The mission of BEH is to educate leaders, and generate and communicate new knowledge, at the interface between engineering and biology. The central premise of BEH is that the science of biology will be as important to technology and society in the next century as physics and chemistry have been in the one now ending. Therefore, engineers and scientists must be educated people who: can apply their measurement and modeling perspectives to understanding how biological systems operate, especially when perturbed by genetic, chemical, mechanical, or materials interventions, or subjected to pathogens or toxins; and can apply their design perspective to creating innovative biology-based technologies in medical diagnostic, therapeutic, and device industries, or in non-health-related industrial sectors such as agriculture, environment, materials, or manufacturing. That is, we must educate a new generation of people who can solve problems using modern biotechnology, emphasizing an ability to measure, model, and rationally manipulate biological systems. Hence, a key function of BEH is to create and support curricula in which biology and engineering are taught as synergistically as possible, and the new BE PhD program is aimed directly toward accomplishing this function. The new program is designed to bring together engineering and biology in as fundamental a manner as possible. Stated broadly, it will educate students to use engineering principles in the analysis and manipulation of biological systems, to solve problems across a spectrum of important applications. Accordingly, the curriculum will emphasize fundamental concepts more than particular applications. By learning to advance both engineering and biological knowledge, it is anticipated that the graduates will be well positioned to contribute to many areas of research in both academic and industrial settings.
In its initial year of its operation, 1999-2000, 11 outstanding first year bioengineering graduate students were brought in; our goal for the foreseeable future is to recruit ~10-15 new graduate students per year. The typical entering students hold a B.S .(or M.S.) degree in an engineering discipline (typically Biomedical, Chemical, Electrical, Mechanical, Materials Science, or Computer Science). During their first year, the students pursue a unified core curriculum, in which approaches from the various engineering disciplines will be used to examine biological materials and organisms over a wide range of length and time scales. The core curriculum, which will consist largely of subjects not offered previously at MIT, will be the hallmark of the new program. The program will have its own Ph.D. qualifying exams, the written part of which will be based on the core curriculum. To enhance depth and breadth, the core subjects will be supplemented by electives in the biological sciences and engineering. A student's research will ordinarily begin near the end of the first year, leading after approximately five years of total residence to a completed Ph.D. thesis.
Leadership in The Field and Involvement with Others
There are many indicators noting how BPEC is recognized and respected as a national center to the professional communities. One measure on the outreach and leadership of the ERC faculty is the invited presentations to the various biotechnology communities. The 12 faculty members in the BPEC during fiscal 2001 participated in the following categories:
|Seminars at Universities||=45|
|Seminars at Industry||=22|
|Presentation at National and International Conference and Symposium||=28|
|Workshop/Short Course Parcipitation||=2|
A significant number of the BPEC faculty have been recognized by invited distinguished lectureships across the country, major awards and prizes, and fellow election in professional societies. It is our opinion the data presented above demonstrates the Center's outreach and leadership in the field of biotechnology.
An indicator of outreach from BPEC is its collaborative efforts with other universities in education and/or research.
BPEC has entered into a partnership with the bioengineering-related ERCs at Georgia Tech and University of Washington to co-sponsor an annual Workshop; in March 2001; it was held at Hilton Head, SC. This partnership is fostering positive interactions among these three bioengineering-related ERCs, and indeed MIT and Georgia Tech are developing plans to identify new collaborative research projects under joint ERC auspices. An example of this collaboration is the anticipation to carry out a partnership in Education and research. With GTEC as the lead center, a supplemental NSF Partnerships in Education and Research proposal has been awarded for summer 2002.
BPEC's objectives remain to impact the education of undergraduate students, graduate students, and industrial personnel in their ability to work at the engineering/biology interface on important problems in biotechnology. In order to carry out these objectives, BPEC plans to continue its outreach involvement in undergraduate and graduate education through the BEH, NIH Training Grants, UROP and NSF REU programs, and industrial internships. At the K–12 level, BPEC has started collaborations with the Science Coordinator for the Cambridge School Department and has received funding from NSF for a Research Experience for Teachers award in collaboration with Johns Hopkins University. In addition, through collaborative and team efforts continue its research focus in gene therapeutics.
Planned personnel changes for fiscal year 2002 include the participation of Professor Leona Samson, a new toxogenomics BEH faculty member.
We have added a new investigator, Professor James Sherley of BEH, who is an expert in tissue cell kinetics (and, moreover, is a member of an under-represented minority group). We have recently hired a new Information Systems Administrator to oversee all of BPEC's computer systems.
More information about this the Biotechnology Process Engineering Center can be found at http://web.mit.edu/bpec/.