Workshop on Modeling in Biochemical Engineering October 11-12, 1996

A Conference on Modeling in Biochemical Engineering was held on the Minneapolis Campus of the University of Minnesota over the weekend of October 11-12, 1996. A select group of leading biochemical engineers and biologists gathered to discuss the current status and future perspectives of modeling and computation in this field. A further purpose of this meeting was to honor University of Minnesota Professor A.G. Fredrickson of the Department of Chemical Engineering & Materials Science for outstanding contributions made in the area of biochemical modeling.

Biochemical engineers offer a unique approach to biotechnology by modeling the biological phenomena of cells. These range from simple, non-interacting bacterial cells to complex tissues where individual cells are able to communicate with each other. A fundamental problem is the particulate nature of such systems, as cells normally occur in populations. A rigorous modeling approach is difficult because such models become mathematically and computationally challenging. In addition, biological details are only partially known at the molecular level-although remarkable advances have been made in recent years.

The goal of the workshop was to reevaluate the role of mathematical modeling in biochemical engineering. Compared to other advances in biotechnology, it may appear that mathematical modeling has played a somewhat minor role. The workshop was, therefore, useful in sensitizing the research community to modeling issues. Furthermore, the discussions helped in firming up the foundation for biochemical engineering by delineating the creative role modeling can play in biotechnology.

About 35 scientists and engineers from the United States, Europe, and Japan were invited to participate in this workshop. The four sessions were held over a two-day period. Each session consisted of four speakers who gave brief overview presentations on a broad topic. These served as the basis for extensive discussion periods following the presentations in each session.

The first session of the conference was devoted to the identification and analysis of parameters characterizing biological systems that are used in modeling. Jim Broach of the Department of Molecular Biology at Princeton University opened by giving an overview of the molecular mechanism used by cells in sensing their environment. His talk was followed by Mike Shuler of the Chemical Engineering Department at Cornell University. Mike discussed the Cornell single-cell model he developed and refined over the past decade. Mike Domach from Carnegie Mellon University then presented some of his work using improved NMR techniques to probe for activities in viable cell populations. Friedrich Srienc from the Department of Chemical Engineering & Materials Science and the Bioprocess Technology Institute of the University at Minnesota followed by describing advanced cytometric techniques that allow identification of parameters used in population balance models.

The second session was devoted to corpuscular models which most accurately describe the behavior of cell populations. John Tyson from the Biology Department of the Virginia Polytechnic Institute gave an overview on modeling of the cell cycle and its control mechanisms. He described the status of growth models on the basis of current knowledge of the molecular biology of the eukaryotic cell cycle. He also described the difficulties in extending a single cell model to a population model. Lorenzo Cazzador from the University of Padua, Italy, gave an overview of cell cycle models as they are used in biochemical engineering. John Villadsen from the Biotechnology Institute at the Technical University of Denmark spoke about population balance models and whether they are truly needed in view of the difficulties in using them. Data for the use of such models typically are difficult to obtain and the solutions are computationally intensive. The session was concluded by Doraiswami Ramkrishna from the Department of Chemical Engineering at Purdue University who introduced his recently developed self similarity theory for identifying population balance models from a wider range of multivariate population data.

The second day opened with a session on metabolic models. Greg Stephanopoulos from the Chemical Engineering Department at Masschusetts Institute of Technology gave an overview of some of their work on analyzing complex pathways. Jim Liao from the Chemical Engineering Department at Texas A & M University gave a talk on how stoichiometric relationships can be used in combination with metabolic control theory to predict improved pathway designs. Jay Bailey from the Biotechnology Institute at the ETH Zurich, Switzerland, gave a presentation on metabolic modeling and how the description of the intracellular reaction network is affected by the expanding volume of growing cells. Dhinakar Kompala, Department of Chemical Engineering at the University of Colorado at Boulder concluded by describing the application of a cybernetic modeling concept that incorporates a dynamic allocation of resources. The model is able to describe sustained oscillations observed in growing yeast cell populations.

The last session of the meeting was devoted to the most complex problem-the modeling of cell tissue. Since comparatively little is known of the handling of cell tissue systems, this session was the most open ended one. Dennis Bray from the Department of Zoology at the University of Cambridge, England, opened by offering insight into how cells might process transmembrane signals. Doug Lauffenburger from the Chemical Engineering Department at Masschusetts Institute of Technology spoke about how cell receptors lead to cell movement. Bernhard Palsson from the Bioengineering Department of the University of California at San Diego presented a talk on the way in which modeling and engineering concepts contribute to designing cell culture devices and how modeling can help in designing strategies for gene therapy. The session was concluded with a presentation by Wei-Shou Hu, Department of Chemical Engineering & Materials Science at the University of Minnesota, on modeling the development of complex tissues such as embryos of plants.

It appeared most natural and appropriate that the conference was held in honor of A.G. Fredrickson of the University of Minnesota, as he made significant contributions in all areas discussed at the Conference. Professor Fredrickson has made pioneering contributions on each of the session topics during the course of his past work. The conference concluded with a banquet in Fredrickson's honor, where an exhibition of a collection of his absorbing photographs titled "Nature and Man-Made Nature," uniquely framed the evening.

This innovative workshop was made possible by a grant from the National Science Foundation and by additional support from the Supercomputer Institute, the Department of Chemical Engineering & Materials Science, and the Bioprocess Technology Institute at the University of Minnesota. The Conference was co-chaired by Doraiswami Ramkrishna, Department of Chemical Engineering, Purdue University and Friedrich Srienc, Department Chemical Engineering & Materials Science and the Bioprocess Technology Institute at the University of Minnesota. They were assisted in the organization by Mike Flickinger, Department of Biochemistry and the Bioprocess Technology Institute, and by Robert Tranquillo and Wei-Shou Hu of the Department of Chemical Engineering & Materials Science at the University of Minnesota.

In This Issue:

International Conference on Parallel Computing

Positron Emission Tomography

Workshop on Modeling in Biochemical Engineering

Evolutionary Algorithms Workshop

Upcoming Workshop on Rational Drug Design

Seminar Synopses

Research Reports