George Georgiou Sang Yup Lee This issue of Biotechnology Journal is dedicated to Professor Michael Shuler of Cornell University in honor of his seminal research contributions and his pivotal role in the establishment and growth of Biochemical Engineering. After 38 years of service to Cornell University where he started his career in January 1974, Mike announced his impending phase retirement, beginning in 2012. The organizers of the Biochemical and Biomolecular Engineering XVII conference held in Seattle on June 26–30, 2011, Professors François Baneyx, Costas Maranas and Dr. Beth Junker, together with one of us, organized a session on “Biomolecular Networks” in honor of Mike. This was the first time in the 30-year history of the Biochemical and Biomolecular Engineering conference series, widely regarded as the most influential meeting in the field, that an individual had been recognized for his life-long impact and contributions. Almost 30 years ago, Mike's vision led to the development of the first deterministic and chemically accurate mathematical model of an organism, one that could predict the growth rate, cell size and macromolecular content (total RNA, DNA and protein) of Escherichia coli [1]. The model, known as the Cornell model, employed a set of differential equations that could account for key metabolic processes (e.g. ATP generation, total RNA synthesis, DNA replication, initiation of cell division, etc.) based on available biochemical information. The model even accounted (though implicitly) for events such as noise in gene expression and its effect on asynchrony in cell division and on population dynamics. These concepts were way ahead of their time. Over the years, Mike and his students refined the single cell bacterial model by adding further mechanistic detail in amino acid biosynthesis, protein translation, fermentative metabolism, and others (see [2-4] for some representative publications). This amazing modeling effort represents one of the most significant contributions to quantitative biology to this day. ... Mike's vision led to the development of the first deterministic and chemically accurate mathematical model of an organism ... In addition to his modeling work, Mike has pursued a breathtaking array of different research projects. He is widely acknowledged as the first engineer to focus on large-scale plant tissue culture for the production of complex secondary metabolites such as taxol [5]. This process enabled the mass production of this powerful chemotherapeutic agent. His group worked for many years on protein expression in host systems ranging from E.coli to mammalian cells. Some of his major accomplishments in this field include the co-development of the widely used “High five” insect cell line for high protein expression [6], and methods to increase the productivity of recombinant CHO cells in bioreactors [7]. His more recent “Body on a Chip” technology represents yet another example of his ingenuity [8]. Mike and his students used microfabrication techniques to build devices consisting of several compartments that are seeded with human cells from different organs and are interconnected via channels. Each compartment constitutes a simple tissue analog and using modeling and scale-down approaches, flow rates are adjusted to mimic fluxes across tissues in the human body. The “Body on a Chip” was one of the first meaningful experimental systems for determining drug pharmacokinetics and biodistribution in vitro and inspired numerous follow-up studies by other researchers. Mike's contributions and leadership in biochemical engineering education are equally impressive. His “Bioprocess Engineering” textbook [9] is widely used in introductory biochemical engineering courses throughout the world. He has worked tirelessly to promote the roles of chemical engineers in biological and biotechnological research. He played a pivotal role in the creation of the American Institute of Medical and Biological Engineers (AIMBE) and was the founding editor of Biotechnology Progress, published by ACS. At Cornell, Mike served as chairman of the Chemical Engineering Department and, seven years ago, he founded the Biomedical Engineering Department, which has already risen to international prominence within only 7 years. Finally, Mike has been the mentor of well over 80 Ph.D., M. Eng, and post-doctoral students who have gone on to highly successful careers in academia and industry. He is legendary for his superb mentorship and his dedication to the welfare of his students. Mike is legendary for his superb mentorship and his dedication to the welfare of his students. We are very grateful to Biotechnology Journal for its offer to dedicate this Special issue to Mike Shuler. Mike is so well liked and so many of us in the community are indebted to him for his help and mentorship over the years, we could have easily filled not one but many, issues with contributions in his honor. Given the understandable space limitations, we embarked on a more modest project - soliciting manuscripts from the three invited speakers that participated in the “Biomolecular Networks” symposium from the Biomolecular Engineering XVII conference (Professors Doug Lauffenburger at MIT [10], Sang Yup Lee at KAIST [11] and James C. Liao at UCLA [12]), from Mike's current and former bioengineering colleagues at Cornell (Professors Douglas S. Clark [13], now at UC Berkeley, Daniel A Hammer [14], now at U. Penn, Mark W. Saltzman [15], now at Yale, Kelvin Lee [16], now at U. Delaware and Matt P. DeLisa [17] at Cornell) and from several of his former students holding academic positions (Professors Michael M. Domach at CMU, Mohammad Ataai at U. Pittsburgh [18], Susan C. Roberts at U. Massachusetts [19], William E. Bentley at U. Maryland [20], Byung-Gee Kim at Seoul Ntl U. [21]). Everyone invited to participate agreed to do so with great enthusiasm. The articles in this issue reflect how the seeds planted by Mike in the 70s and early 80s have blossomed to encompass a wide gamut of topics that constitute the backbone of the modern biochemical engineering enterprise. They include the modeling of signal transduction, trafficking and metabolic processes for applications ranging from drug target discovery to tissue reconstruction, metabolic engineering and bioprocess optimization; novel in vitro tissue models for pharmacology and toxicology research; biomolecular engineering systems for protein engineering and bioactive peptide discovery; and advanced technologies ranging from the production of secondary metabolites by tissue culture to the development of complex biological systems and devices. It is not hard to glean how the concepts and research directions Mike pioneered have provided the intellectual impetus for the papers in this issue. The articles reflect how the seeds planted by Mike have blossomed to constitute the backbone of the modern biochemical engineering enterprise. In closing, we would like to thank the authors for putting together this exciting volume and deserving tribute to Mike. Last but not least, we are grateful to the superb editorial staff of Biotechnology Journal who were instrumental in ensuring that the editorial process was completed smoothly and rapidly, and to the external reviewers that provided invaluable feedback to the contributors and the editors. Sincerely, Prof. George Georgiou Department of Biomedical Engineering, The University of Texas at Austin, USA Prof. Sang Yup Lee Co-Editor-in-Chief, Biotechnology Journal

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