MAJOR RESEARCH EFFORTS

Overview of Cellular Engineering Research at Rice University 
Cellular engineering has been defined as "Application of the principles and methods of engineering to problems in cell and molecular biology of both a basic and applied nature" and as "the purposeful modification of cell properties.”  Rapid progress in this area has been stimulated by advances in genomics and will require significant cooperation between scientists and engineers and will be greatly facilitated by the development of new interdisciplinary training programs.  To meet this challenge, our interdisciplinary summer REU in Cellular Engineering program focuses on metabolic and tissue engineering.  Metabolic engineering includes flux analysis, pathway regulation and control, and engineering of primary and secondary metabolites.  Emphasis areas for tissue engineering include cell signaling and response in movement, biomimetics, and analysis and manipulation of factors important in blood flow and hard and soft tissue formation.  These areas have direct biomedical applications in engineering improved practices for treatment of vascular and joint diseases.  Overviews of four examples of proposed interdisciplinary research groups in these areas are briefly outlined below and then each is described in more detail.  Each of the research themes has investigators from both biosciences and bioengineering, demonstrating the significant cross-disciplinary interactions within the Institute of Biosciences and Bioengineering at Rice. Our NSF REU grant is spurring development of new collaborations between bioengineers and bioscientists and providing training of a new type of researcher qualified to work at the interface of engineering and biology. 

Engineering of Hard and Soft Tissue Formation
This effort studies the effects of mechanical loading on tissue formation and remodeling at the cellular and tissue levels using three-dimensional mechanical and numerical models. It also investigates the expression of genes which encode extracellular matrix proteins, secretion of cytokines and growth factors related to tissue formation and resorption, and synthesis of collagenous matrix and mineralization in response to mechanical forces. In addition, complex computer analyses of the three dimensional architecture of hard and soft tissues, taken from different anatomical sites, is performed to further investigate the structural efficacy of tissue micro-architecture based on mechanical load. Understanding tissue behavior with respect to mechanical stimuli promises insight into developing cures and prevention schemes against excessive tissue resorption and demineralization with exposure to long-term bed rest, and possibly natural diseases such as osteoporosis and osteoarthritis. The group also investigates the use of polymer scaffolds for the development of tissue-engineered bone and cartilage (meniscus). This collaborative effort in tissue engineering is a powerful combination of the unique knowledge and experience of each group giving prospective students exposure to several research areas at the same time.

Cardiovascular Tissue Engineering
Several groups within bioengineering and biochemistry & cell biology are involved in projects dealing with engineering of tissues within the vascular system.  Projects in this area include the development of synthetic blood substitutes, the development of tissue engineered vascular grafts, the design of biomimetic scaffold materials, gene therapy approaches in vascular tissue engineering, and investigation of the effects of mechanical stimuli on vascular cell behavior.  These projects all have received extensive extramural funding and involve students from both engineering and basic science backgrounds working in an interdisciplinary environment, which broadly covers engineering approaches from the molecular level of protein engineering to the tissue and organ levels of complexity.

Engineering Cell Surface Interactions Regulating Movement
Researchers in this area study cell processes related to cell-cell interactions, particularly those involved in cell movement or adhesion.

Research areas include: the examination of signal-transduction of cell-cell interactions involved in pathogenic responses such as phagocytosis by gene array expression analysis; studies of calcium ion regulation of cell responses including its role in cell structure and movement via actin-myosin interactions; the molecular mechanisms of morphogenetic cell movements in developing embryos;  and the analysis of the ability of specific regulatory proteins to signal aggregation or affect adhesion.  The work involves not only cell biology approaches but also includes measurement of cell-cell forces and computer modeling of cell movement and regulatory processes.  The scope extends from studies of whole cell responses to the modeling of the dynamics of key protein components of motility and should provide students with a broad perspective on experimental and theoretical approaches in this important area of tissue engineering.

Metabolic Engineering
Technological advances for genetically engineering organisms using the vast amount of genomic sequence information available and improvements in experimental measurement and theoretical analysis of metabolic fluxes have facilitated production of high value-added products.  Recent interest in producing chemicals by biological processes through, so called "green chemistry" has gained corporate attention.  Although the microbial production of amino acids, vitamins, and antibiotics is well known, exciting applications of metabolic engineering to plants are now becoming commercialized. The following four important areas in metabolic engineering are addressed by projects among REU faculty.  Pathway development concerns the addition or modification of genes so the organism can form or degrade a new molecule not naturally associated with the organism; enzyme engineering takes advantage of advances in genetic technology to develop improved proteins of biotechnological importance through design or directed evolution; pathway engineering seeks to improve the metabolic flux to desired products of characterized metabolic pathways (among those of particular interest are those forming terpenes, indole alkaloids, and solvents); metabolic flux analysis and modeling can give a more quantitative picture of the limitations to pathway productivity and suggest strategies for genetic enhancement, and when this mathematical approach is coupled with the large data sets available from gene array expression profiles, improved methods for monitoring and predicting optimal  conditions for production can be developed.

Each of these projects involves integration of basic biochemistry and molecular and cell biology with bioengineering quantitative analysis and systems approaches to generalize the scientific findings and to allow development of real applications.  This type of team approach to biological problems is characteristic of what is currently being implemented in many biotechnology companies today.  It requires a new kind of person who, while an expert in only one field, feels scientifically comfortable in planning, discussions and analysis with all members of the project team.  The specific research components of our REU training program have been chosen with this goal in mind.  The variety of problems allows students to be familiar with many areas of cellular engineering.