Director's Message

In December 2002 the Department successfully moved into the new building. The move of all laboratories went right on schedule and I would like to thank Loretta Smith, Beth Maples, and Douglas Gurevitch for the excellent coordination and organization of this complicated process.

It is my pleasure to present our new Industrial Affiliate Program member, Genomatica. Dr. Christophe Schilling is the company's representative at the WIBE Industrial Advisory Board.

In this issue, we are featuring a new faculty member in the Department of Bioengineering, Dr. Xiaohua Huang. Dr. Huang received his Ph.D. degree from Stanford University and worked as a postdoctoral research fellow in the Department of Genetics at Harvard Medical School under the direction of Prof. George M. Church. Dr. Huang's expertise in genomics and systems biology will enhance the Department's activities in these areas.

The 2nd La Jolla Conference on Glucose Monitoring and Control that took place on February 13 -15 was a successful and fruitful event. In this issue, Dr. David Gough, who organized the conference, is sharing his thoughts about he conference and its future.

It gives me great pleasure to congratulate our Industrial Affiliate Program member, InnerCool therapies on winning the FDA approval on cathether cooling.

I would like to announce the 17th Annual Bioengineering Graduate Student Symposium, which will be held on March 8, 2003. This is an excellent opportunity for interested members of the academic and industrial communities and prospective students to learn about the current research projects in the Department.

The 4th UC System-wide Symposium on Bioengineering will be held on the UCSD campus on June 22-23, 2003. The previous meetings at UC Davis 2000, UC Santa Barbara 2001, and UC Berkeley 2002 made this symposium a tradition. Its purpose is to foster exchange and discussion on bioengineering research performed on the campuses of the University of California.

Our congratulations to Professor Jeff Hasty for being awarded a Sloan Foundation Fellowship, Dr. Albert Chen and Professor Bob Sah for winning American Academy of Orthopaedic Surgeons poster prize, Dirk Albrecht for winning the Grand Prize for posters at the 2003 Jacobs School of Engineering Research Review, and Bioengineering premedical student Yosun Chang for receiving the National AP Scholar and AP Scholar with Distinction awards.

Dr. Shu Chien, Director

WIBE Industrial Affiliate: Genomatica
Back to beginning.

Genomatica, a privately-held systems biology company located in San Diego, CA, was co-founded in early 2000 by UCSD Bioengineering Professor Bernhard Palsson, Ph.D, a recognized leader in cellular modeling, and Christophe Schilling, Ph.D., a former graduate student of the Department of Bioengineering, who currently serves as Vice President and Chief Technical Officer. The Company is based on pioneering technology that enables the construction of predictive genome-scale models of metabolism. This technology allows biotech and pharmaceutical researchers to analyze, interpret and predict cellular behavior to increase the efficiency of biological discovery and systems biology research.

Genomatica's patent pending SimPheny™ modeling technology integrates vast amounts of diverse high-throughput biological data being generated by biopharmaceutical research, such as gene sequence, gene expression, proteomic, metabolomic and phenotypic data. This voluminous and rapidly emerging data is used to build virtual cells in silico. These in silico models are being used to transform the way drugs are discovered and organisms are engineered in the 21st Century. With an initial emphasis on microbial organisms, these in silico models are capable of generating improved designs for strain engineering to enhance fermentation-based bioprocesses, as well as generating antimicrobial targets and a systems level understanding of metabolism that can drive the antimicrobial drug discovery process.

Genomatica's business strategy is to commercially implement its in silico models through corporate partnerships and technology access agreements with academic and institutional researchers. To achieve this strategy the Company is applying SimPheny to develop models for various industrially relevant organisms and multiple human pathogens, as well as models for various human cell types and related disease conditions. The Company's initial technology focus is on modeling cellular metabolism, regulation and signal transduction, comprising fundamental processes that are very well characterized today. Genomatica's goal is to be the leading developer of biological modeling and simulation technologies to drive life sciences research.

Because the complexity of living cells is such that their behavior cannot be computed precisely, modern modeling approaches in systems biology will have to accommodate inherent biological uncertainty in addition to being data-driven, capable of integrating diverse biological data, experimentally validated in an iterative fashion, scalable to thousands of variables, and broadly applicable. Genomatica has developed SimPheny to meet these requirements. This proprietary computationally-based methodology to modeling cellular metabolism and regulation captures the physical and chemical constraints inherently placed on cells, which limit cellular behavior. SimPheny incorporates experimental data about individual components of organisms to derive highly accurate models of cellular systems centered around metabolism - the chemical engine that drives the living process and forms the basis for much of human disease. Genomatica's in silico modeling technology, SimPheny, can be used to accurately predict the cellular functions, behavior, fitness and performance characteristics of cells under changing environmental, physiological and genetic conditions.

Below is a screenshot from SimPheny.

Figure 1: Screenshot from the SimPheny™ Modeling Platform

Genomatica has currently established five microbial models of human pathogens and industrial organisms with applications in antimicrobial drug research and strain engineering. These models have advanced the Company's efforts to integrate high throughput experimental data and to model metabolic regulation and associated signal transduction pathways. The development of these models and technology as a whole are supported by extensive federal funding, which the company has received from the National Institutes of Health (NIH), National Science Foundation (NSF), Department of Defense (DOD), and the Department of Energy (DOE). This modeling technology was featured in the February 2001 issue of Nature Biotechnology and the August 2002 issue of the Journal of Bacteriology. Most recently, the technology was demonstrated in a paper titled "Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth," which appeared in the November 14, 2002 issue of Nature.

Genomatica has entered into academic collaborations with leading in silico and systems biology researchers at the University of Delaware, Penn State University, and the University of Massachusetts. Additionally, the company has entered into an industrial partnership with the Dow Chemical Company to develop an in silico model for use in microbial metabolism and bioprocess modeling.

For more information, please visit Genomatica's website at www.genomatica.com or contact us at info@genomatica.com.

Powell-Focht Bioengineering Hall Move

Back to beginning.

UCSD Bioengineering successfully moved into the new Powell-Focht Bioengineering Hall building in December 2002. It was a highly coordinated process that was made possible by the wonderful organization and preparation by Loretta Smith, Beth Maples, and Douglas Gurevitch. The Open House/Holiday Party on Thursday afternoon, December 19th, provided a chance for the Department to celebrate its new home, to appreciate its people for their great effort of making the move as smooth as possible, and to welcome friends and colleagues to the new building.

2nd La Jolla Conference on
Glucose Monitoring and Control

The incidence of diabetes is growing worldwide at an alarming rate. In many developing and industrialized nations the incidence has reached as high as 10%, including a large increase of diabetes in young people. This epidemic will place increasing demands on all health care resources. The Diabetes Complications and Control Trial completed in 1993 demonstrated scientifically that therapy resulting in a reduction in mean blood glucose levels can lead to a dramatic reduction in the complications of diabetes. Yet this important revelation has not been generally applied in the most effective manner because of the lack of acceptable means for close blood glucose management, which requires frequent glucose monitoring and an appropriate means and control strategy for delivery of medications.

A conference was held in La Jolla on February 13-15, 2003, to review the state-of-the-art. The intent was to convene a small group of 100 of the most influential leaders in the field from industry and academia, and provide a setting for technical presentations, open discussions and informal exchange. The conference focused on devices for glucose measurement and control strategies for medication delivery instead of approaches involving organ or islet transplantation, stem cells, or other biological components, as devices are closer to clinical introduction. There were presentations on new methods for tissue glucose sampling and measurement, short-term implantable sensors, long-term implanted sensors and internal telemetry, insulin pumping systems, architectures of blood glucose control systems, algorithms, and system performance targets. Results were presented from modeling studies, animal studies and human trials. There was considerable discussion and exchange, and the conference was widely considered to be a success. The proceedings will be published in the form of a book.

The conference was organized by David Gough under the ongoing Project on Glucose Monitoring and Control, which is part of the UCSD Whitaker Institute for Biomedical Engineering. There was support from industry, the Whitaker Institute, the Department of Bioengineering, and interested benefactors. With the nearing clinical introduction of these devices and the interest in optimizing their effectiveness, there will be a third meeting of this series next year.

David Gough

Announcements

San Diego Union Tribune announced on January 30, 2003 that InnerCool therapies, Inc. won the FDA approval on cathether cooling. The company has always had an ingenious approach with tremendous potential. Now this is validated by the rigorous process of review and approval by FDA. This is the recognition of the company's innovative idea, excellent research and development, superb due-diligence, and effective management that culminated in this success." We are proud that our IAB member (Dr. John Dobak) and our JSOE colleague (Professor Juan Lasheras) are having this great accomplishment through fruitful collaboration which is a model for us.

The U.S. News & World Report has selected the UCSD Jacobs School of Engineering to be featured in its upcoming Guide to Graduate Studies (to be published at the same time as the annual rankings in April 2003). JSOE is the only engineering school in the nation, and UCSD is the only West Coast school in any discipline to be featured! Therefore, this is a marvelous opportunity for us to be presented to the whole nation and beyond. Starting from January 17, the photographer, Ken Jarecke followed one graduate student from each JSOE department (Vicki Chin in our department) for a week, toured the Powell-Focht Bioengineering Hall and other buildings, and attended some classes and various events.

The Whitaker Institute has received $25,000 award from UCOP for the UC System-wide Biomedical Engineering Education Consortium. This is the first award issued to the Institute towards the Multi-Campus Research Unit project.

The Junior Science & Humanities Symposium (JSHS) is a national competition that recognizes extraordinary achievement in scientific research at the high school level. Students conduct an original research project, write a comprehensive research paper, and give a formal presentation to judges in a symposium format. The program is a showcase for some of the top science, math, and engineering high school students in the nation. The Southern California JSHS hosts students from the ten southern California counties. The competition will be held at UC Irvine on March 21-22, 2003.

The 17th Annual Bioengineering Graduate Student Symposium will be held on March 8, 2003. This event, sponsored by the Bioengineering Graduate Students at UCSD, offers an excellent opportunity for interested members of the academic and industrial communities, as well as prospective students, to learn about the current research projects in the Department. The Symposium will be held in Y.C. Fung Auditorium in the brand new Powell-Focht Bioengineering Hall, starting from 9 a.m. Talks will be presented which overview both current laboratory research and individual student thesis projects. Following the morning presentation, a poster session will allow attendees to explore projects in detail and interact with students and faculty. Complimentary breakfast and lunch will be provided.

The 4th UC System-wide Symposium on Bioengineering will be held on the UCSD campus on June 22-23, 2003. The previous meetings at UC Davis 2000, UC Santa Barbara 2001, and UC Berkeley 2002 made this a great tradition. The purpose of the symposium is to foster exchange and discussion on bioengineering research performed on the campuses of the University of California. The symposium will take place in the newly completed Powell-Focht Bioengineering Hall and in adjacent lecture halls on the UCSD campus. Details about this Symposium can be found on the website http://ucbmes.ucsd.edu/.

Second Annual California Tissue Engineering Meeting will be held on September 26 & 27, 2003 at University of California, San Diego. The purpose of California Tissue Engineering Meeting is to provide a forum for education and dissemination of research and development knowledge, for students and researchers in academics and industry, in the field of tissue engineering and regenerative medicine. The meetings are open to all interested investigators, with a particular focus on students and young investigators within the State of California. The meetings will allow students and researchers to gain new knowledge across the broad tissue engineering field and the related research and development areas. They will provide a forum for young investigators to present and discuss their own work. They will provide an environment that will encourage exchange of information and collaboration between individuals, groups, and between academia and industry.

The winter meeting of the Whitaker Institute Industrial Advisory Board took place on February 20, 2003. For the first time, it was held in Zweifach Library of the new Bioengineering building. Bioengineering new faculty Dr. Xiaohua Huang gave a talk on "Single Molecule Analysis and Integrated Bioanalytical Systems for Genome Research." The Board is working on organizing a West Coast Meeting on Regulatory Issues, which will be held sometime in November of 2003.

WIBE Profile: Xiaohua Huang

Back to beginning.

Dr. Xiaohua Huang joined the UCSD Department of Bioengineering in September 2002. He received his B.S. in Chemistry from Zhongshan University in China and his Ph.D. in Biophysical Chemistry from Stanford University. His graduate advisor was Prof. Steven G. Boxer. Following graduate school, he did postdoctoral work with Prof. David C Ward in the Departments of Genetics and Molecular Biochemistry and Biophysics at Yale University. Prior to his appointment in UCSD Bioengineering, Dr. Huang was a postdoctoral research fellow in the Department of Genetics at Harvard Medical School under the direction of Prof. George M. Church.

Dr. Huang is regarded as a key player in the arenas of genomics, systems biology and nano-biotechnology. Dr. Huang's appointment brings to UCSD Bioengineering expertise in genomics and systems biology and will greatly enhance our activities in these emerging interdisciplinary frontiers.

Dr. Huang's research is in the areas of genomics, systems biology and nano-biotechnology. He is particularly interested in developing the next generation of integrated bio-analytical systems, lab-on-a-chip and nano-technology based molecular devices. Developing experimental and computational tools to elucidate, model and engineer genetic regulatory networks is another area of his research interest.

The revolution in modern biology is largely due to the development of novel physicochemical and engineering methods to carry out high throughput assaying and measurements of genes and proteins. Automated DNA sequencing, polymerase chain reaction (PCR) and gene expression profiling using microarrays, to name a few, have fundamentally changed the landscape of biology and biomedical research. However, existing analytical technologies remain inadequate for many genome and proteome-scale studies due to the enormous size and complexity of many biological systems. For example, current costs associated with large-scale sequencing (estimated to be tens to hundreds of millions of dollars per mammalian genome) remain a central limiting factor for genome sequencing efforts. It is clear now that a paradigm shift in terms of methodology, scale and engineering is needed to develop more powerful enabling technologies for systems studies. One of Dr. Huang major research focus is to develop innovative integrated bioanalytical systems for ultra fast whole genome DNA sequencing, pharmacogenomics, molecular diagnostics and digital gene expression profiling. His strategy is to focus on massive parallelization, miniaturization and systems integration of biochemical reactions and detections.

Amplification of DNA by PCR is used universally to make large number of copies of DNA, a capability that has led to revolutionary advances. Dr. Huang is the pioneer of one similar high throughput technology. A novel and powerful technology for amplification called the rolling circle amplification (RCA) was recently developed by Dr. Huang and his colleagues. His recently work in Prof. Church laboratory has demonstrated the feasibility of massively parallel separation and isothermal amplification cloning of single DNA molecules on solid surfaces using RCA. Tens to hundreds of millions of single DNA molecules can be separated and cloned in situ on the functionalized surface of a glass microscopy slide. Each molecular clone on the surface can serve as an addressable nano-reactor or nano-sensor for DNA sequencing, and other biochemical reactions and detections. He has also invented a novel DNA sequencing technology. His future research will involve further development of these technologies and engineer automated integrated systems for whole genome sequencing, digital gene expression profiling and molecule diagnostics.

Another area of Dr. Huang' research concerns genetic regulatory networks. Complex genetic regulatory networks orchestrate the spatial and temporal expression of genes in response to intra- and extra-cellular signals to give rise to different cell types and tissues, stress response and other myriad of functions. Regulated expression of most genes begins with the sequence specific binding of transcription factors to the regulatory sequences of the gene. Identifying the components, structures and organizations of these networks is the first essential step towards an integrated and predictive understanding of cell cycle control, differentiation and apoptosis. Despite the availability of genome sequences of many organisms including human and mouse, the regulatory sequences of most of their gene remain unknown. Dr. Huang and his former colleagues Prof. Martha Bulyk and Prof. George Church at Harvard Medical School have developed a high throughput microarray technology to characterize DNA binding specificities of transcription factors.

This work has demonstrated that DNA microarrays can be used to accurately measure the protein-DNA binding affinity, DNA sequence binding specificities of transcription factors and therefore the feasibility of using DNA microarrays to identify putative binding sites of transcription factors in vitro on a genome scale. Dr. Huang future research in this area is to develop high throughput experimental and bioinformatics tools to identify the network components and to deconvolute, reconstruct and model these complex genetic regulatory networks. The systematic elucidation of these networks will help us better understand and interfere with cellular development and disease processes, and may lead to better tissue and organism engineering.

Image of rolling circle amplification (RCA) products from single DNA molecules on a glass surface.
Oligonucleotide primers for the amplification were tethered onto the glass surface. Equal numbers
of two different circular DNA molecules were separated and amplified on the surface. The amplified
products were detected with fluorescent probes. Each spot contains the amplified products
from an individual circular DNA molecule.

In the area of nano-biotechnology, Dr. Huang's future research will involve developing nano-materials for in vivo and in vitro imaging and detection of biomolecules. In addition to his experimental qualifications and abilities, Dr. Huang is computationally adept and is a paradigm researcher in the new systems biology and bioinformatics arena.

We are happy to welcome Professor Huang in UCSD Bioengineering!

Bioengineering Seminar Schedule

Spring Quarter 2002
Room 2111 Warren Lecture Hall
2:30 - 3:30 P.M. Fridays
BE 281 and The Whitaker Institute of Biomedical Engineering

WIBE Faculty Honors

Professor Jeff Hasty received the prestigious Sloan Foundation Fellowship from the Alfred P, Sloan Foundation in February 2003.

Dr. Albert Chen and Professor Robert Sah and their collaborators from Rush Medical College presented a poster "Biomechanical Properties of Tissue Engineered Cartilage from Adult Human Chondrocytes" that was awarded 1st place overall at the 70th Annual Meeting of the American Academy of Orthopaedic Surgeons in New Orleans, LA (February 5-9, 2003).

Student Honors

At the JSOE Engineering Review, 18 Bioengineering graduate students submitted excellent posters. Dirk Albrecht's poster (faculty advisors Professors Sangeeta Bhatia and Robert Sah) on "Dielectrophoretic Cell Patterning within Tissue Engineering Scaffolds" was awarded the Best Poster for the Department and the Grand Prize for the entire JSOE.

Yosun Chang, Bioengineering premedical student received the National AP Scholar and AP Scholar with Distinction awards. Each September, the College Board recognizes the many high school students who have distinguished themselves academically by announcing AP award recipients. There are several types of awards, granted for various levels of achievement. Although these are not monetary awards, the students receive a certificate and their achievement is acknowledged on any subsequent AP Grade Reports sent to colleges. Award recipients not only gain recognition from colleges, but also win the admiration of their peers, families, and communities. You can read further on the awards at: http://www.collegeboard.com/ap/students/benefits/awards.html.

New Bioengineering Ph.D.'s and Their Thesis Titles

Carlos Vera, "Junctional Complex: Molecular Architecture and Contributions to Erythrocyte Membrane Biomechanics". Carlos passed his Ph.D. examination on August 27, 2002 and is now working as a Postdoctoral Fellow in the Department of Bioengineering, UCSD

Congratulations to all!

University of California, San Diego
Whitaker Institute of Biomedical Engineering
9500 Gilman Drive
La Jolla, CA 92093-0427

(858) 822-2290