Biotechnology Training Retreat

Fifteenth Annual

Saturday, April 8, 2006

Christian Brothers Retreat & Conference Center Napa, CA

Fifteenth Annual Biotechnology Training Retreat

Saturday, April 8, 2006

Christian Brothers Retreat & Conference Center Napa, CA

Co-sponsored by:

NIH Training Program in Biomolecular Technology (NIH-1-T32-GM08799)

UC Davis Designated Emphasis in Biotechnology Graduate Program (DEB)

UC Davis Biotechnology Program

Table of Contents

Welcome 2 NIH Training Program in Biomolecular Technology 3 Designated Emphasis in Biotechnology, UC Davis 4 UC Davis Biotechnology Program 5 Retreat Agenda 6 2006 Poster Titles 7 Oral Presentations 9 Bioethics 25 Poster Abstracts 27 Company Affiliates 36 Training Retreat Participants 2006 46 Mission of UC Davis Biotechnology Program 51 NIH Training Grant Information 52 NIH Training Grant Faculty 53 NIH Training Program in Biomolecular Technology 55 Goals and Mission of Designated Emphasis in Biotechnology Progam 56 DEB Program Students as of March 2006 60 DEB Faculty Participants 63 The Value of Internships 66

Welcome

On behalf of the UC Davis Biotechnology Program, the executive committees of the Designated Emphasis in Biotechnology (DEB) and the NIH Training Grant in Biomolecular Technology, we thank you for joining us as we honor our 2005-06 fellows and their preceptors, as well as our industry affiliates. We plan to have a day filled withgreat science, beautiful scenery and delicious food and wine. The logistics of this retreat has been graciously overseen by our assistant director, Carey Kopay and new event manager, Marianne Hunter. Please welcome our Biotechnology Fellows. Our 5 NIH Fellows include: Suzanne (Balko) Barber, Chemical Engineering major (preceptor is Tonya Kuhl); Allison Dickey, Chemical Engineering major (preceptor is Roland Faller); Corey Dodge, Chemical Engineering major (preceptor is Karen McDonald); Gian Oddone, Chemical Engineering major (preceptor is David Block) and Jennifer Warren, Civil and Environmental Engineering major (preceptor is Stefan Wuertz). Our 4 Biotechnology Fellows (industry and campus fellowships) include: Laura Higgins, Molecular, Cellular & Integrative Physiology major (preceptor is John “Jack” Rutledge); Vannarith “Van” Leang, Chemical Engineering major (preceptor is Robert “Bob” Powell); Riccardo LoCascio, Microbiology major (preceptor is David Mills) and Vu Bao Trinh, Biochemistry & Molecular Biology major (preceptor is Yohei Yokobayashi). We will be selecting our 2005-06 fellows in late May. Fellowship nominations are due on Monday, May 8, 2006. Forms are on the web at www.deb.ucdavis.edu). We would also like to recognize our First Year Biotechnology Fellows: Domink Green (Biochemistry and Molecular Biology); Connie Jen (Biochemistry and Molecular Biology) and Barbara Nellis (Chemical Engineering). Dominik and Connie have already become members of the DEB. Due to the limited time for oral presentations, we will showcase research performed by other students in the DEB program in the poster session. Please congratulate all of these outstanding predoctoral candidates. We are very proud of all of them. We are completing our fourth year of the NIH Biotech Training Grant and are busy assembling our competitive renewal proposal, which is due this May. We hope to double the number of fellows supported. We need letters of support from our industry partners. As a reminder, the DEB graduate program is the formal training program for the NIH training grant and the number of DEB students is currently up to 86. Each of our students is showcased on the newly revised DEB website (www.deb.ucdavis.edu). In regard to industrial internships for 2006, we are busy placing students. Aminah Ikner started her internship at Novozymes in March, Li Peng and Anh Phung are interviewing with Genentech and many more are in the application process at Amgen, Monsanto-Calgene, Agilent, Pioneer Hibred and Scios. We would like to thank all of our industry affiliates for their support of our training program. Hopefully, we can find a match for all of the students. A number of students graduated in 2005-6 with their PhDs plus a DEB: Susanne Berglund; Amanda Ellsmore Fischer; Ze He; Jien-Ren “Jerry” Ku; Ryann Muir; Sheetal Singh; Bob Ward and Jennifer Weidhaas. Please see the winter edition of Biotechnology Times for more information.

Please Come Again on March 31, 2007 (tentative date).

With warm regards,

Judy Kjelstrom, Director, UC Davis Biotechnology Program

NIH Training Program in Biomolecular Technology

(NIH-1-T32-GM08799)

Bruce D. Hammock, Director Karen McDonald, Co-Director Martina Newell-McGloughlin, Co-Director

Executive Committee

Faculty: George Bruening (Plant Pathology) Dan Gusfield (Computer Science) Ian Kennedy (Mechanical & Aeronautical Engineering) J. Clark Lagarias (Biochemistry & Molecular Biology) Kit Lam (MED: Internal Medicine (Hemotology/Oncology) John Yoder (Plant Sciences)

Industry: Kenneth Gruys, Monsanto, Calgene campus Joel Cherry, Novozymes, Inc. Linda Higgins, Scios

Judith A. Kjelstrom, Program Coordinator (Ex-Officio Member)

Designated Emphasis in Biotechnology (DEB) Graduate Program

www.deb.ucdavis.edu

Executive Committee

Abhaya Dandekar, Chair David Rocke Karen McDonald Robert Rice (Term ends 6/30/06) Katayoon “Katie” Dehesh (Term starts 7/1/06) Susanne Berglund, Student Member (Term ended 3/31/06) Kou-San Ju, Student Member (Term starts 4/06)

Judith A. Kjelstrom Program Coordinator (Ex-Officio Member)

UC Davis Biotechnology Program www.biotech.ucdavis.edu

Judith A. Kjelstrom, Ph.D., Director Carey Kopay, Assistant Director

Cathy Miller, Budget Analyst Marianne Hunter, Event Manager

One Shields Ave 301 Life Sciences Davis, CA 95616 [email protected] (530) 752-3260 Fax: (530) 752-4125

5 UC Davis Fifteenth Annual Biotechnology Training Retreat April 8, 2006 Christian Brothers Retreat & Conference Center

6:45 am – Bus departs Davis, Parking Lot #41 (Rebecca Parales, Jason Eiserich)

8:00 – 8:30 am Registration/Continental Breakfast 8:30 – 8:45 am Welcome Bruce Hammock Director, NIH Training Grant in Biomolecular Technology Morning Session Chair Martina Newell McGloughlin Co-Director, NIH Training Grant in Biomolecular Technology 8:45 – 10:20 am Presentations 8:45 am Gian Oddone Mentor: David Block 9:10 am Jill Deikman Monsanto, Calgene Campus 9:35 am Allison Dickey Mentor: Roland Faller 10:00 am Corey Dodge Mentor: Karen McDonald 10:20 – 10:50 am Break / Poster Viewing 10:50 am – 12:20 pm Presentations 10:50 am Aaron Nguyen Scios, Inc. 11:15 am Suzanne Balko Mentor: Tonya Kuhl 11:35 am Jennifer Warren Mentor: Stefan Wuertz 12:00 pm Martina Newell- Bioethics Question (Handout) McGloughlin 12:20 – 2:15 pm Lunch / Poster Viewing Afternoon Session Chair Karen McDonald Co-Director, NIH Training Grant in Biomolecular Technology, DEB Executive Committee 2:15 – 4:00 pm Presentations 2:15 pm Martina Newell- Bioethics Question (Discussion) McGloughlin Chiron Corp. 2:40 pm Indresh Srivastava Mentor:John (Jack) Rutledge 3:05 pm Laura Higgins Novozymes, Inc. 3:30 pm Aubrey Jones Mentor: David Mills 3:55 pm Riccardo LoCascio 4:15 pm Short Break (10 min) 4:25 – 6:00 pm Presentations 4:25 pm Vu Bao Trinh Mentor: Yohei Yokobayashi 4:50 pm Douglas Banks Amgen Inc. 5:15 pm Vannarith Leang Mentor: Robert Powell 5:40pm TBA Genentech 6:15 pm Closing Remarks Bruce Hammock / Martina Newell McGloughlin 6:30 pm – Bus departs Napa

6 2006 Poster Titles

A. “Homing Site Requirements of the Lactococcal Goup II Intron In Its Native Host” David A. Sela*, Helen Rawsthorne, and David A. Mills Department of Viticulture and Enology, University of California, Davis, CA 95616

B. “Engineering Oilseed Crop Nutrition” Henry E. Valentin1, Balasulojini Karunanandaa2, Qungang Qi2, Alison Van Eenennaam1, Eric Aasen1, Charlene Levering1, Christine Shewmaker1, Susan Norris2, Kim Lincoln2, Rob Last2, Ming Hao2,Susan Baszis2, Pamela Jensen2, Yun-Hua Wong2, JianJiang2, Farhad Moshiri2, Aundrea Warren2, Mylavarapu Venkatramesh3, Kenneth J. Gruys1.Jennifer Gonzales, AJ Nava, Janet Nelsen, Jeff Haas, Virginia Ursin 1 Monsanto Company, Calgene Campus 2 Monsanto Company 3 Renessen LLC

C. “Lipolysis products alter protein and lipid structural characteristics in the plasma membranes of human monocytes” Laura J Higgins1*, Nabil M Saad2, Oliver Fiehn2, John C Rutledge1 1Dept of Internal Medicine, 2Genome Center, University of California, Davis, 95616

D. “Immunophenotyping of Leukocytes on Antibody Microarrays” He Zhu*, Kazuhiko Sekine, Mehmet Toner, and Alexander Revzin Section of Microbiology, University of California, Davis, CA, 95616

E. “High Affinity High Specificity Alpha4 Beta1 Integrin Targeting Peptides for Lymphoid Cancers” Li Peng*, Ruiwu Liu, Jan Marik, Xiaobing Wang, Yoshikazu Takada, Kit S. Lam Department of Internal Medicine, UC Davis Cancer Center, University of California Davis, 4501 X Street, Sacramento, California 95817

F. “α-Tubulin Detyrosination: A Molecular Switch for Regulating Vascular Smooth Muscle Cell Proliferation” Anh D. Phung1*, Karel Souček1, Lukáš Kubala1, Richart W. Harper1, J. Chloë Bulinski4,5 & Jason P. Eiserich1, 2, 3 1Department of Internal Medicine, 2Department of Physiology and Membrane Biology, and 3Cancer Center, University of California, Davis, California 95616 USA. 4Department of Biological Sciences and 5Department of Pathology & Cell Biology, Columbia University, New York, NY 10027, USA.

G. “Novel Biofunctional Core/Shell Quantum Dots for Multimodality Imaging” Heather A. Palko1+, Zane S. Starkewolfe1*+, Shizhong Wang1,3, Li Peng2*, Kit S. Lam2, Angelique Y. Louie3 1Department of Chemistry, University of California, Davis, CA 95616 2Divison of Hematology and Oncology, Department of Internal Medicine, University of California, Davis, CA 95616 3Department of Biomedical Engineering, Chemistry Graduate Group, University of California, Davis, CA 95616 + These authors contributed equally to this work

H. Engineering Oilseed Crop Nutrition Henry E. Valentin1, Balasulojini Karunanandaa2, Qungang Qi2, Alison Van Eenennaam1, Eric Aasen1, Charlene Levering1, Christine Shewmaker1, Susan Norris2, Kim Lincoln2, Rob Last2, Ming Hao2,Susan Baszis2, Pamela Jensen2, Yun-Hua Wong2, JianJiang2, Farhad Moshiri2, Aundrea Warren2, Mylavarapu Venkatramesh3, Kenneth J. Gruys1 1 Monsanto Company, Calgene Campus. 2 Monsanto Company 3 Renessen LLC

See pages 27 - 35 for poster abstracts.

*Member of DEB graduate group

Oral Presentation Abstracts

9 NIH FELLOW: Gian Oddone

A METABOLIC MODELING APPROACH TO OPTIMIZING RECOMBINANT PROTEIN PRODUCTION IN L. LACTIS FERMENTATIONS

Presenter: Gian Oddone* Authors: Gian M. Oddone and David E. Block Affiliations: Departments of Chemical Engineering & Material Science1 and Viticulture & Enology2, University of California | One Shields Ave | Davis, CA 95616 Preceptor: David Block

Lactococcus lactis, a species of Lactic Acid Bacteria (LAB), continues to show great promise for use as a vaccine delivery vehicle thanks to its widespread use in the dairy industry, GRAS status, genome sequence availability, resistance to degradation in the GI tract, and susceptibility to food grade tools for genetic modification. Even so, there remain challenges in bringing this biomedical application to fruition, specifically with respect to currently attainable levels of recombinant protein expression in cultures of LAB. Recent work submitted for publication has optimized bioreactor conditions for recombinant protein expression in L. lactis IL1403. Under optimal bioreactor conditions, levels of GFP, a model recombinant protein, can be increased 50% per cell and 8-fold in bulk concentration over levels obtained under standard laboratory conditions.

The current research aims to further increase expression through the use of genetic modification of the bacterial strain. Response surface methods, while proving to be very useful in optimizing bioreactor conditions, cannot be used to optimize genetic configuration of the host strain because genetic modifications cannot be dialed in so easily as, for example, a new temperature set point. Therefore, metabolic modeling is required to study the potential impact of plausible genetic modifications. Metabolic flux analysis (MFA) of a genome-scale L. lactis metabolic network leverages the vast available information on reaction stoichiometry to estimate the rates of all intracellular reactions, among them the reaction producing the recombinant protein. The desirability of a particular genetic modification can be estimated by using MFA to analyze the metabolic model that results from that modification. This procedure provides a basis to target particular genes for modification in progressing toward the goal of maximal recombinant protein expression.

* Member of the DEB graduate program

10 COMPANY AFFILIATE: Monsanto, Calgene Campus

IMPROVING CORN GRAIN QUALITY BY BIOTECH ENHANCEMENT OF OIL CONTENT

Presenter: Jill Deikman, Ph.D. Authors: J. Deikman, M. Daley, D. Ke, AO. Patty, M. Ravanello, S. Schwartz Affiliations: Monsanto Company, Calgene Campus Davis, CA 95616

Email: [email protected]

The goal of our project is to improve corn grain quality by increasing oil content. Increasing kernel oil would improve the value of the grain for animal feed, and would allow extraction of oil with increased efficiency. The team is taking a variety of approaches to discover transgenes that will increase kernel oil, including comparison of high oil germplasm to conventional oil germplasm using QTL analysis and gene expression profiling. Study of high oil germplasm led to identification of a dominant mutant allele of the waxy gene that can increase kernel oil when overexpressed in corn kernels. The waxy gene encodes the granule bound starch synthase, and we propose that a slight reduction in starch biosynthesis caused by the mutant protein results in more substrate for oil biosynthesis. This dominant mutation is thought to encode a novel activity, which is under investigation.

11 NIH FELLOW: Allison Dickey

DISQUIETING LIPID BILAYERS VIA ALCOHOL CONTAMINATION: A POSSIBLE MECHANISM FOR ANESTHETIC INTERACTIONS WITH THE NICOTINIC ACETYLCHOLINE RECEPTOR

Presenter: Allison Dickey* Authors: Allison Dickey, Roland Faller Affiliations: Departments of Chemical Engineering and Material Science, University of California, Davis, CA 95616 Preceptor: Roland Faller

We have been examining the interactions between lipid bilayers and various alcohols (ethanol, propanol and butanol) to determine how alcohol chain length and concentration affect alcohol binding location and bilayer mechanical properties. According to Traube's Rule1, the alcohol concentration required to maintain the interfacial tension of a bilayer is reduced by a factor of three for each additional CH2 group added to the alcohol alkyl chain. Recent experimental work2 confirmed Traube’s Rule and we use molecular dynamics to characterize the mechanical properties of the lipid bilayer through parameters such as area per lipid head group, order parameter, and density profile. Using simulations, we examine alcohol/lipid hydrogen bonding dynamics, which are not experimentally accessible3. We calculated the average lifetime of the alcohol/lipid hydrogen bonds for each alcohol chain length and concentration and found that the most frequently recorded alcohol/lipid hydrogen bond location depends on alcohol alkyl chain length.

These alcohol and lipid studies serve as a model for understanding more complex interactions between anesthetics and cellular membranes. One example is the nicotinic acetylcholine receptor, which in the presence of ethanol, enters the desensitized state and results in temporary muscle paralysis.

1. Traube, I. 1891. Ueber die capillaritatsconstanten organischer stoffe in wassriger losung. Ann. Chem. Liebigs. 256:27-55.

2. Ly, H. and M. Longo. 2004. The Influence of Short-Chain Alcohols on Interfacial Tension, Mechanical Properties, Area/Molecule, and Permeability of Fluid Lipid Bilayers. Biophys. J. 87:1013-1033.

3. Dickey, A.N. and R. Faller. 2005. Investigating interactions of biomembranes and alcohols: A multiscale approach. J Polym Sci B 43:1025-1032.

* Member of the DEB graduate program

12 NIH FELLOW: Corey Dodge

PRODUCTION OF RECOMBINANT HUMAN GELATIN IN TRANSGENIC RICE CELL CULTURES

Presenter: CoreyDodge* Authors: Corey Dodge*1, Julio Baez2, Karen A. McDonald1, Mysore Sudarshana3 Affiliations: 1Department of Chemical Engineering and Materials Science University of California at Davis, Davis, CA 2Fibrogen, South San Francisco, CA 3Western Institute for Food Safety and Security, Davis, CA Preceptor: Karen McDonald

Bovine-derived gelatin is used extensively in the manufacturing of pharmaceutical capsules, however the intrinsic variability and safety concerns have prompted the development of recombinant production technologies. Transgenic plants can provide an attractive technology for the production of low cost/high volume industrial proteins such as gelatin. We are developing plant cell culture as a complementary technology to transgenic plants for the fast evaluation of plant-derived industrial recombinant proteins. Stably transformed rice cell lines were generated containing a plant codon optimized gene coding for a fragment of human α(1)-I collagen (100kDa rGelatin) and a rice α- amylase secretion signal peptide under the control of a constitutive maize ubiquitin promoter. Transgenic rice cell cultures were scaled up for production in a 3L bioreactor culture. The maximum extracellular gelatin concentration, as measured by ELISA, was 170 µg/L at 11 days, corresponding to 0.5% of the total extracellular protein. The rGelatin was positively identified by immunoblot following SDS PAGE. Future work will focus on improving bioreactor productivity, improving product quality, and introducing human-like proline hydroxylation of rGelatin through metabolic engineering of the rice cell host.

* Member of the DEB graduate program

13 COMPANY AFFILIATE: SCIOS, Inc.

SCIO-469, A POTENT AND SELECTIVE INHIBITOR OF THE p38α MAPK, INHIBITS TNFα-INDUCED ADHESION OF MULTIPLE MYELOMA CELLS TO BONE MARROW STROMAL CELLS VIA DOWNREGULATION OF CHEMOKINES CXCL10/IP-10 and CCL8

Presenter: Aaron N. Nguyen, Ph.D. (DEB graduate) Authors: Aaron N. Nguyen, Gilbert O’Young, Diana Ouon, Debby Damm, Ann M. Kapoun, Linda S. Higgins, and Tony A. Navas Affiliations: Scios Inc., Fremont, CA Email: [email protected]

Multiple myeloma (MM) is a plasma cell cancer characterized by the accumulation and clonal expansion of malignant cells in the bone marrow (BM). Recent findings indicate that adhesion of MM cells to BM stromal cells (BMSCs) protects MM cells from drug- induced apoptosis and leads to upregulation of interleukin-6 (IL-6), a cytokine that promotes MM cell growth and survival. However, the molecular mechanism that determines the adhesion of MM cells to BMSCs is relatively unclear. Here we show that SCIO-469, a potent and selective inhibitor of the p38 α mitogen-activated protein kinase (MAPK), prevents TNF α -induced adhesion of MM cells to BMSCs. Interestingly, TNF α -induced expression of ICAM-1 and VCAM-1, molecules that have been reported to mediate cell-cell adhesion, is not affected by SCIO-469 treatment. In an effort to identify additional factors that may play a role in the adhesion of MM cells to BMSCs, we performed a DNA microarray experiment on BMSCs. Of the BMSC genes that were strongly upregulated by TNF α exposure and reversed by SCIO-469 treatment, a set of chemokines was most prominent. To determine whether these chemokines are important for MM adhesion to BMSCs, various chemokines (CCL2, CCL7, CCL8, CXCL1, CXCL3, CXCL6, CXCL10/IP-10, and CXCL11) were added together with SCIO-469 in the adhesion assays. We found that reintroduction of the chemokines CXCL10 and CCL8 reversed the inhibition of adhesion by SCIO-469. These results suggest that SCIO-469 inhibits TNF α -induced adhesion of MM cells to BMSCs by downregulating the chemokines CXCL10 and CCL8. Intriguingly, these two chemokines were also recently demonstrated to be involved in leukocyte adhesion to endothelial cells. Thus, chemokines, especially CXCL10 and CCL8, appear to have a general function of localizing blood cells to various sites within the body. Together, our findings demonstrate another potential therapeutic role for SCIO-469 in MM in addition to its role of inhibiting the production of growth promoting factors such as IL-6 and VEGF in the MM bone marrow microenvironment.

14 NIH FELLOW: Suzanne Barber (formerly Balko)

BILATERAL DIFUNCTIONAL NANOSPHERE AGGREGATES TO CONSTRUCT BIOSENSORS AND THEIR APPLICATION TO LIGAND RECEPTOR BINDING INTERACTIONS

Presenter: Suzanne Barber* Authors: Suzanne Barber*1, Philip J. Costanzo2, Nathan W. Moore1, Timothy E. Patten2 and Tonya L. Kuhl1 Affiliations: 1Department of Chemical Engineering and Materials Science and Department of Chemistry, 2University of California-Davis, One Shields Ave, Davis, CA 95616 Preceptor: Tonya Kuhl

We have developed an efficient method for producing difunctional, bilateral nanospheres/nanoparticles of various materials, including superparamagnetic and ferromagnetic materials. By variation of the base particle and metal deposited onto the surfaces of the nanoparticles, bilateral nanoparticles were formed. The different regions of the nanoparticles were selectively functionalized with polymer linkers containing specific terminal groups, thereby creating bilateral, difunctional nanoparticles. Subsequent covalent cross-linking of different nanoparticles enabled the formation of stable architectures with programmed hierarchy and controlled chemical composition. We propose that by modulating the length and chemical composition of the polymer linker and its binding energy to the particles, the interaction potential between particles can be specified. This ability to fine-tune the interaction energy of the system is a key aspect for creating novel hierarchical materials for specific applications, including development of a biosensor for the measurement of receptor-ligand binding interactions. We construct biosensors for the detection of ligand-receptor binding events utilizing magnetic particles. We show preliminary data indicating the efficiency of such a biosensor construction and propose its use for measurement of ligand-receptor binding strength and binding affinity.

* Member of the DEB graduate program

15 NIH FELLOW: Jennifer Warren

UTILIZING PALM® LMPC TO ISOLATE SINGLE CELLS FROM MICROBIAL BIOFILMS FOR GENE EXPRESSION ANALYSIS

Presenter: Jennifer Warren* Authors: Jennifer Warren*, Marko Estrada, and Stefan Wuertz Affiliations: Department of Civil and Environmental Engineering, University of California Preceptor: Stefan Wuertz

Conjugative gene transfer, the delivery of plasmid DNA through direct cell to cell contact, offers great potential for the remediation of persistent chemical contaminants through the transfer of catabolic genes to indigenous microbial populations. However, many questions persist about the process of conjugation and its effect on biofilm function. The main objective of this research is to investigate the expression of catabolic genes in transconjugants. To study individual transconjugants, it is necessary to be able to identify and extract single cells from the biofilm. PALM® LMPC is a novel technology that utilizes lasers to achieve contact free isolation of cells or biological entities. However, LMPC has not been utilized with microbial biofilms, which present some complex obstacles. Experiments have been conducted to determine the efficacy of isolating single cells from biofilms with LMPC. Biofilms of fluorescently labeled cells were grown in flow cells that are amenable to in situ analysis using a Confocal Laser Scanning Microscope (CLSM) and the LMPC system. 1, 4, and 10 target cells were catapulted from a pure culture biofilm and analyzed using real time PCR. Samples were found to contain 103, 25, and 123 gene copies, respectively. Results demonstrate that non-target cells are also being catapulted and that multiple catapulting events will need to be conducted on the catapulted cell suspension in order to obtain the single target cell. Catapulting of 5 individual cells from a suspension of cells resulted in the procurement of a total of 10 cells, which suggests that isolation of a single target cell is feasible. Additionally, a biofilm study was conducted to investigate if the membrane necessary for LMPC affects biofilm development and conjugation. CLSM images of the biofilms were analyzed with PHLIP image analysis software and biofilm parameters were calculated. The total biovolume was determined to be 54,987 μm3 and 84, 672 μm3 and the percent of transconjugants was determined to be 0.84% and 1.26% for the biofilm grown with and without the membrane, respectively. These results demonstrate the LMPC membrane does indeed affect biofilm development and conjugation events. However, this difference could be negligible if biofilms grown on membranes are reproducible, and this will be investigated in the future.

* Member of the DEB graduate program

16 COMPANY AFFILIATE: CHIRON

HIV VACCINE RESEARCH AND DEVELOPMENT AT CHIRON VACCINES

Presenter: John Donnelly, Ph.D. Authors: John Donnelly, Indresh Srivastava, Michael Vajdy, John Polo, Jeff Ulmer, and Susan Barnett Affiliations: Chiron Vaccines Research, Emeryville, CA 94608 Email: [email protected]

Chiron Corporation is a biotechnology company headquartered in Emeryville, CA, with three business units: Blood Testing, Biopharma, and Vaccines. Total corporate revenues in 2005 were approximately $2 Billion. The Vaccines Business Unit, headquartered in Oxford, England, also has sites in Liverpool, Marburg, Germany, Siena, Italy, and Emeryville, CA and is a leading supplier of influenza vaccines worldwide. Chiron’s involvement in HIV research dates to the discovery of the virus Since 2000 Chiron has conducted an HIV Vaccines Research and Development Program sponsored in part by the NIH. Our overall vaccine approach is to integrate cellular and humoral immune responses by combining priming with a gene delivery platform and boosting with a recombinant Env protein engineered to expose conserved epitopes in the coreceptor binding region. We developed two gene delivery platforms for priming, based on DNA vaccines formulated with PLG microparticles, and on a novel chimeric alphavirus replicon particle. The PLG-DNA prime and env protein boost concept is being tested in a Phase I clinical trial by the NIH-sponsored HIV Vaccines Trials Network. The chimeric alphavirus replicon platform is being prepared for clinical testing under an NIH contract. Our selection criteria for the advancement of these technologies is the induction of potent, durable cellular immune responses, the induction of crossreactive neutralizing antibodies, and the ability to demonstrate protection in nonhuman primate challenge models. Supported in part by NIH contracts N01-AI-25473, N01-AI-05396, and N01-AI- 50007

References: 1) zur Megede, et. al. 2) Denis-Mize, et. al. 3) Vajdy M, Singh, et. al. 4) Otten GR, et. al.

17 BIOTECH FELLOW: Laura Higgins

DIFFERENTIAL EFFECTS OF FASTING AND POSTPRADIAL VLDL ON MONOCYTE ACTIVATION

Presenter: Laura Higgins* Authors: Laura Higgins*, Laura J Higgins, John C Rutledge Affiliations: Department of Internal Medicine, University of California, Davis, Davis, CA

Preceptor: John Rutledge

The interactions between lipids and monocytes are fundamental to the development of atherosclerosis. Postprandial lipemia is characterized by increased circulating triglyceride-rich lipoproteins, including chylomicrons and very low density lipoproteins (VLDL), and prolonged exposure of these lipids and their lipolysis products to vascular cells is thought to promote atherosclerosis. Little is known about the mechanism by which the postprandial state can induce vascular inflammation, in particular monocyte activation. We hypothesized that postprandial VLDL lipolysis products preferentially activate monocytes in vitro relative to fasting lipids. Blood was collected from human volunteers before and after consumption of a moderately high fat meal and VLDLs were isolated by ultracentrifugation. Fasting and postprandial VLDL lipolysis products (250 mg triglycerides/dL + 2 U/mL lipoprotein lipase) were incubated with THP-1 monocytes in combination with lipopolysaccharide (LPS, 3 μg/mL) for four hours, and secreted tumor necrosis factor-α (TNFα) gene expression and protein were quantified. Fasting VLDL lipolysis products attenuated LPS-induced TNFα secretion by 15-fold compared to LPS alone (131.3 ± 67.9 vs. 1966.5 ± 118.5 pg/mL, P<0.001, respectively), while the postprandial fraction decreased LPS-induced TNFα secretion by only 3-fold compared to LPS alone (638.8 ± 77.3 pg/mL vs. 1966.5 ± 118.5, P<0.001). Preincubation of a polyclonal apolipoprotein E (apoE) antibody during the postprandial VLDL lipolysis reaction increased the TNFα inflammatory response to LPS 2-fold (1107.1 ± 152.0 vs. 638.8 ± 77.3 pg/mL, p<0.008). This suggests that apoE partially sequesters LPS, and therefore prevents its interaction with monocytes. This 5-fold increase in TNFα secretion indicates that postprandial VLDL lipolysis products possess proinflammatory properties lacking in the fasting fraction. Repetitive activation of circulating monocytes by regular consumption of high fat meals could accelerate atherosclerotic cardiovascular disease.

* Member of the DEB graduate program

18 COMPANY AFFILIATE: Novozymes, Inc.

A BETTER BETA-GLUCOSIDASE FROM A. ORYZAE FOR THE CONVERSION OF BIOMASS TO ETHANO

Presenter: Aubrey Jones Authors: Aubrey Jones Affiliations: Novozymes, Inc., 1445 Drew Ave., Davis, CA 95616 Email: [email protected]

Plant biomass, including the cellulosic material comprising cell walls of higher plants, is the most abundant source of fermentable carbohydrates in the world and as of yet, a barely-utilized renewable energy resource. Utilization of this carbohydrate for biofuel (ethanol) depends on our ability to cheaply and efficiently convert the complex carbohydrate into sugar. The conversion of cellulosic biomass to fermentable glucose requires the coordinated action of several enzymes that include endocellulases, exocellulases and β -glucosidase. The glycosyl hydrolase family 3 β -glucosidase catalyzes the conversion of cellobiose to glucose and is thought to be one of the major rate-limiting steps in the saccarification of celluloase. Given this key role, we set out to improve the performance of β -glucosidase from the filamentous fungi Aspergillus oryzae. Here we describe our work to increase the thermostability and the heterologous expression of A. oryzae β -glucosidase to enhance biomass to ethanol production.

19 BIOTECH FELLOW: Riccardo LoCascio

SELECTIVE HUMAN MILK OLIGOSACCHARIDE CONSUMPTION BY BIFIDOBACTERUM INFANTIS ATCC 15697

Presenter: Riccardo LoCascio* Authors: Riccardo G. LoCascio1-4*, Milady Ninonuevo2, J. Bruce German3, Carlito B. Lebrilla2 and David A. Mills1 Affiliations: 1Department of Viticulture & Enology, University of California, Davis, 95616 2Department of Chemistry, University of California, Davis, 95616 3Department of Food Science & Technology, University of California, Davis, 95616 4Microbiology Graduate Group, University of California, Davis, 95616

Preceptor: David Mills

Bifidobacteria spp. are the predominant microbial species in gastrointestinal tracts of infants and are associated with a number of beneficial health effects, such as a reduced incidence of diarrheal illnesses, improved lactose digestion and enhanced immunomodulation. We have previously shown that bifidobacteria can ferment human milk oligosaccharides, suggesting that these molecules function as prebiotics for selective amplification of bifidobacterial populations in infants. To understand the genetic basis for bifidobacteria metabolism of these oligosaccharides, quantitation and characterization of human milk oligosaccharides is extremely important but remains a difficult task. To date our research group has examined growth of Bifidobacterium longum, B. infantis and B. breve on human milk oligosaccharides as their sole carbon source and analyzed the remaining oligosaccharide constituents using mass spectrometry. Here we report that B. infantis ATCC 15697 utilized mostly fucosylated human milk oligosaccharides for growth. Specifically, this strain selectively consumed smaller chains human milk oligosaccharides at its initial growth stage, while longer chain oligosaccharides were only utilized during stationary phase. Characterization of the oligosaccharide consumption preferences for B. longum and B. breve is ongoing. To define the underlying genetic basis for growth on these unique substrates, we will be examining the expression of bifidobacterial ABC-type oligosaccharide transporters and of glycosyl hydrolases.

* Member of the DEB graduate program

20 BIOTECH FELLOW: Vu Bao Trinh

APTAMER CONTROLLED RNAi-BASED GENETIC SWITCHES

Presenter: Vu Bao Trinh* Authors: Vu B. Trinh*, Chung-Il An, and Yohei Yokobayashi

Affiliations: Department of Biochemistry and Molecular Biology and Department of Biomedical Engineering, University of California, Davis, California 95616, USA Preceptor: Yohei Yokobayashi

RNA interference (RNAi) has been used as a powerful tool to silence gene expression in mammalian cells. We recently developed a novel strategy for post-transcriptional gene regulation in mammalian cells by modulating RNAi with a small molecule. Using a theophylline aptamer-fused short hairpin RNAs (shRNAs), Dicer-mediated cleavage of the shRNA is inhibited upon binding theophylline, resulting in theophylline-induced expression of a trans gene. We are also developing other strategies for regulating RNAi by engineering ribozymes and microRNA-based vectors to control mammalian gene expression in response to various aptamer ligands. These ligand-responsive genetic switches based on RNA may provide new insights into the molecular biology of RNAi as well as its applications.

* Member of the DEB graduate program

21 COMPANY AFFILIATE: Amgen Inc.

CORPORATE OVERVIEW OF AMGEN AND THE ROLE OF FORMULATION IN THE PRODUCTION OF PROTEIN HUMAN THERAPEUTICS

Presenter: Douglas D. Banks,Ph.D. Authors: Douglas D. Banks, Affiliations: Department of Pharmaceutics, Amgen Inc., Thousand Oaks, CA 91320 Email: [email protected]

Amgen started in 1981 with a broad focus on Applied Molecular Genetics (AMGEN). However, it was in 1984 when Amgen became a billion-dollar Biopharmaceutical due to the successful cloning of the erythropoietin gene, which led to the production of Epoetin alfa known as EPOGEN. By the turn of the century Amgen has become a modality independent Human Therapeutic company that continues to develop the best practices in research and manufacturing. Strong Amgen values such as being science-based, ensuring quality, and competing intensely to win have allowed Amgen to serve over eight million patients.

Our mission in the Pharmaceutics Department at Amgen is to develop formulations and delivery systems for Amgen’s clinical and marketed products and to support discovery research as needed with preclinical characterization and formulations. Formulation development is one of the critical steps in developing a protein as a therapeutic product. Because proteins are complex molecules composed of numerous reactive chemical groups and delicate three-dimensional structures, identifying a set of conditions to keep all components stable is a tremendous challenge and virtually impossible. Therefore, the main objective becomes one of maintaining the appropriate efficacy and safety of the protein product. In order to achieve this objective, it is imperative to develop an in-depth understanding of protein properties and the broad spectrum of degradation pathways affecting protein stability.

To this end our formulation development focuses on determining the potential degradation pathways assessing the significance of each and optimizing variables to minimize the degradation products that are clinically significant.

22 BIOTECH FELLOW: Vannarith Leang

USING NMR TO STUDY HYDRODYNAMIC FACTORS AFFECTING COALESCENCE OF EMULSIONS

Presenter: Vannarith Leang* Authors: Vannarith Leang*, Robert Powell, Stephanie Dungan, and Ronald Phillips

Affiliations: Department of Chemical Engineering, University of California, Davis, CA 95616 Preceptor: Robert Powell

An emulsion is a thermodynamically unstable mixture of two immiscible fluids with one fluid being dispersed in the other. Coalescence, which is the fusion of two similar size drops to form a lager drop, is one of several emulsion breakdown methods. The coalescence mechanism can be broken into four distinct steps: Collision, Film Drainage, Film Rupture, and Confluence. These four steps happen sequentially with each step having a certain time scale to occur. Our research will focus on the first two steps which are dominated by hydrodynamic forces. We’ve developed a dimensionless ratio (Φ) to describe the time it takes for Film Drainage with respect to Collision. Using Φ, we will be able to predict how certain parameters will change the rate of coalescence. The rate of coalescence will be directly related to the change in drop size of the system, which will be measured by NMR through the use of the restricted diffusion theory. NMR is non- invasive, insensitive to volume fraction, and can distinguish one big drop from a cluster of small drops, unlike light scattering. Preliminary results using a mixture of octane, water, and Tween 20 indicates the scaling is correct with the shear rate in that an increase in shear rate leads to a decrease coalescence rate. Further work will be done in changing the other system properties.

γ&μReq =Φ )( 2/1 σ

* Member of the DEB graduate program

23 COMPANY AFFILIATE: GENENTECH, INC.

To Be Announced

Bioethics

ETHICS QUESTION

Can You Tell If a Science Publication Isn’t Authentic?

Handouts to be presented at Retreat with discussion following

Martina Newell-McGloughlin Co-Director of NIH Training Grant in Biomolecular Technology

(NIH-1-T32-GM08799)

Poster Abstracts

27 A. HOMING SITE REQUIREMENTS OF THE LACTOCOCCAL GROUP II INTRON IN ITS NATIVE HOST

David A. Sela*, Helen Rawsthorne, and David A. Mills Department of Viticulture and Enology, University of California, Davis, CA 95616

The Lactococcus lactis group II intron (Ll.ltrB) has been demonstrated to retrohome into the ltrB gene at high efficiency. To date, the critical DNA bases recognized in vivo by the Ll.ltrB ribonucleoprotein (RNP) have been exclusively elucidated in Escherichia coli. However, recent evidence indicates host-dependant differences in Ll.ltrB mobility, suggesting limitations of the current model for RNP-homing site recognition in a L. lactis host. A quantitative real-time PCR (QPCR) assay was developed to test target site nucleotides, previously demonstrated as critical for homing in E. coli, for relevance in L. lactis. A series of Ll.ltrB target site variants were constructed and co-introduced with the wild type intron into L. lactis. This two-plasmid QPCR homing assay is highly sensitive and, unlike the E. coli assay, resolves differential homing efficiencies in the absence of selection. Preliminary data indicates that bases critical for efficient homing in L. lactis mirror those that have been previously described in E. coli. Specifically, deviation from wild type at target site positions -23, -21, -20, -19, and +5 has generally resulted in a lower homing efficiency of Ll.ltrB. Our results suggest that these target site positions are critical in both E. coli and L. lactis and host-related differences observed with Ll.ltrB homing arise from additional, yet uncharacterized, factors.

* Member of the DEB graduate program

28 B. ENGINEERING OILSEED CROP NUTRITION

Henry E. Valentin1, Balasulojini Karunanandaa2, Qungang Qi2, Alison Van Eenennaam1, Eric Aasen1, Charlene Levering1, Christine Shewmaker1, Susan Norris2, Kim Lincoln2, Rob Last2, Ming Hao2,Susan Baszis2, Pamela Jensen2, Yun- Hua Wong2, JianJiang2, Farhad Moshiri2, Aundrea Warren2, Mylavarapu Venkatramesh3, Kenneth J. Gruys1.Jennifer Gonzales, AJ Nava, Janet Nelsen, Jeff Haas, Virginia Ursin 1 Monsanto Company, Calgene Campus 2 Monsanto Company 3 Renessen LLC

Tocopherols are the most important lipid soluble antioxidants for animals and humans and are an essential part of the mammalian diet. In plants, tocopherols are thought to stabilize the plant specific extensive membrane structures, and storage lipids from molecular decay of fatty acid double bonds through oxygen radicals. Oil seed are particularly rich in tocopherols with an average of 10-fold the concentrations found in other plant tissues. Feeding experiments performed with soybean suspension cultures and canola developing embryos revealed homogentisic acid and phytyldiphosphate as critical intermediate pools for tocopherol biosynthesis. Key genes to increase these intermediates were expressed in Synechocystis PCC 6803 as single genes, or in combination resulting in > 16-fold total tocopherol content for the best performing gene combination. Expression of these genes in soybean seed resulted in up to 4806 ng/mg total tocopherols, a 15-fold increase compared to wild type soybean seed. New insights on the tocopherol biosynthetic pathway that were gained through the experiments performed, as part of this metabolic engineering project will be presented.

29 C. LIPOLYSIS PRODUCTS ALTER PROTEIN AND LIPID STRUCTURAL CHARACTERISTICS IN THE PLASMA MEMBRANES OF HUMAN MONOCYTES

Laura J Higgins1*, Nabil M Saad2, Oliver Fiehn2, John C Rutledge1 1Dept of Internal Medicine, 2Genome Center, University of California, Davis, 95616

The interactions between lipids and monocytes are fundamental to the development of atherosclerosis. Postprandial lipemia is characterized by increased circulating triglyceride-rich lipoproteins (TGRLs). Prolonged exposure of these lipids and their lipolysis products to cellular membranes is thought to promote atherosclerosis. We hypothesize that TGRL lipolysis products activate monocytes, generating novel cellular phenotypes that predict atherosclerosis. We investigated this hypothesis by treating primary human monocytes with either TGRL lipolysis products (150 mg/dL TG + 3 U lipoprotein lipase) or media for 3.5 hours. Fourier transform infrared radiation (FTIR) spectra of the amide signature region were obtained from treated and untreated cells, and their metabolic signatures determined by direct nano-electrospray ionization FT-MS. FTIR spectra of TGRL-treated cells revealed a spectral signature characterized by proteins with increased β-sheet conformations, possibly due to changes in inflammatory marker expression. FT-MS analysis showed an increase in phosphatidylcholine and desaturases in TGRL-treated cells, indicating changes in membrane fluidity. These results demonstrate that lipid lipolysis products exert drastic changes on monocyte surfaces and may contribute to the development of monocyte signatures that could predict atherosclerosis. This research was partially supported by a fellowship under the Training Program in Biomolecular Technology (T32-GM08799) at the University of California, Davis.

* Member of the DEB graduate program

30 D. IMMUNOPHENOTYPING OF LEUKOCYTES ON ANTIBODY MICROARRAYS

He Zhu*, Kazuhiko Sekine, Mehmet Toner, and Alexander Revzin Section of Microbiology, University of California, Davis, CA, 95616

Leukocytes are a heterogeneous mixture of several cell subsets Leukocyte subset proportions provide critical clinical information. For example, the proportions of CD4+ to CD8+ T-lymphocytes, and absolute CD4 cell counts are diagnostic markers of HIV. Flow cytometry, considered as the “gold” technology for the analysis of leukocyte subset proportions, has several limitations including large quantity of samples, long pre- treatment time of the sample cells and inability of tracking specific cells. In this study, a new method is demonstrated capable of complementing these shortcomings of flow cytometry. CD4+ T-lymphocytes, CD8+ T-lymphocytes, CD36+ monocytes and CD16b+ neutrophils were characterized in this study. Antibodies specific for these leukocytes, namely, CD4, CD8, CD36, CD16b, anti-mouse IgG (negative control), and poly-lysine (positive control) were printed by a robotic microarrayer on a standard 75×25×1mm microscope glass slide coated with a thin uniform film of poly (ethylene glycol) hydrogel (PEG). PEG coating proved to be effective in eliminating non-specific leukocyte adhesion to the glass surface. The high-throughput robotic microarrayer yielded arrays of 150 μm spots in diameter. After incubation of PEG-coated, antibody-modified glass slide with red blood cell (RBC) depleted whole blood, the glass slide was placed in a parallel- plate flow chamber for controlled washing. Non-specifically deposited cells were removed by the shear force of the flow while selectively captured cells remained on their corresponding antibody spots. The captured cells were immuno-fluorescently stained to determine their phenotype. Because of the small size of the antibody spots, the number of cells on each antibody domain was easily counted and a ratio of phenotypically different subsets was obtained. Neutrophils, monocytes, CD4+ T-lymphocytes and CD8+ T- lymphocytes were thus captured and identified on respective antibody domains with purity exceeding 98%. Therefore, the proposed cytometry platform can quickly determine leukocyte subset proportions and absolute counts of CD4 T-cells with minimal sample preparation and handling. This platform will be applicable for future HIV testing and monitoring.

* Member of the DEB graduate program

31 E. HIGH AFFINITY HIGH SPECIFICITY ALPHA4 BETA1 INTEGRIN TARGETING PEPTIDES FOR LYMPHOID CANCERS

L. Peng*, R. Liu, X. Wang, J. Marik, Y. Takada, K. S. Lam Department of Internal Medicine, UC Davis Cancer Center, University of California Davis, 4501 X Street, Sacramento, California 95817

Alpha4 beta1 integrin plays an important role in inflammation, cancer development, and metastasis. Blocking alpha4 beta1 interactions with vascular cell adhesion molecule-1 and fibronectin has been used as a therapeutic strategy for inflammation and autoimmune diseases. A growing body of literature suggests that alpha4 beta1 integrin may be an excellent target for imaging and treatment of lymphoid malignancies. The one-bead one- compound (OBOC) combinatorial library method offers a powerful technique to identify and optimize cancer-specific peptides. Here we report on the design and synthesis of a focused OBOC peptidomimetic combinatorial library, in conjunction with a high stringency cell-based screening method, to rapidly optimize the LDV binding motif for alpha4 beta1 integrin. Using this approach, high-affinity high-specificity targeting peptidomimetics against activated alpha4 beta1-integrin on both T- and B-lymphoma cells have been identified. The molecular interactions between the targeting agents and a number of alpha4 beta1 mutant cell lines were analyzed by flow cytometry, and we were able to show that Trp188 and Gly190 are crucial for binding. Furthermore, using a murine xenograft model we demonstrated that one of these ligands, when conjugated to a near infrared dye, was able to image lymphoma with high sensitivity and specificity

* Member of the DEB graduate program

32 F. α-TUBULIN DETYROSINATION: A MOLECULAR SWITCH FOR REGULATING VASCULAR SMOOTH MUSCLE CELL PROLIFERATION

Anh D. Phung1*, Karel Souček1, Lukáš Kubala1, Richart W. Harper1, J. Chloë Bulinski4,5 & Jason P. Eiserich1, 2, 3 1Department of Internal Medicine, 2Department of Physiology and Membrane Biology, and 3Cancer Center, University of California, Davis, California 95616 USA. 4Department of Biological Sciences and 5Department of Pathology & Cell Biology, Columbia University, New York, NY 10027, USA.

Hyperproliferation of vascular smooth muscle cells is a hallmark of atherosclerosis and related vascular complications. Microtubules are important for many aspects of mammalian cell responses including growth, migration and signaling. α-Tubulin, a component of the microtubule cytoskeleton, is unique amongst cellular proteins in that it undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-Tubulin) and re-added (Tyr-Tubulin). Whereas the reversible detyrosination/tyrosination cycle of α-tubulin has been implicated in regulating different aspects of cell biology, the precise function of this posttranslational modification has remained poorly characterized. Herein, we provide evidence suggesting that α-tubulin detyrosination is a required event in the proliferation of vascular smooth muscle cells. Proliferation of rat aortic smooth muscle cells in response to serum was temporally associated with the detyrosination of α-tubulin; Glu-tubulin reached maximal levels between 12 - 18 hrs following cell cycle initiation. Inclusion of 3-nitro-L-tyrosine (NO2Tyr) in the culture medium resulted in the dose-dependent nitrotyrosination of α- tubulin, that was paralleled by decreased elaboration of Glu-tubulin, decreased expression of cyclins A and E, decreased association of the microtubule plus-end binding protein EB1, and inhibited cell proliferation. Nitrotyrosination of α-tubulin did not induce significant cell death of rat aortic smooth muscle cells but instead led to cell cycle arrest at the G1/S boundary coincident with decreased DNA synthesis. 3-Nitro-4- hydroxyphenylacetic acid, a nitrophenol analog of NO2Tyr that is incapable of being incorporated into α-tubulin, had no significant effect on Glu-tubulin level, cyclin expression, or proliferation. Collectively, these results suggest that α-tubulin detyrosination plays a functionally important role as a molecular switch for regulating cell cycle progression.

* Member of the DEB graduate program

33 G. Novel Biofunctional Core/Shell Quantum Dots for Multimodality Imaging

Heather A. Palko1+, Zane S. Starkewolfe1*+, Shizhong Wang1,3, Li Peng2*, Kit S. Lam2, Angelique Y. Louie3 1Department of Chemistry, University of California, Davis, CA 95616 2Divison of Hematology and Oncology, Department of Internal Medicine, University of California, Davis, CA 95616 3Department of Biomedical Engineering, Chemistry Graduate Group, University of California, Davis, CA 95616

+ These authors contribute equally to this work

Multimodality imaging probes have become increasingly popular in vivo and in vitro biological systems. CdSe/ZnS Core/Shell quantum dots offer an optical platform in which PET, CT, and MRI contrast agents can be incorporated into the shell or coupled to the surface. Quantum dots typically range from 4-8 nanometers in diameter with narrow emission bandwidth dependant upon size. The ZnS shell of the quantum improves the quantum yield, while preventing degradation of the core. We are developing luminescent/paramagnetic dual modality quantum dots for optical/MRI imaging. Doping of 0.7 – 7.4% Mn2+ in the ZnS shell provides an observable MRI signal, while maintaining strong luminescence and high quantum yield. These CdSe/ZnS Mn2+ doped quantum dots have been synthesized and will be used for cancer diagnostics, plaque characterization, and pollutant distribution in the respiratory system. For example, CdSe/ZnS quantum dots with these characteristics are functionalized using peptidomimetic ligands (2A) and (OA02) that bind the α4ß1 and α3ß1 integrins on the surface of lymphoma and ovarian cancer cells. This bioimaging targeting agent provides an important tool to non-invasively monitor cancer progression and response to therapy.

* Members of the DEB graduate program

34 H. ENGINEERING OILSEED CROP NUTRITION

*Henry E. Valentin1, Balasulojini Karunanandaa2, Qungang Qi2, Alison Van Eenennaam1, Eric Aasen1, Charlene Levering1, Christine Shewmaker1, Susan Norris2, Kim Lincoln2, Rob Last2, Ming Hao2,Susan Baszis2, Pamela Jensen2, Yun-Hua Wong2, JianJiang2, Farhad Moshiri2, Aundrea Warren2, Mylavarapu Venkatramesh3, Kenneth J. Gruys1 1 Monsanto Company, Calgene Campus. 2 Monsanto Company 3 Renessen LLC

Company Affiliates

Company Affiliates** Support Biotech at UC Davis

Agilent Technologies Amgen, Inc. Berlex Biosciences Chiron Corporation Genentech, Inc. Monsanto, Calgene Campus Novozymes, Inc Scios, Inc.

**These Biotechnology companies have donated at least $20,000 per year for a Biotechnology fellowship and/or have offered an internship site for our DEB graduate students and have presented at the annual Biotechnology Training Retreat. Company representatives also serve as advisors for training grants and other educational programs.

The success of our program depends on the continued support of our affiliates and the Biotechnology Program would like to thank them for their continued support.

37 Agilent Technologies Contact: David Hirschberg, Ph.D., Scientist 3500 Deer Creek Road Palo Alto, CA 94304 650-485-2120 www.agilent.com [email protected]

Agilent delivers critical tools and technologies that sense, measure and interpret the physical and biological world. Our innovative solutions enable a wide range of customers in communications, electronics, life sciences and chemical analysis to make technological advancements that drive productivity and improve the way people live and work. Our life sciences and chemical analysis business provides application-focused solutions that include instruments, software, consumables and services that enable customers to identify, quantify and analyze the physical and biological properties of substances and products.

Our seven key product categories include microarrays; microfluidics; gas chromatography; liquid chromatography; mass spectrometry; software and informatics products; and related consumables, reagents and services.

38 Amgen, Inc Contacts: Gerd R. Kleemann, Ph.D., Research Scientist Douglas Banks, Ph.D., Research Scientist One Amgen Center Drive Thousand Oaks, CA 91320-1799 Phone: 805-447-1000 www.amgen.com [email protected] [email protected]

Amgen is a leading human therapeutics company in the biotechnology industry. For 25 years, the company has tapped the power of scientific discovery and innovation to dramatically improve people’s lives. Amgen pioneered the development of novel products based on advances in recombinant DNA and molecular biology and launched the biotechnology industry’s first blockbuster medicines. Today, as a Fortune 500 company serving millions of patients, Amgen continues to be an entrepreneurial, science- driven enterprise dedicated to helping people fight serious illness.

Over the past quarter century, Amgen has pioneered the methods by which human proteins that play a role in disease processes are identified, isolated, produced in quantity and used as therapeutics. Today, Amgen has research programs in inflammation, metabolic disorders and osteoporosis, neurology, oncology and hematology. The company has R&D facilities in Thousand Oaks, CA; San Francisco, CA; Cambridge, MA; Cambridge, UK; Regensburg, Germany; and Seattle, WA. With expertise in proteins, small molecules, antibodies, peptibodies, and nucleic acids, Amgen’s scientists can pursue the study of disease, choose the best target for a disease and then use the modality most likely to have an effect on that target. This approach positions Amgen as one of the only companies with capabilities across a range of modalities. Mastering the tools of therapeutic development, as they emerge, is crucial to Amgen’s ongoing success. Accordingly, the company has invested at least 20 percent of product sales in research and development each year since 1994—a total of approximately $2.0 billion in 2004.

39 Berlex Biosciences Contacts: Gordon Parry, Ph.D., Chief Scientist Richard Harkins, Ph.D., Scientific Director 2600 Hilltop Drive Richmond, CA 94806 www.berlex.com [email protected] [email protected]

Berlex's singular approach to developing and making specialized medicines already has yielded innovations in treating multiple sclerosis, dermatological disorders, female health concerns, cancer and in the creation of new diagnostic imaging techniques. For the future, the pipeline of new products and the potential for developing better treatments will help make medicine work for those who need it most in the years ahead.

Whether you are a patient or caregiver, a physician, an investor, a job-seeker, or a neighbor, we hope this section will give you the information you need about the medicines we make today, and about the responsibility we have to the communities where we operate and to the families whose lives we touch.

40 Chiron Corporation Contacts: John Donnelly, Ph.D., Senior Director Eddie Moler, Ph.D., Principal Scientist, Research Indresh Srivastava, Ph.D., Assoc. Director, Imm. & Cell Biology; Vaccines Research 4560 Horton Street Emeryville, CA 94608-2916 www.chiron.com [email protected] [email protected] [email protected]

Mission Chiron strives to be a leading biotechnology company by creating products that transform human health worldwide. We aim to prevent and treat diseases and improve people’s lives.

Leadership Strategy We will accomplish our mission through technological leadership, product-oriented research, superior manufacturing, and commercial strategies that create and expand markets.

Ethical Standards We adhere to the highest legal and ethical principles in the conduct of all aspects of our business. We are committed to adhering to proven standards of financial and operational performance.

Values Our purpose is to find solutions to human suffering caused by disease. Because disease does not wait for solutions, we are driven by a sense of urgency. As a result, our environment is intense, challenging, and focused on creating value for those who use our products and delivering sustained profitable growth for those who invest in our company.

Quality Our goal at Chiron is to deliver quality products and services on time to all customers, internal and external. We provide employees with training and resources to meet or exceed customer requirements. We monitor processes and products to identify opportunities for continuous improvement.

41 Genentech, Inc. Contact: Vishva Dixit, Ph.D., Vice President, Staff Scientist Melody Trexler Schmidt, Ph.D., (DEB Graduate), Scientist 1 DNA Way South San Francisco, CA 94080-4990 www.gene.com [email protected] [email protected]

Genentech is a leading biotechnology company that discovers, develops, manufactures, and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from, or are based on, Genentech science. Genentech manufactures and commercializes multiple biotechnology products directly in the United States and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is traded on the New York Stock Exchange under the symbol DNA.

Corporate Overview Genentech, the founder of the biotechnology industry, is a company with a quarter- century track record of delivering on the promise of biotechnology. Today, Genentech is among the world's leading biotech companies, with multiple protein-based products on the market for serious or life-threatening medical conditions and over 30 projects in the pipeline. With its strength in all areas of the drug development process — from research and development to manufacturing and commercialization — Genentech continues to transform the possibilities of biotechnology into improved realities for patients.

Marketed Products: Delivering innovative medicines to patients with serious or life-threatening medical conditions is what Genentech is all about. Since its beginning in 1976, the company has focused its drug discovery efforts on therapies that would fill unmet needs. Today, Genentech manufactures and commercializes multiple protein-based biotherapeutics for serious or life-threatening medical conditions — giving Genentech one of the leading product portfolios in the biotech industry.

Development Pipeline: As a biotechnology leader, Genentech has a long-standing tradition of reinvesting a significant percentage of revenues back into research and development — a practice that has proved successful in transforming promising candidates into important new products. With the projects below under way, Genentech's development pipeline has never been more robust and promising. More than half of Genentech's pipeline is composed of potential antibody therapies.

42 Mosanto Contact: Kenneth Gruys, Ph.D., Science Director, Site Manager 1920 Fifth Street Davis, CA 95616 www.monsanto.com [email protected]

Calgene was founded in 1980 and is perhaps best known for the development of the first commercialized genetically engineered food, the FLAVR SAVR tomato. Monsanto acquired Calgene in 1997 and it is now a research and development site within Monsanto AG. Current research at Calgene focuses primarily on improving quality traits for feed and food, as well as nutritional approaches for the enhancement of health. Calgene has approximately 100 employees and it is the primary site within Monsanto for the canola biotech pipeline. Current projects include increasing the value of field crops by optimizing the micronutrient and oil profile of the grain. Several genomic-based approaches are being utilized for gene discovery. Functionality of candidate genes is then assessed in model systems. Examples of the use of genomic-based approaches to identify interesting gene leads will be presented.

Monsanto provides a wide array of integrated solutions to help meet the needs of growers and commercial customers who need to control unwanted vegetation safely and effectively. Monsanto also provides products to the dairy industry to increase the efficiency of milk production, and seeds for several cropping systems.

43 Novozymes, Inc Debbie Yaver, Ph.D., Research Manager Joel Cherry, Ph.D., Research Manager, BioEnergy Group 1445 Drew Ave. Davis, CA 95616 www.novozymesbiotech.com [email protected] [email protected]

Enzymes are the natural solution to industrial problems. With enzymes we can reduce the consumption of water, energy and harmful chemicals and still make production more efficient. Novozymes is the world leader in enzyme solutions. Based on an advanced biotech platform we produce and sell more than 500 enzyme products in 120 countries. Since 1941 Novozymes has introduced almost every new industrial enzyme on the market, making us the world's largest manufacturer of enzymes today. With our minds set on innovation, we will continue to be so in the future.

Novozymes has introduced, with few exceptions, every new enzyme to the industry, from lipases, which remove grease stains during washing, to amylases, which are used to manufacture sweeteners. In our work we use the following technologies: microbiology, bioinformatics, gene technology, protein chemistry, computer chemistry, directed evolution, fermentation and recovery technology.

44 Scios, Inc. Contacts: Linda Higgins, Research Scientist Aaron Nguyen, ( DEB Graduate), Research Scientist 2450 Bayshore Parkway Mountain View, CA 94043 www.sciosinc.com [email protected] [email protected]

The overall objective of Scios' research program is to discover innovative new treatments for specific cardiorenal and inflammatory diseases and Alzheimer's disease. These disease areas are associated with substantial unmet medical needs. Scios scientists have developed an in-depth understanding of the molecular basis of these diseases and have discovered numerous product candidates, including those currently in the Scios clinical development pipeline.

The application of advanced technologies in the traditional areas of cellular and molecular biology, protein chemistry, medicinal chemistry, and pharmacology supports the ongoing discovery process. Over recent years, the Company has taken steps to develop and apply state-of-the-art platform technologies to facilitate the discovery of naturally occurring proteins and novel small molecules that can serve as potential new therapeutic agents. These technologies include genomics, combinatorial chemistry, high throughput screening and advanced models of diseases of interest. The application of these technologies has factored centrally in our success with numerous projects, like our P38-Kinase inhibitor program. In less than two years, our scientists have applied these advanced methods to identify highly potent and selective inhibitors of this key proinflammatory enzyme.

Participants

46 Retreat Participants

NIH Fellows 2005 – 2006

Suzanne (Balko) Barber Gian Oddone Chemical Engineering Chemical Engineering

Allison Dickey Jennifer Warren Chemical Engineering Civil & Environmental Engineering

Corey Dodge Chemical Engineering

Biotech Fellows 2005 - 2006

Laura Higgins Riccardo LoCascio Molecular, Cellular & Integrative Microbiology Physiology

Vannarith Leang Vu Bao Trinh Chemical Engineering Biochemistry & Molecular Biology

First Year Fellows 2005 - 2006

Dominik Green Barbara Nellis Biochemistry & Molecular Biology Chemical Engineering

Connie Jen Biochemistry & Molecular Biology

Graduate Students / Post Docs

Zachary Bent Jessica Bohonowych Microbiology Pharmacology & Toxicology

Constanze Bergt, Post-Doctoral Monica Britton Nephrology Genetics

Craig Blackmore Astra Chang Vet Med; Comparative Pathology Molecular, Cellular & Integrative Physiology

47 Victor Haroldsen Anh Phung Biochemistry & Molecular Biology Pharmacology & Toxicology

Kevin Holden Michael Plesha Microbiology Chemical Engineering & Materials Science Jessica Houghton Pharmacology & Toxicology Rowena Romano Biological & Agricultural Engineering Ting-Kuo Huang Chemical Engineering & Materials Juan Pedro Sanchez Science Plant Biology

Yi-Hwa (Patty) Hwang Erin Schwartz Biochemistry & Molecular Biology Biochemistry & Molecular Biology

Kou-San Ju David Sela Microbiology Food Science

Xianxian Liu Zane Starckewolfe Microbiology Chemistry

Ruixiao Lu Alexandre Tremeau-Bravard Statistics Molecular & Cellular Biology

Healther Palko Yuanxin (Fred) Xi Chemistry Applied Science

Li Peng He Zhu Biochemistry & Molecular Biology Biomedical Engineering

Faculty

Abhaya Dandekar Plant Sciences - Pomology Roland Faller Chemical Engineering & Materials Jason Eiserich Science Nephrology: MED Bruce Hammock Entomology & UCD Cancer Center

Karen McDonald Associate Dean, College of Engineering Chemical Engineering & Materials Alexander Revzin Science Biomedical Engineering

Davis Mills Stefan Wuertz Viticulture & Enology Civil & Environmental Engineering

Martina Newell-McGloughlin Yohei Yokobayashi UC System-wide Biotechnology Biomedical Engineering Research & Education Program Plant Pathology

Rebecca Parales Microbiology

Affiliated Companies

Douglas Banks Aubrey Jones Amgen, Inc. Novozymes, Inc.

Kristen Bennett Aaron Nguyen Monsanto, Calgene Campus Scios, Inc.

Jill Deikman Victoria Sharma Monsanto, Calgene Campus Chiron Corporation

John Donnelly Indresh Srivastava Chiron Corporation Chiron Corporation

Kenneth Gruys Henry Valentin Monsanto, Calgene Campus Monsanto, Calgene Campus

Guests

Ben Lindenmuth Douglas Kain & Dave Menshew, Penn State Faculty, Merced College

Samira Rathnayake Dallas Boehs, Billie Jo Burke, Tiffany Undergraduate, Biochemistry & Chaddock, Griselda Olivares, Linda Molecular Biology Wakentin, Sheila Worthley Students, Merced College

UC Davis Biotechnology Program Staff

Judy Kjelstrom Director

Carey Kopay Assistant Director

Marianne Hunter Event Manager

www.biotech.ucdavis.edu

The Mission of the Biotechnology Program:

The Biotechnology Program was created in 1986, to assist in the organization of university activities related to biotechnology and to coordinate such activities with other efforts on the Davis campus. It is a central facility of the Office of Research. The Program’s missions include:

• Promoting and coordinating the development of biotechnology and biotechnology - related research on the campus; • Assisting with development of new and improved facilities for biotechnology research; • Promoting research interactions between faculty and private industry and public agencies; • Recommending and implementing curriculum development and training in biotechnology; • Serving as an information and education resource on biotechnology for the campus and the public.

The Program serves as the Administrative Home for educational programs: • Designated Emphasis in Biotechnology (DEB) graduate program o www.deb.ucdavis.edu • Advanced Degree Program (ADP) for corporate employees o A PhD program for the working professional • NIH Training Program in Biomolecular Technology for PhD students • BioTech SYSTEM – K-14 educational consortium

Biotechnology Program Office:

Dr. Judith Kjelstrom - Director Carey Kopay – Assistant Director Cathy Miller – Budget Analyst Marianne Hunter – Event Manager Office location: 0301 Life Sciences Telephone: (530) 752-3260 (main line) FAX: (530) 752-4125 Email: [email protected]

NIH Training Grant in Biomolecular Technology July 1, 2002- June 30, 2007

UC Davis has been awarded a prestigious NIH training grant in biomolecular technology in recognition of the quality of multidisciplinary research and training provided by the campus. The grant is under the directorship of Bruce Hammock, Department of Entomology, and The Cancer Research Center with co-directors Karen McDonald*, Department of Chemical Engineering and Materials Science, and Associate Dean of the College of Engineering; and Martina Newell- McGloughlin, UC Systemwide Biotechnology Program, and Department of Plant Pathology. *Rosemary Smith was the original co-director from engineering, but she left campus in 2003. Karen McDonald is the current co-director from engineering.

The name, Biomolecular Technology, is chosen to reflect the emphasis of the program as an area of scientific endeavor, which is characterized by the following three elements:

1. Emphasis on the analysis of model systems of obvious significance to medicine and biotechnology; 2. The synthesis of information and research approaches from disciplines such as cellular physiology, genetics, physical biochemistry, and chemical engineering; and 3. The translation of biological information into a quantitative framework.

Through this focus the program provides well-coordinated multidisciplinary training of predoctoral graduate students in critical areas of biotechnology research and a structure for interdisciplinary research environments that integrate basic biological science and engineering disciplines as well as academic and industrial experiences. The program is designed to recruit and support trainees who show exceptional promise coupled with the drive to reach out across disciplines and forge new research directions in biotechnology.

The Faculty of the DEB have been successful in obtaining a NIH training grant within the time period of this review. The NIH Training Grant in Biomolecular Technology (1-T32-GM08799) was awarded on July 1, 2002 for 5 years. Having the formal DEB training program along with industrial internships definitely strengthened our grant proposal. Currently, there are 14 NIH biotechnology training grants funded nationwide and only three in California. UC Berkeley and Stanford have the other two grants in the State.

A question of the relationship between the DEB and the Training Program in Biomolecular Technology often arises. The answers are as follows: • The DEB is a formal training program for the NIH Training Grant. • The DEB provides training and a structure for interdisciplinary interaction, in addition to our established graduate programs. • The DEB provides a formal accreditation (on diploma & transcript) to reflect biotechnology training in cross-disciplines. • Not all the DEB students will be funded by the NIH Biotechnology Training Program. The fellows are a select subset based on a highly competitive nomination & selection process: 1. Nomination by a Faculty Trainer and completion of an application by the student. 2. Ranking by the Executive Committee of the NIH Biotechnology Training Program. It is based on: academic merit; quality of the research; interdisciplinary nature of research; and willingness to complete an internship.

Information about the NIH Biotechnology Training Grant is publicized on the DEB (www.ucdavis,edu) website.

52 NIH Training Grant Faculty

Directorship of Bruce Hammock Co-Directors are Karen McDonald and Martina Newell-McGloughlin

Gary Anderson Katherine Ferrara Animal Science Biomedical Engineering

Matthew Augustine Andrew Fisher Chemistry Chemistry

Enoch Baldwin J. Bruce German Molecular & Cellular Biology Food Science & Technology

Craig Benham Jeffrey Gregg Biomedical Engineering/Genome Center MED: Pathology

David Block Daniel Gusfield Chemical Engineering Computer Science

George Bruening Bruce Hammock Plant Pathology Entomology/UCD Cancer Center

Alan Buckpitt Alan Jackman VM: Molecular Biosciences Chemical Engineering & Materials Science Kenneth Burtis Molecular & Cellular Biology/Genome Ian Kennedy Center Mechanical & Aeronautical Engineering

Daniel Chang Tonya Kuhl Molecular & Cellular Biology Chemical Engineering & Materials Science Abhaya Dandekar Plant Sciences-Pomology Hsing-Jien Kung MED: Biochemistry/UCD Cancer Center Michael Denison Environmental Toxicology J. Clark Lagarias Molecular & Cellular Biology Bryce Falk Plant Pathology Kit Lam MED: Hematology & Roland Faller Oncology/Chemistry Chemical Engineering & Materials Science

Kent Lloyd David Rocke VM: Anatomy Physiology & Cell Applied Science Biology Simon Scott Marjorie Longo Biomedical Engineering Chemical Engineering & Materials Sciences Kate Scow Land, Air & Water Resources Karen McDonald Chemical Engineering & Materials Michael Toney Sciences Chemistry

Claude Meares Jean VanderGheynst Chemistry Biological & Agricultural Engineering

Juan Medrano Craig Warden Animal Science Neurobiology, Physiology & Behavior

Richard Michelmore David Wilson Plant Sciences – Vegetable Crops Molecular & Cellular Biology

James Murray Stefan Wuertz Animal Science/Genetic Engineering Civil & Environmental Engineering Large Animals John Yoder Atul Parikh Plant Sciences – Vegetable Crops Applied Science

Martin Privalsaky Microbiology

Robert Rice Environmental Toxicology

NIH Training Program in Biomolecular Technology

The DEB is a formal training program for the NIH Training Grant.

The DEB provides training and a structure for interdisciplinary interactions, in addition to our established graduate programs.

The DEB provides a formal accreditation (on diploma & transcript) to reflect biotechnology training in cross-disciplines.

Not all the DEB students will be part of the NIH Biotechnology Training Program. The fellows are a select subset based on a highly competitive nomination & selection process:

• Nomination by a Faculty Trainer and completion of an application by the student.

• Ranking by the Executive Committee of the Program based on academic merit, quality of the research, interdisciplinary nature of research, and a willingness to complete an internship.

Designated Emphasis in Biotechnology Program (DEB)

Goals and Mission of the DEB

The Designated Emphasis in Biotechnology (DEB) is an inter-graduate group program that allows Ph.D. students to receive and be credited for training in the area of biotechnology. The DEB provides a nurturing interactive environment to promote integration of multiple disciplinary approaches to the conduct of research and to promote learning in biotechnology. The mission is to prepare well-educated students to approach problems with creativity and flexibility. The program will provide tools for the students to be leaders, visionaries, entrepreneurs, researchers and teachers in the broad area of biomolecular technology.

DEB Mission:

To provide well-coordinated, cross-disciplinary training of graduate students in critical areas of biomolecular technology research.

To promote interdisciplinary research environments that integrate basic biological science, engineering and computational disciplines.

To allow cross-disciplinary training and trainee experience in a biotechnology company or cross-college laboratory.

Students come from a wide array of disciplines: Participating graduate programs currently include 23 programs: Agricultural and Environmental Chemistry; Biochemistry and Molecular Biology; Biological Systems Engineering (formerly Biological & Agricultural Engineering); Biomedical Engineering; Biophysics; Cell & Developmental Biology; Chemical Engineering; Chemistry; Civil and Environmental Engineering; Comparative Pathology; Entomology; Genetics; Immunology; Materials Science and Engineering; Mechanical and Aeronautical Engineering; Food Science; Microbiology ; Molecular, Cellular and Integrative Physiology (formerly Physiology); Nutrition; Pharmacology & Toxicology; Plant Biology; Plant Pathology; and Statistics. The DEB program supplements a student's Ph.D. curriculum and those completing the program will obtain an official designation on their diploma & transcript indicating a qualification in biotechnology. Example: Doctoral Degree in Microbiology with a Designated Emphasis in Biotechnology

Brief History:

The DEB was formally established in 1997 as an outgrowth of the first NIH Training Grant in Biotechnology (funded in the early 1990s). The DEB became the formal training program for the current NIH Training Grant in Biomolecular Technology (1-T32- GM08799: July 1, 2002-June 30, 2007). The DEB provides a very effective multidisciplinary biotechnology concentration, which includes exposure to bioethics, business and legal aspects of biotechnology as well as a 3-6 month internship in a biotechnology company or research laboratory in another college or national laboratory. As of December 2003, the DEB has 23 affiliated graduate groups or departmentally based graduate programs and we are in the process of adding Biostatistics and Electrical & Computer Engineering. The number of students in the Designated Emphasis in Biotechnology has increased dramatically over the last two years and now boasts over 50 members, with many being first year students. We have graduated 14 students with a DEB notation on their diplomas as of December of 2003.

Program Administration:

The administrative home for the DEB and the NIH Training Grant in Biomolecular Technology is the UC Davis Biotechnology Program. Dr. Judith Kjelstrom serves as the DEB and NIH Training Grant program coordinator for the DEB, in addition to directing the Biotechnology Program. She works closely with the DEB chair, Abhaya Dandekar (Department of Pomology) and the rest of the executive committee: Karen McDonald (Chemical Engineering and Materials Science), Robert Rice (Environmental Toxicology) and David Rocke (Applied Science/Biostatistics) to oversee the day-to-day activities of the graduate program.

Course Work:

The DEB has a required core curriculum for students regardless of whether their graduate major is in biological science, engineering, statistics, etc. A key feature of the DEB is its requirement for a research internship at a cooperating biotechnology company or a cross- college site. When the students complete their Ph.D. requirements as well as the DEB requirements, their diploma notes not only their graduate major, but also that they have completed the DEB (e.g., "Ph.D. in Chemical Engineering with a Designated Emphasis in Biotechnology"). We have created a website for the Designated Emphasis in Biotechnology (http://www.deb.ucdavis.edu/) to advertise the program as well as the NIH Training Grant. The announcement of the grant is on the site. Program information, forms, pictures and other pertinent information is listed on the site. We have linked the website to graduate home pages of most of the 23 DEB program affiliates in the Division of Biological Sciences, College of Engineering, College of Letters and Science and the College of Agriculture and Environmental Sciences.

1. Course Requirements: a. MCB 263 (2 units): Biotechnology Fundamentals and Application (winter quarter, alternate odd numbered years) An interdisciplinary course which includes: introduction to modern recombinant DNA technology; rate processes of biological systems, optimization of bioreactor performance; practical issues in biotechnology; and some specific case studies of the development of biotechnology products and processes. Grading: Letter grade; two one-hour exams, one research paper (team project) on a selected topic relevant to biotechnology, and regular reading assignments. b. MCB 282 (variable): Biotechnology Internship (may be done any quarter) The internship will expose qualified graduate students to research activities in a biotechnology company, to company culture, to legal and business aspects of industry, and to another career option. A minimum of 3 months internship at a local biotechnology company or cross college or national laboratory (i.e. Lawrence Berkeley Laboratory, Lawrence Livermore National Laboratory, etc.). S/U grading; research performance (student report) will be evaluated by the professor in charge and in consultation with the company trainer. c. MCB/ECH 294 (1 unit): Current Progress in Biotechnology (fall, winter and spring quarters). Three quarters of seminar are required for the DEB Program. This course is an interdisciplinary seminar, featuring speakers from industry as well as academia. The students will have an opportunity to discuss the seminar topic with the lecturers, to learn about biotechnology research activities at companies and to network with speaker. Grading: S/U grading, attendance is required, and a summary report on the seminars is required at the end of the quarter. d. MIC 292 (1 unit): From Discovery to Product - An Introduction to Biotechnology at the Industrial Level. (winter quarter; even numbered years). MIC 292 is an approved seminar elective for the DEB program (may substitute for one quarter of MCB/ECH 294). This course is designed to provide a unique opportunity to gain insight into basic and applied biotechnology at the industrial level. Lectures are presented by senior scientists from Novozymes Biotech, Inc. in Davis California (http://www.novozymesbiotech.com/). A tour of the industrial facilities will be arranged. Grading: S/U grading, attendance is required, and a summary report on the seminars is required at the end of the quarter. e. GGG 296 (2 units): Scientific Professionalism and Integrity (fall quarter) The course will allow the student to become familiar with their roles and responsibilities as a professional scientist and/or instructor. While some standards of acceptable scientific behavior will be presented in class, most of the time will be spent discussing various "gray zone" scenarios, in which proper conduct is unclear. Grading: S/U grading; active class participation in class discussions is required. This course is currently highly recommended, but will be required, pending approval.

2. Qualifying Exam Requirements: The Ph.D. qualifying exam should demonstrate appropriate knowledge with the area of biotechnology. At least one faculty member of the designated emphasis shall participate in the qualifying examination.

3. Thesis Requirements: The dissertation committee shall include at least one faculty member of the designated emphasis. The major professor must be a participating DEB member.

4. Additional Requirements: Regular attendance at the annual Biotechnology Training retreat and at the informal Pizza Chalk Talk Seminars (talks by students and faculty on current research) is expected.

59 DEB Program Students as of March 2006

Tian Bao Ying Chen Chemical Engineering Statistics

Suzanne (Balko) Barber Li-Kuan (Alex) Chen Chemical Engineering Biomedical Engineering

Jason Bell Jerome Diaz Biochemistry & Molecular Biology Food Science

Sandra Bennun Serrano Allison Dickey Chemical Engineering Chemical Engineering

Zachary Bent Kevin Dietzel Food Science Microbiology

Susanne (Kuhlman) Berglund Corey Dodge Microbiology Chemical Engineering

Craig Blackmore Amanda Enstrom Comparative Pathology Immunology

Craig Blanchette James Evans Biophysics Biochemistry & Molecular Biology

Jessica Bohonowych Wen-Ying Feng Environmental & Toxicology Statistics (Biostatistics Emphasis)

Jerry Boonyaratanakornkit Robin GrayMerod Biochemistry & Molecular Biology Civil & Environmental Engineering

Monica Britton Dominik Green Genetics Biochemistry & Molecular Biology

Tim Cao Moraima Guadalupe Biomedical Engineering Comparative Pathology

Astra Cartier Victor Haroldsen Plant Biology Biochemistry & Molecular Biology

Shannon Ceballos Laura Higgins Molecular & Cellular Biology Molecular, Cellular & Integrative Physiology Honglin Chen Genetics

60 Kevin Holden Ruixiao Lu Microbiology Statistics

Jennifer Horner Thomas Luu Biochemistry & Molecular Biology Biochemistry & Molecular Biology

Jessica Houghton Caroline Meloty-Kapella Pharmacology & Toxicology Cell & Developmental Biology

Ting-Kuo Huang Brad Niles Chemical Engineering Nutrition

Yi-Hwa (Patty) Hwang Gian Odonne Biochemistry & Molecular Biology Chemical Engineering

Aminah Ikner Li Peng Biochemistry & Molecular Biology Biochemistry & Molecular Biology

Connie Jen Ying Peng Biochemistry & Molecular Biology Genetics

Kou-San Ju Anh Phung Microbiology Biochemistry & Molecular Biology

Michael Kareta Warren Place Biochemistry & Molecular Biology Microbiology

Pinar Kocabas Michael Plesha Chemical Engineering Chemical Engineering

Pavan Kumar Wade Reh Plant Biology Genetics

Nathaniel Leachman Rowena Romano Cell & Developmental Biology Biological Systems Engineering

Vannarith Leang Ahmad Rushdi Chemical Engineering Electrical & Computer Engineering

Young (Lauren) Lee Juan Pedro Sanchez Biochemistry & Molecular Biology Plant Biology

Xianxian (Janice) Liu Erin Schwartz Microbiology Biochemistry & Molecular Biology

Riccardo LoCascio Andres Schwember Microbiology Plant Biology

61 Daniel Scott Jared Townsend Chemistry Biochemistry & Molecular Biology

David Sela Vu Trinh Food Science Biochemistry & Molecular Biology

Jillian Silva Jennifer Warren Biochemistry & Molecular Biology Civil & Environmental Engineering

Samir Singh Andrew Wong Chemical Engineering Genetics

Cheng Song Scott Wong Cell & Developmental Biology Biochemistry & Molecular Biology

Zane Starkewolfe Chun-Yi (Jimmy) Wu Chemistry Pharmacology & Toxicology

James Stice Yuanxin (Fred) Xi Molecular, Cellular & Integrative Applied Science Physiology Liang Yang Wesley Sughrue Biochemistry & Molecular Biology Biochemistry & Molecular Biology Kseniya Zakharyevich Qi Sun Microbiology Chemical Engineering Melinda Zaragoza Alan Szmodis Microbiology Biophysics He (James) Zhu Esra Talu Biomedical Engineering Chemical Engineering Erin Zumstein Jennifer Taylor Biochemistry & Molecular Biology Comparative Pathology

DEB Faculty Participants

Agricultural & Pam Ronald John H. Crowe Environmental Chemistry Robert Rucker Thorsten Dieckmann Linda Bisson Dewey Ryu Roland Faller Andrew Clifford Earl Sawai Andrew Fisher Michael Denison Kazuhiro Shiozaki Ching Yao Fong J. Bruce German Steven Theg Thomas Jue Bruce Hammock Valerie Williamson Stephen Kowalczykowski You-Lo Hsieh David Wilson Tonya Kuhl Fumio Matsumura Reen Wu Janine LaSalle Krishnan Nambiar John Yoder Marjorie Longo Kate Scow Glenn Young Atul Parikh Scott I. Simon Biochemistry & Molecular Biological Systems EngineeringHenning Stallberg Biology (formerly "Biological & Steven Theg Steffen Abel Agricultural Engineering") Michael D. Toney Everett Bandman David Slaughter David Wilson Alan Bennett Jean VanderGheynst Yin Yeh Linda Bisson Ruihong Zhang Sue Bodine Cell & Developmental Biology Sean Burgess Biomedical Engineering Gary Anderson R. Holland Cheng Abdul Barakat Everett Bandman Ronald Chuang Craig Benham Ron Baskin Gino Cortopassi Roland Faller Frederic Chedin Michael Denison Katherine Ferrara Jason Eiserich Peggy Farnham Ian Kennedy Peggy Farnham Charles Gasser Tonya Kuhl Paul FitzGerald Bruce Hammock Kit Lam Anne Knowlton Kentaro Inoue Marjorie Longo Su-Ju Lin Thomas Jue Angelique Louie Bo Liu Clarence Kado Claude Meares Robert Rice Dan Kliebenstein Atul Parikh Alice Tarantal Stephen Kowalczykowski Alexander Revzin Richard Tucker Hsing-Jien Kung Dewey Ryu Reen Wu J. Clark Lagarias Scott Simon Kit Lam Pieter Stroeve Chemical Engineering & Janine LaSalle Alice Tarantal Materials Science Engineering Su-Ju Lin Yohei Yokobayashi David Block Paul Luciw Stephanie Dungan Claude Meares Biophysics Nael El-Farra Jerry Powell Abdul Barakat Roland Faller Marty Privalsky Craig Benham Tonya Kuhl Robert Rice R. Holland Cheng

63 Marjorie Longo David Block Immunology Karen McDonald Christine Bruhn Satya Dandekar Ron Phillips Stephanie Dungan Kit Lam Robert Powell Oliver Fiehn Jose Torres Dewey Ryu J. Bruce German Tilahun Yilma Pieter Stroeve David Mills Krishnan Nambiar Material Science & Chemistry Robert Powell Engineering Matthew Augustine David Reid Subhash Risbud Alan Balch Dewey Ryu Thorsten Dieckman Glenn Young Mechanical & Aeronautical Andrew Fisher Engineering Bruce Hammock Genetics Abdul Barakat J. Clark Lagarias Steffan Abel Ian Kennedy Carlito Lebrilla Alan Bennett Claude Meares Linda Bisson Microbiology Krishnan Nambiar George Bruening Stephen Barthold Michael Toney Sean Burgess Blaine Beaman Frederic Chedin Linda Bisson Civil & Environmental Douglas Cook Richard Bostock Engineering Gino Cortopassi George Bruening Daniel Chang Abhaya Dandekar Sean Burgess Stefan Wuertz Bryce Falk R. Holland Cheng Peggy Farnham Ronald Chuang Comparative Pathology Charles Gasser Satya Dandekar Peter Barry David Gilchrist Bruce Hammock Stephen Barthold Tom Gradziel Clarence Kado Satya Dandekar Paul Gumerlock Stephen Kowalczykowski Jeff Gregg Stacy Harmer Su-Ju Lin Rivkah Isseroff Clarence Kado Paul Luciw Kit Lam Dan Kliebenstein Karen McDonald Thomas North Stephen Kowalczykowski David Mills Jerry Powell Janine LaSalle David Ogrydziak Earl Sawai Su-Ju Lin Rebecca Parales Jay Solnick Juan Medrano Marty Privalsky Alice Tarantal Richard Michelmore Dewey Ryu Jose Torres James Murray Earl Sawai Reen Wu Marty Privalsky Kate Scow Tilahun Yilma Pam Ronald Kazuhiro Shiozaki Earl Sawai Jay Solnick Entomology Alison Van Eenennaam Jose Torres Bruce Hammock Valerie Williamson Tilahun Yilma Food Science Reen Wu Glenn Young Diane Barrett John Yoder Linda Bisson

64 Molecular, Cellular and Jason Eiserich Dan Kliebenstein Integrative Physiology Bruce Hammock J. Clark Lagarias (formerly "Physiology") Anne Knowlton Bo Liu Gary Anderson Hsing-Jien Kung Terence Murphy Sue Bodine Jerold Last Michael Reid Christopher Calvert Fumio Matsumura Pam Ronald Nipavan Chiamvimonvat Robert Rice Valerie Williamson Jason Eiserich Robert Rucker John Yoder Anne Knowlton Barry Wilson John Rutledge Reen Wu Plant Pathology Dewey Ryu Richard Bostock Judith Stern Plant Biology George Bruening Alice Tarantal Steffen Able Douglas Cook Barry Wilson Diane Barrett Bryce Falk Reen Wu Alan Bennett David Gilchrist Richard Bostock Clarence Kado Nutritional Biology Kent Bradford Richard Michelmore Christopher Calvert Douglas Cook Pam Ronald Andrew Clifford Abhaya Dandekar Steven Theg J. Bruce German Katayoon "Katy" Dehesh Judith Stern Don Durzan Statistics Bryce Falk Andrew Clifford Pharmacology & Toxicology Charles Gasser Shu Geng Ronald Chuang Tom Gradziel Katherine Pollard Gino Cortopassi Stacy Harmer David Rocke Michael Denison Kentaro Inoue

The Value of Internships

Over the last 13 years (even before the formal DEB program was established), we have placed pre-doctoral students in a variety of biotechnology companies for their industrial research experience. They include:

Agilent Technologies Alza Amgen Bayer Berlex Biosciences Celera AgGen Chiron DuPont Exelixis Genentech ICOS Maxygen Monsanto, Calgene Campus; Novozymes Biotech Scios Syntex Recovery Sciences Roche Biosciences Ventria Biosciences and others

Industry Partners gain many things from internships: • Access to highly talented creative researchers • Opportunity to gain inside tract on future employees • Through students, further collaboration with scientists on campus • Participate in the annual retreat to meet UC scientists students, potential interns, other company scientists • Potential to use UC facilities through the collaboration • Opportunity to participate in weekly campus seminars

Students gain much from internships: • Ability to work in a highly creative non-academic environment • Opportunity to participate in focused team approach to defined research goals • Ability to use equipment and facilities not available on campus • Discover the type of environment, which suits future career goals • Participate in industry seminars • Enhanced curriculum vitae: reference letters and new skills • Access to potential employment opportunities

Currently, there are 86 students enrolled, so we need more Academic- Industry Partnerships