When model organisms are exposed to chemicals, resulting mutagenesis can provide insights on the chemical’s genotoxicity, which is an indicator of the chemical’s potential to cause cancer or birth defects. In fact, direct mutagenesis assays in bacteria are one of the three assays required by regulatory agencies for demonstrating the safety of potential clinical compounds. Mutagenesis assays are also used to study various DNA processes, such as replication, repair, damage tolerization, and homeostasis.

Researchers at the University of California, Davis have developed a method to stop bacterial growth while maintaining desirable metabolic functions for therapeutic and biotechnological applications.

Researchers at UC Berkeley have developed a machine learning model that can aide in the design of more efficient viral vector libraries.Directed evolution of biomolecules to generate large numbers of randomized variants is an important innovation in biochemistry. This methodology can be applied to myriad biomolecules of interest, including viruses. In the case of viral variants, this method may be used to select viral variants or viral vectors with specific properties such as tissue type specificity, increased replication capacity, or enhanced evasion of the immune system. However, testing large numbers of viral variants for specific properties is inherently time consuming and limits potential innovation.The inventors have devised a new method to optimize the functionality of viral libraries with many random variants. Specifically, this methodology comprises a machine learning model that systematically designs more effectively starting libraries by optimizing for a chosen factor. This method works by using a training set of viruses that can be evaluated experimentally for the chosen optimization factor (e.g., packaging efficiency, infectivity of a cell line, etc.). These experiments will then provide a fitness value for each viral variant, and the fitness value matched with viral variant sequences will in turn be used in a supervised machine learning model to select sequences for a larger library that is optimized for the chosen factor.

Researchers at the University of California, Davis have developed a viral amplicon-based vector system for heterologous protein expression and production in plants.

Current methods for ribonucleic acid (RNA) delivery are inefficient and toxic. UCI researchers have synthesized a new delivery system that is not only efficient and non-toxic but also allows the delivery of RNAs of multiple shapes and sizes.

UCLA researchers in the Department of Medicine and the Department of Surgery have developed a novel lentiviral vector that expresses a codon-optimized sequence of a T cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1 as well as a positron emission tomography (PET) reporter and suicide gene HSV1-sr39tk for use in adoptive T cell therapy for cancer treatment.

Researchers at the University of California, Davis have cultured a titi monkey adenovirus (TMAdV,) and used the virus to develop a model of human respiratory disease.

Echo Particle Image Velocimetry (PIV) is a non-invasive ultrasonic technique used to image blood flow in patients. Particles that may be used as flow tracers with PIV include currently FDA approved contrast agents. Currently, 2D blood flow information obtained by echocardiography is widely used to diagnose cardiac dysfunction. While this 2D echocardiography method is useful, it does not provide sufficient accuracy for characterizing complex 3D flows in the heart. For example, it is difficult to accurately image flow patterns in the right heart or hearts of patients with congenital defects or quantify mitral regurgitation. Researchers at the University of California, Irvine have developed a new method for multi-planar 3D reconstruction of 2D Echo Particle Image Velocimetry (PIV) data. This method may be used to image and assess blood flows from the heart chambers in real-time therefore allowing 4D imaging of blood flows in the heart.

Dr. Benhur Lee and colleagues in the UCLA Department of Microbiology, Immunology and Molecular Genetics have developed a novel system to detect and characterize HIV with unprecedented sensitivity and rapidity.  

Brief description not available

Eukaryotic promoters are regulated by a combination of sequence-specific DNA-binding proteins, general transcription initiation factors, and associated accessory factors. The sequence-specific transcription factors can be divided into several classes on the basis of the activation domains they posess. This disclosure relates to several Human cDNA clones and/or expression vectors encoding c-jun, AP2, SP1, and CTF/NF1 TAF genes. Reference; B.D. Dynlacht, et al., Isolation of Coactivators Associated with the TATA-Binding Protein That Mediate Transcriptional Activation. 1991. Cell 66:563-76

In Drosophila and human cells, the TATA binding protein (TBP) of the transcription factor IID (TFIID) complex is tightly associated with multiple subunits termed TBP-associated factors (TAFs) that are essential for mediating regulation of RNA polymerase II transcription. This diclosure makes available various cDNA expression clones encoding dTAFs 250, 150, 110, 80,60,40,30, and 30B (in vitro translation vectors) from Drosophila. References; C.P. Verrijzer, et al., Drosophila TAFII150: similarity to Yeast Gene TSM-1 and Specific Binding to Core Promoter DNA. 1994. Science 264:933-41 T. Hoey, et al., Molecular Cloning and Functional Analysis of Drosophila TAF110 Reveal Properties Expected of Coactivators. 1993. Cell 72; 247-60

Radio antennas must maintain their paraboloid shape and directional positioning in order to work properly. However wind can load the antenna dish and cause it to lose its shape and position. To address this situation, researchers at UC Berkeley have developed a support system that strengthens antenna dishes and provides several structural enhancements. The support system consists of reinforcements that enable firm radial and torsional support as well as an optimal amount of axial flexibility and support. This design allows for a large open area so that azimuth and elevation-bearing systems can be positioned near to the reflector vertex. This positioning enables lower loads and less structural requirements for the pedestal and drives.

Log-periodic antennas are capable of transmitting and receiving signals across a large bandwidth. However, their bandwidth range can be too large for the entire signal to be simultaneously digitized. To address this issue, researchers at UC Berkeley have developed an innovative feed for broadband antennas. This feed converts the broadband radio signals such that they can be more readily digitized and processed.

Scientists at the University of California Berkeley have designed FRET sensor of a complex of Ran-GTP-importin b that is a fluorescent protein construct consisting of Importin b-domain (IBB) of importin a flanked by fluorescent proteins (donor and acceptor) capable of FRET. The sensor functions as an indirect sensor of Ran-GTP through its Ran-GTP sensitive specific interaction with importin b. See: P. Kalab, Weis, K., and Heald, R. (2002), Visualization of a Ran-GTP Gradient in Interphase and Mitotic Xenopus Egg Extracts. Science, March 29, 2002, Vol. 295, 2452-2456. The small guanosine triphosphate Ran is loaded with guanosine tripohosphate (GTP) by the chromatin bound guanine nucleotide exchange factor RCC1 and releases import cargoes in the nucleus during interphase. In mitosis, Ran-GTP promotes spindle assembly around the chromosomes by locally discharging cargoes that regulate microtubule dynamics and organization. We used fluorescence energy transfer-based biosensors to visualize gradients of Ran-GTP and liberated cargoes around chromosomes in mitotic Xenopus egg extacts. Both gradients were required to assemble and maintain spindle structure. During interphase, Ran-GTP was highly enriched in the nucleoplasm, and a steep concentration difference between nuclear and cytoplasmic Ran-GTP was established, providing evidence for a Ran-GTP gradient surrounding chromosomes throughout the cell cycle.

Scientists at the University of California Berkeley have designed FRET-based sensor of Ran-GTP that is a fluorescent protein construct consisting of Ran binding domain flanked by fluorescent proteins (donor and acceptor) capable of FRET. The sensor functions as: 1) a direct sensor of Ran-GTP, and 2) an indirect sensor of Ran-GTP-binding proteins such as importin-b family proteins. See: P. Kalab, Weis, K., and Heald, R. (2002), Visualization of a Ran-GTP Gradient in Interphase and Mitotic Xenopus Egg Extracts. Science, March 29, 2002, Vol. 295, 2452-2456. The small guanosine triphosphate Ran is loaded with guanosine tripohosphate (GTP) by the chromatin bound guanine nucleotide exchange factor RCC1 and releases import cargoes in the nucleus during interphase. In mitosis, Ran-GTP promotes spindle assembly around the chromosomes by locally discharging cargoes that regulate microtubule dynamics and organization. We used fluorescence energy transfer-based biosensors to visualize gradients of Ran-GTP and liberated cargoes around chromosomes in mitotic Xenopus egg extacts. Both gradients were required to assemble and maintain spindle structure. During interphase, Ran-GTP was highly enriched in the nucleoplasm, and a steep concentration difference between nuclear and cytoplasmic Ran-GTP was established, providing evidence for a Ran-GTP gradient surrounding chromosomes throughout the cell cycle.

This invention makes available plasmids designed to express derivatives of Saccharomyces cerevisiae Ste5 protein tagged with an N-terminal in-frame (His)6 tract and a c-Myc epitope recognized by the monoclonal antibody, 9E10, and /or fused in-frame at either its N- or C-terminus to the Aequoria victoria Green Fluorescent Protein (GFP), or mutant derivatives of Ste5 in these contexts. References: Hasson et al. 1994. Mol. Cell Biol. 14:1054-65 Inouye et al. 1997. Science 278:103-6 Inouye et al. 1997. Genetics 147:479-92 Sette et al. 2000. Mol Biol. Cell 11:4033-49 Bardwell et al. 2001. J. Biol. Chem. 276:10374-86 Kunzler et al. 2001. Genetics 157:1089-105

Listeria monocytogenes is a non-spore-forming, opportunistic Gram-positive pathogen, responsible for severe infections in both animals and humans. Recurrent outbreaks of Listeriosis have emphasized the need for better understanding of the molecular pathogenicity mechanisms and the interaction of the organism and specific bacteriophages. Investigators at University of California, Berkeley have made an integration vector carrying the integrase and attachment site of phage A118. References: Loessner et al. 2000. Mol. Microbiology 35:324-40. Fleming et al. 1985. New Eng. J. Med. 312:404-7

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus infecting more than 75% of the U.S population. It is a leading cause of birth defects in newborns, a major cause of morbidity and mortality in immunocompromised individuals, such as transplant recipients and patients with AIDS, and even in healthy adults, this virus causes a life-long subclinical infection that may be associated with the development of atherosclerosis. Study of murine cytomegalovirus (MCMV) serves as a model for understanding of HCMV- associated diseases. The reagents covered in this invention include (1) MCMV mutant (RvM78) that contained a mutation at viral open reading frame M78, (2) an expression plasmid construct (pM78-FLAG) that contains M78 coding sequence driven by an eukaryotic expression cassette, and (3) a mouse 3T3 cell line that contains pM78-Flag and expresses M78 protein. References: Zhan et al. 2000 Virology 266:264-74. Zhan et al. 2000 J. Virology 74:7411-21

Minor histocompatibility (H) antigens elicit T cell responses and thereby cause chronic graft rejection and graft-vs.-host disease among MHC identical individuals. Although numerous independent H loci exist in mice of a given MHC haplotype, certain H antigens dominate the immune response and are thus of considerable conceptual and therapeutic importance. The H60 gene was isolated as a cDNA clone from the mouse strain BALB.B. This gene contains an antigenic peptide that elicits a strong cytotoxic T cell response when C57BL/6 mice are immunized with BALB.B spleen cells. References: Malarkannan et al. 1998. J Immunol. 161:3501-9. Karttunen et al. 1992. PNAS 89:6020-4.

To assay transcription from promoters under the control of Filamentous Response Elements (FREs) which comprise binding sites for the transcription factors Ste7 and Tec1, investigators at UCB constructed a plasmid (YEpU-FTyZ) in which expression of the E. coli lacZ gene is driven by the FRE of the transposon Ty1. Reference; Cook et al. 1997 Nature 390:85-8.

Apoptosis is a phenomenon observed during development of many cell types in many organisms. It is an internal, programmed cell death characterized by DNA fragmentation into nucleosome-size pieces. Anti-CD3-induced apoptosis in T-cell hybridomas and immature thymocytes requires new gene transcription and may be related to negative selection during T-cell development. Using subtractive hybridization, we isolated a complementary DNA clone encoding the orphan steroid receptor Nur77 (refs 7-9). It shows different patterns of messenger RNA induction between apoptotic and stimulated T cells. We report here the use of gel shift analysis to demonstrate that the Nur77 protein is present at high levels in apoptotic T-cell hybridomas and apoptotic thymocytes, but not in growing T cells or stimulated splenocytes. A Nur77 dominant negative protected T-cell hybridomas from activation-induced apoptosis. Hence Nur77 is necessary for induced apoptosis in T-cell hybridomas. Reference: Woronicz, J, et al., 1994 Nature 367:277-81

Plasmid vectors (pV-alpha-11-GH and pLCRc) have been developed for the expression of transgenic proteins in immature and mature T cells. Research using these vectors has been published: Diaz et al. Immunity 1:207 (1994) Ortiz et al. EMBO J. 16:5037 (1997) Kabra et al. J. Immunol. 162:2766 (1999)