Genomes and Genes
Summary: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc.
Publications259 found, 100 shown here
- Enzymatic assembly of DNA molecules up to several hundred kilobasesDaniel G Gibson
The J Craig Venter Institute, Synthetic Biology Group, Rockville, Maryland, USA
Nat Methods 6:343-5. 2009..This assembly method can be used to seamlessly construct synthetic and natural genes, genetic pathways and entire genomes, and could be a useful molecular engineering tool...
- Genetic engineering of human pluripotent cells using TALE nucleasesDirk Hockemeyer
The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA
Nat Biotechnol 29:731-4. 2011Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases...
- Simple and highly efficient BAC recombineering using galK selectionSøren Warming
Mouse Cancer Genetics Program, National Cancer Institute Frederick, MD 21702 1201, USA
Nucleic Acids Res 33:e36. 2005....
- Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleasesElena E Perez
Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, 421 Curie Blvd, Room 554, BRB II III, Philadelphia, Pennsylvania 19104 6160, USA
Nat Biotechnol 26:808-16. 2008..Thus adoptive transfer of ex vivo expanded CCR5 ZFN-modified autologous CD4(+) T cells in HIV patients is an attractive approach for the treatment of HIV-1 infection...
- Creation of a bacterial cell controlled by a chemically synthesized genomeDaniel G Gibson
The J Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA
Science 329:52-6. 2010..The new cells have expected phenotypic properties and are capable of continuous self-replication...
- Harnessing homologous recombination in vitro to generate recombinant DNA via SLICMamie Z Li
Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Nat Methods 4:251-6. 2007..This flexibility allows much greater versatility in the generation of recombinant DNA for the purposes of synthetic biology...
- Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coliParayil Kumaran Ajikumar
Department of Chemical Engineering, Massachusetts Institute of Technology MIT, Cambridge, MA 02139, USA
Science 330:70-4. 2010..More broadly, the modular pathway engineering approach helped to unlock the potential of the MEP pathway for the engineered production of terpenoid natural products...
- Automated design of synthetic ribosome binding sites to control protein expressionHoward M Salis
Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, USA
Nat Biotechnol 27:946-50. 2009..The proposed forward engineering approach should accelerate the construction and systematic optimization of large genetic systems...
- Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleasesYannick Doyon
Sangamo BioSciences, Inc, Pt Richmond Tech Center, 501 Canal Blvd, Suite A100, Richmond, California 94804, USA
Nat Biotechnol 26:702-8. 2008..The frequency and precision of gene-disruption events observed suggest that this approach should be applicable to any loci in zebrafish or in other organisms that allow mRNA delivery into the fertilized egg...
- Targeted gene inactivation in zebrafish using engineered zinc-finger nucleasesXiangdong Meng
Program in Gene Function and Expression, University of Massachusetts Medical School, Lazare Research Building, 6th Floor, 364 Plantation St, Worcester, Massachusetts 01605, USA
Nat Biotechnol 26:695-701. 2008..The use of engineered ZFNs to introduce heritable mutations into a genome obviates the need for embryonic stem cell lines and should be applicable to most animal species for which early-stage embryos are easily accessible...
- Consolidated bioprocessing of cellulosic biomass: an updateLee R Lynd
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755, USA
Curr Opin Biotechnol 16:577-83. 2005..Recent studies of the fundamental principles of microbial cellulose utilization support the feasibility of CBP...
- An efficient recombination system for chromosome engineering in Escherichia coliD Yu
Gene Regulation and Chromosome Biology Laboratory and Mouse Cancer Genetics Program, National Cancer Institute, Division of Basic Science, National Cancer Institute Frederick Cancer Research and Development Center, Frederick, MD 21702, USA
Proc Natl Acad Sci U S A 97:5978-83. 2000..This system will be especially useful for the engineering of large bacterial plasmids such as those from bacterial artificial chromosome libraries...
- Refinement and standardization of synthetic biological parts and devicesBarry Canton
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, 68 580, Cambridge, Massachusetts 02139, USA
Nat Biotechnol 26:787-93. 2008..The process of refinement and characterization leading to the BBa_F2620 datasheet may serve as a starting template for producing many standardized genetically encoded objects...
- Production of the antimalarial drug precursor artemisinic acid in engineered yeastDae Kyun Ro
California Institute of Quantitative Biomedical Research, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA
Nature 440:940-3. 2006..annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices...
- Precise manipulation of chromosomes in vivo enables genome-wide codon replacementFarren J Isaacs
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Science 333:348-53. 2011..Our methods treat the chromosome as both an editable and an evolvable template, permitting the exploration of vast genetic landscapes...
- Plant responses to drought, salinity and extreme temperatures: towards genetic engineering for stress toleranceWangxia Wang
The Robert H Smith Institute of Plant Sciences and Genetics in Agriculture, and the Otto Warburg Center for Agricultural Biotechnology, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
Planta 218:1-14. 2003..The review examines the following aspects: regulatory controls, metabolite engineering, ion transport, antioxidants and detoxification, late embryogenesis abundant (LEA) and heat-shock proteins...
- A highly efficient recombineering-based method for generating conditional knockout mutationsPentao Liu
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA
Genome Res 13:476-84. 2003..This method should also facilitate the generation of knock-in mutations and transgene constructs, as well as expedite the analysis of regulatory elements and functional domains in or near genes...
- Non-fermentative pathways for synthesis of branched-chain higher alcohols as biofuelsShota Atsumi
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, California 90095, USA
Nature 451:86-9. 2008..In particular, we have achieved high-yield, high-specificity production of isobutanol from glucose. The strategy enables the exploration of biofuels beyond those naturally accumulated to high quantities in microbial fermentation...
- Rapid "open-source" engineering of customized zinc-finger nucleases for highly efficient gene modificationMorgan L Maeder
Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA
Mol Cell 31:294-301. 2008..In summary, OPEN provides an "open-source" method for rapidly engineering highly active zinc-finger arrays, thereby enabling broader practice, development, and application of ZFN technology for biological research and gene therapy...
- Microbial production of fatty-acid-derived fuels and chemicals from plant biomassEric J Steen
Joint BioEnergy Institute, Emeryville, California 94608, USA
Nature 463:559-62. 2010..Furthermore, we show engineering of the biodiesel-producing cells to express hemicellulases, a step towards producing these compounds directly from hemicellulose, a major component of plant-derived biomass...
- TALEN-mediated precise genome modification by homologous recombination in zebrafishYao Zu
Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing, China
Nat Methods 10:329-31. 2013..We also successfully targeted two additional genes. Homologous recombination in zebrafish with a dsDNA donor expands the utility of this model organism...
- Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector deliveryAngelo Lombardo
San Raffaele Telethon Institute for Gene Therapy, Via Olgettina, 58, 20132 Milan, Italy
Nat Biotechnol 25:1298-306. 2007....
- A phage integrase directs efficient site-specific integration in human cellsA C Groth
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305 5120, USA
Proc Natl Acad Sci U S A 97:5995-6000. 2000..These observations form the basis for site-specific integration strategies potentially useful in a broad range of genetic engineering applications.
- Recombineering: a homologous recombination-based method of genetic engineeringShyam K Sharan
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
Nat Protoc 4:206-23. 2009Recombineering is an efficient method of in vivo genetic engineering applicable to chromosomal as well as episomal replicons in Escherichia coli. This method circumvents the need for most standard in vitro cloning techniques...
- Synthetic biology moving into the clinicWarren C Ruder
Howard Hughes Medical Institute, Department of Biomedical Engineering, and Center for Biodynamics, Boston University, Boston, MA 02115, USA
Science 333:1248-52. 2011..Here, we highlight advances in the biomedical application of synthetic biology and discuss the field's clinical potential...
- Challenges in engineering microbes for biofuels productionGregory Stephanopoulos
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Science 315:801-4. 2007..There is justified optimism that the full potential of biofuel production from cellulosic biomass will be obtainable in the next 10 to 15 years...
- Emergent properties of reduced-genome Escherichia coliGyörgy Pósfai
Institute of Biochemistry, Biological Research Center, H 6726 Szeged, Hungary
Science 312:1044-6. 2006..Eradication of stress-induced transposition evidently stabilized the MDS genomes and provided some of the new properties...
- Unexpected failure rates for modular assembly of engineered zinc fingersCherie L Ramirez
Nat Methods 5:374-5. 2008
- Targeted chromosomal deletions in human cells using zinc finger nucleasesHyung Joo Lee
Department of Chemistry, Seoul National University, Seoul, South Korea
Genome Res 20:81-9. 2010..Thus, ZFN-induced genomic deletions should be broadly useful as a novel method in biomedical research, biotechnology, and gene therapy...
- Homing endonucleases: from microbial genetic invaders to reagents for targeted DNA modificationBarry L Stoddard
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, A3 025, Seattle, WA 98109, USA
Structure 19:7-15. 2011..Engineered homing endonucleases proteins are now being used to generate targeted genomic modifications for a variety of biotech and medical applications...
- Two-step red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coliB Karsten Tischer
Cornell University, Ithaca, NY, USA
Biotechniques 40:191-7. 2006....
- A synchronized quorum of genetic clocksTal Danino
Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, USA
Nature 463:326-30. 2010..Furthermore, it provides a specific model system for the generation of a mechanistic description of emergent coordinated behaviour at the colony level...
- Serine recombinases as tools for genome engineeringWilliam R A Brown
School of Biology, Queens Medical Centre, Nottingham NG7 2UH, UK
Methods 53:372-9. 2011....
- Tuning genetic control through promoter engineeringHal Alper
Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56 469, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 102:12678-83. 2005....
- Versatile RNA-sensing transcriptional regulators for engineering genetic networksJulius B Lucks
Department of Bioengineering, University of California, Berkeley, CA 94720, USA
Proc Natl Acad Sci U S A 108:8617-22. 2011..The combination of these three features within a single RNA-based regulatory mechanism has the potential to simplify the design and construction of genetic networks by directly propagating signals as RNA molecules...
- BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammalsIna Poser
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D 01307 Dresden, Germany
Nat Methods 5:409-15. 2008..The same high-throughput approach will be generally applicable to other model systems...
- Progress in metabolic engineering of Saccharomyces cerevisiaeElke Nevoigt
Department of Microbiology and Genetics, Berlin University of Technology, Seestr 13, 13353 Berlin, Germany
Microbiol Mol Biol Rev 72:379-412. 2008..resulted in substantial accumulated knowledge concerning genetics, physiology, and biochemistry as well as genetic engineering and fermentation technologies. S...
- Cancer regression in patients after transfer of genetically engineered lymphocytesRichard A Morgan
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Science 314:126-9. 2006..This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer...
- Engineering stability in gene networks by autoregulationA Becskei
EMBL, Structures and Biocomputing, Heidelberg, Germany
Nature 405:590-3. 2000..Here we have designed and constructed simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli and we show the gain of stability produced by negative feedback...
- Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesisD M McCarty
UNC Gene Therapy Center, University of North Carolina at Chapel Hill, NC, USA
Gene Ther 8:1248-54. 2001..These novel scAAV vectors represent a biochemical intermediate in rAAV transduction and should provide new insights into the biology of vector transduction...
- Microbial cellulose utilization: fundamentals and biotechnologyLee R Lynd
Chemical and Biochemical Engineering, Thayer School of Engineering and Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA
Microbiol Mol Biol Rev 66:506-77, table of contents. 2002....
- Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19James N Kochenderfer
Surgery Branch, National Cancer Institute, Bethesda, MD 20892, USA
Blood 116:4099-102. 2010..Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326...
- Genome-scale promoter engineering by coselection MAGEHarris H Wang
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA
Nat Methods 9:591-3. 2012..Promoter libraries can be quickly generated to study gain-of-function epistatic interactions in gene networks...
- Next-generation synthetic gene networksTimothy K Lu
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Nat Biotechnol 27:1139-50. 2009..As these challenges are addressed, synthetic biologists will be able to construct useful next-generation synthetic gene networks with real-world applications in medicine, biotechnology, bioremediation and bioenergy...
- Engineering a mevalonate pathway in Escherichia coli for production of terpenoidsVincent J J Martin
Department of Chemical Engineering, 201 Gilman Hall, University of California, Berkeley, California 94720 1462, USA
Nat Biotechnol 21:796-802. 2003....
- Genome engineeringPeter A Carr
Massachusetts Institute of Technology, Media Lab, Center for Bits and Atoms, Massachusetts, Cambridge, USA
Nat Biotechnol 27:1151-62. 2009..These developments promise genetic engineering with unprecedented levels of design originality and offer new avenues to expand both our understanding of ..
- Bioconversion of lignocellulosic biomass: biochemical and molecular perspectivesRaj Kumar
Radiation Biotechnology Unit, Division of Radiation Biology and Radiation Protection, Institute of Nuclear Medicine and Allied Sciences, New Delhi, 110054 India
J Ind Microbiol Biotechnol 35:377-91. 2008....
- Reprogramming cellular behavior with RNA controllers responsive to endogenous proteinsStephanie J Culler
Division of Chemistry and Chemical Engineering, 1200 East California Boulevard, MC 210 41, California Institute of Technology, Pasadena, CA 91125, USA
Science 330:1251-5. 2010..Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior...
- Ethanol production from xylose in engineered Saccharomyces cerevisiae strains: current state and perspectivesAkinori Matsushika
Biomass Technology Research Center, National Institute of Advanced Industrial Science and Technology, Kure, Hiroshima 737 0197, Japan
Appl Microbiol Biotechnol 84:37-53. 2009..cerevisiae. Recent studies using several promising approaches such as host strain selection and adaptation to obtain further improved xylose-utilizing S. cerevisiae are also addressed...
- Genetic engineering of algae for enhanced biofuel productionRandor Radakovits
Department of Chemistry and Geochemistry, Colorado School of Mines, Golden, CO 80401, USA
Eukaryot Cell 9:486-501. 2010..and other energy storage compounds in photosynthetic organisms, yeast, and bacteria through genetic engineering. Many improvements have been realized, including increased lipid and carbohydrate production, improved H(2) ..
- A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screenJason Moffat
Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA
Cell 124:1283-98. 2006..This work provides a widely applicable resource for loss-of-function screens, as well as a roadmap for its application to biological discovery...
- Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structureRichard Strasser
Institute of Applied Genetics and Cell Biology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
Plant Biotechnol J 6:392-402. 2008..The generated RNAi lines were stable, viable and did not show any obvious phenotype, thus providing a robust tool for the production of therapeutically relevant glycoproteins in plants with a humanized N-glycan structure...
- High-efficiency FLP and PhiC31 site-specific recombination in mammalian cellsChristopher S Raymond
Program in Developmental Biology, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
PLoS ONE 2:e162. 2007..Here we report the de novo synthesis of mouse codon-optimized FLP (FLPo) and PhiC31 (PhiC31o) SSRs, which result in recombination efficiencies similar to Cre...
- Manufacturing molecules through metabolic engineeringJay D Keasling
Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA
Science 330:1355-8. 2010..In any future, metabolic engineering will soon rival and potentially eclipse synthetic organic chemistry...
- From the Cover: Directed, efficient, and versatile modifications of the Drosophila genome by genomic engineeringJuan Huang
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
Proc Natl Acad Sci U S A 106:8284-9. 2009..We have successfully applied the genomic engineering scheme on 6 different genes and have generated at their loci more than 70 unique alleles...
- Encoding multiple unnatural amino acids via evolution of a quadruplet-decoding ribosomeHeinz Neumann
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
Nature 464:441-4. 2010..As ribo-Q1 independently decodes a series of quadruplet codons, this work provides foundational technologies for the encoded synthesis and synthetic evolution of unnatural polymers in cells...
- An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technologyAlexander M Aravanis
Department of Bioengineering, Stanford University Medical Center, Stanford, CA 94305, USA
J Neural Eng 4:S143-56. 2007....
- Modular control of multiple pathways using engineered orthogonal T7 polymerasesKarsten Temme
UCB UCSF Joint Graduate Group in Bioengineering, MC2540, Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94158, USA
Nucleic Acids Res 40:8773-81. 2012....
- An efficient xylose-fermenting recombinant Saccharomyces cerevisiae strain obtained through adaptive evolution and its global transcription profileYu Shen
The State Key Laboratory of Microbial Technology, Shandong University, Shan Da Nan Road 27, Jinan 250100, China
Appl Microbiol Biotechnol 96:1079-91. 2012..Furthermore, the deletion of PHO13 decreased the xylose growth in the respiration deficiency strain although deleting PHO13 can improve the xylose metabolism in other strains...
- Synthetic chromosome arms function in yeast and generate phenotypic diversity by designJessica S Dymond
High Throughput Biology Center, Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, Maryland 21205, USA
Nature 477:471-6. 2011..When complete, the fully synthetic genome will allow massive restructuring of the yeast genome, and may open the door to a new type of combinatorial genetics based entirely on variations in gene content and copy number...
- Synthetic gene networks that countAri E Friedland
Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for BioDynamics and Center for Advanced Biotechnology, Boston University, Boston, MA 02215, USA
Science 324:1199-202. 2009..These modular devices permit counting of varied user-defined inputs over a range of frequencies and can be expanded to count higher numbers...
- Customizing cell signaling using engineered genetic logic circuitsBaojun Wang
Department of Mathematics, Imperial College London, London, UK
Trends Microbiol 20:376-84. 2012....
- Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapyTimothy K Lu
Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 106:4629-34. 2009..This work establishes a synthetic biology platform for the rapid translation and integration of identified targets into effective antibiotic adjuvants...
- Late-acting dominant lethal genetic systems and mosquito controlHoang Kim Phuc
Department of Zoology, University of Oxford, South Parks Road, Oxford, UK
BMC Biol 5:11. 2007..Additionally, vector populations with strong density-dependent effects will tend to be resistant to SIT-based control as the population-reducing effect of induced sterility will tend to be offset by reduced density-dependent mortality...
- A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCRHiroki Torikai
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Blood 119:5697-705. 2012..CAR(+)TCR(neg) T cells of this type may potentially have efficacy as an off-the-shelf therapy for investigational treatment of B-lineage malignancies...
- From zero to hero--design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine productionJudith Becker
Institute of Biochemical Engineering, Technische Universitat Braunschweig, Braunschweig, Germany
Metab Eng 13:159-68. 2011..The design-based strategy for metabolic engineering reported here could serve as general concept for the rational development of microorganisms as efficient cellular factories for bio-production...
- A highly active synthetic mammalian retrotransposonJeffrey S Han
Department of Molecular Biology and Genetics and High Throughput Biology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nature 429:314-8. 2004..These synthetic retrotransposons are also the most highly active L1 elements known so far and have potential as practical tools for manipulating mammalian genomes...
- Engineering microbial consortia: a new frontier in synthetic biologyKatie Brenner
Division of Chemistry and Chemical Engineering, California Institute of Technology 210 41, Pasadena, CA 91125, USA
Trends Biotechnol 26:483-9. 2008..Here, we review recent efforts to engineer synthetic microbial consortia, and we suggest future applications...
- High efficiency recombineering in lactic acid bacteriaJan Peter van Pijkeren
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA
Nucleic Acids Res 40:e76. 2012..We expect that this work will serve as a blueprint for the adaptation of ssDNA recombineering to other gram-positive bacteria...
- Narrowing down the targets: towards successful genetic engineering of drought-tolerant cropsShujun Yang
Performance Plants Inc, 700 Gardiners Road, Kingston, Ontario, K7M 3X9, Canada
Mol Plant 3:469-90. 2010..The knowledge acquired will facilitate the genetic engineering of single or multiple targets and quantitative trait loci in key crops to create commercial-grade cultivars ..
- Tracking genome engineering outcome at individual DNA breakpointsMichael T Certo
Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington, USA
Nat Methods 8:671-6. 2011....
- Model-driven engineering of RNA devices to quantitatively program gene expressionJames M Carothers
California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley CA 94720, USA
Science 334:1716-9. 2011..More broadly, we provide a framework for studying RNA functions and illustrate the potential for the use of biochemical and biophysical modeling to develop biological design methods...
- Modified bases enable high-efficiency oligonucleotide-mediated allelic replacement via mismatch repair evasionHarris H Wang
Wyss Institute for Biologically Inspired Engineering, Harvard University, Department of Genetics, Harvard Medical School, Harvard University, Boston, MA 02115, USA
Nucleic Acids Res 39:7336-47. 2011..These results further elucidate the mechanism of oligo-mediated allelic replacement (OMAR) and enable improved methodologies for efficient, large-scale engineering of genomes...
- Recombinase-mediated cassette exchange (RMCE): traditional concepts and current challengesSoeren Turan
Hannover Medical School MHH, Experimental Hematology, Hannover, Germany
J Mol Biol 407:193-221. 2011..Remarkable efforts are noted in the framework of various mouse mutagenesis programs, which, in their first phase, have targeted virtually all genes and now start to shift their emphasis from gene trapping to gene modification...
- Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuelsSung Kuk Lee
Joint BioEnergy Institute, Emeryville, CA 95608, USA
Curr Opin Biotechnol 19:556-63. 2008....
- Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: application to open reading frame characterizationA J Link
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
J Bacteriol 179:6228-37. 1997..coli. Because these strains are isogenic with the exception of their deleted ORFs, they may be used in competition with one another to reveal phenotypes not apparent when cultured singly...
- Targeted gene addition into a specified location in the human genome using designed zinc finger nucleasesErica A Moehle
Sangamo BioSciences, Inc, Point Richmond Technology Center, 501 Canal Boulevard, Suite A100, Richmond, CA 94804, USA
Proc Natl Acad Sci U S A 104:3055-60. 2007....
- Protein sequestration generates a flexible ultrasensitive response in a genetic networkNicolas E Buchler
The Rockefeller University, New York, NY 10065, USA
Mol Syst Biol 5:272. 2009..The generation of flexible ultrasensitive responses is an unappreciated adaptive advantage that could explain the frequent evolutionary emergence of dominant negatives...
- Engineering biological systems with synthetic RNA moleculesJoe C Liang
Division of Chemistry and Chemical Engineering, 1200 E California Boulevard, MC 210 41, California Institute of Technology, Pasadena, CA 91125, USA
Mol Cell 43:915-26. 2011..Recent advances in implementing these engineered RNA molecules as key control elements in synthetic genetic networks are highlighting the functional relevance of this class of synthetic elements in programming cellular behaviors...
- Engineering yeasts for xylose metabolismThomas W Jeffries
USDA, Forest Service and University of Wisconsin Madison, Forest Products Laboratory, 53726, USA
Curr Opin Biotechnol 17:320-6. 2006..Lastly, strain selection through mutagenesis, adaptive evolution or from nature can also be employed to further improve activity...
- Engineered bidirectional communication mediates a consensus in a microbial biofilm consortiumKatie Brenner
Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210 41, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 104:17300-4. 2007..The microbial consensus consortium operates in diverse growth modes, including in a biofilm, where it sustains its response for several days...
- A reliable lacZ expression reporter cassette for multipurpose, knockout-first allelesGiuseppe Testa
BIOTEC, Technische Universitat Dresden, c o Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Genesis 38:151-8. 2004..Incorporation of site-specific recombination target sites creates a multipurpose allele for both knockout and conditional applications...
- Rapid profiling of a microbial genome using mixtures of barcoded oligonucleotidesJoseph R Warner
Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA
Nat Biotechnol 28:856-62. 2010..This approach can be applied to a broad range of traits to identify targets for future genome-engineering endeavors...
- Engineering Corynebacterium glutamicum for isobutanol productionKevin Michael Smith
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 5531 Boelter Hall, 420 Westwood Plaza, Los Angeles, CA 90095, USA
Appl Microbiol Biotechnol 87:1045-55. 2010..9 g/L isobutanol in a pycldh background. These results show promise in engineering C. glutamicum for higher chain alcohol production using the 2-keto acid pathways...
- Chloroplast-derived vaccines against human diseases: achievements, challenges and scopesAndreas G Lössl
Department of Applied Plant Sciences and Plant Biotechnology DAPP, University of Natural Resources and Applied Life Sciences BOKU, Vienna, Austria
Plant Biotechnol J 9:527-39. 2011..Particularly, plastid genetic engineering can be potentially used as a tool for cost-effective vaccine production...
- Metabolic engineering of a thermophilic bacterium to produce ethanol at high yieldA Joe Shaw
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA
Proc Natl Acad Sci U S A 105:13769-74. 2008....
- Engineering of a plasmid-free Escherichia coli strain for improved in vivo biosynthesis of astaxanthinKarin Lemuth
Institute of Microbiology, Universitat Stuttgart, Stuttgart, Germany
Microb Cell Fact 10:29. 2011..For the heterologous biosynthesis of astaxanthin in E. coli, however, the conversion of β-carotene to astaxanthin is obviously the most critical step towards an efficient biosynthesis of astaxanthin...
- Overproduction of free fatty acids in E. coli: implications for biodiesel productionXuefeng Lu
Department of Chemistry, Stanford University, Stanford CA 94305, USA
Metab Eng 10:333-9. 2008..coli strain, with a specific productivity of 0.024 g/h/g dry cell mass and a peak conversion efficiency of 4.8% of the carbon source into fatty acid products. At least 50% of the fatty acids produced were present in the free acid form...
- Lambda red recombineering in Escherichia coli occurs through a fully single-stranded intermediateJ A Mosberg
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Genetics 186:791-9. 2010..The mechanistic insights revealed by this work may facilitate further improvements to the versatility of lambda Red recombination...
- Terpenoids: opportunities for biosynthesis of natural product drugs using engineered microorganismsParayil Kumaran Ajikumar
Department of Chemical Engineering, Room 56 469, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Mol Pharm 5:167-90. 2008..This review focuses on the biodiversity of terpenoids, the biosynthetic pathways involved, and engineering efforts to maximize the production through these pathways...
- Genomic deletions created upon LINE-1 retrotranspositionNicolas Gilbert
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Cell 110:315-25. 2002..Thus, our data demonstrate multiple pathways for L1 integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence...
- Production of therapeutic proteins in algae, analysis of expression of seven human proteins in the chloroplast of Chlamydomonas reinhardtiiBeth A Rasala
Department of Cell Biology and the Skaggs Institute for Chemical Biology, La Jolla, CA, USA
Plant Biotechnol J 8:719-33. 2010..Thus, the success rate, expression levels, and bioactivity achieved demonstrate the utility of Chlamydomonas reinhardtii as a robust platform for human therapeutic protein production...
- Combinatorial engineering of microbes for optimizing cellular phenotypeChristine Nicole S Santos
Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56 469, Cambridge, MA 02139, United States
Curr Opin Chem Biol 12:168-76. 2008....
- Meganucleases and DNA double-strand break-induced recombination: perspectives for gene therapyFrédéric Pâques
Cellectis SA, 102, route de Noisy, 93 340 Romainville Cedex France
Curr Gene Ther 7:49-66. 2007..Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient...
- History of oncolytic viruses: genesis to genetic engineeringElizabeth Kelly
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
Mol Ther 15:651-9. 2007..Here, examination of early oncolytic virotherapy before genetic engineering serves to highlight tremendous advances, yet also hints at ways to penetrate host immune defenses, a ..
- Antioxidants in photosynthesis and human nutritionBarbara Demmig-Adams
Department of Environmental, Population, and Organismic Biology, University of Colorado, Boulder, CO 80309 0334, USA
Science 298:2149-53. 2002..The pathways that synthesize these compounds are becoming amenable to genetic manipulation, which may yield benefits as widespread as improved plant stress tolerance and improved human physical and mental health...
- Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleasesPilar Redondo
Macromolecular Crystallography Group, Spanish National Cancer Research Centre CNIO, c Melchor Fdez Almagro 3, 28029 Madrid, Spain
Nature 456:107-11. 2008....
- Fermentative butanol production by ClostridiaSang Yup Lee
Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering BK21 Program, Korea Advanced Institute of Science and Technology, Yuseong Gu, Daejeon 305 701, Republic of Korea
Biotechnol Bioeng 101:209-28. 2008..The strategies for strain improvement by metabolic engineering and further requirements to make fermentative butanol production a successful industrial process are also discussed...
- Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systemsYvonne Y Chen
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Proc Natl Acad Sci U S A 107:8531-6. 2010..By providing tight gene-expression control with customizable ligand inputs, RNA-based regulatory systems can greatly improve cellular therapies and advance broad applications in health and medicine...
- Synthetic viruses: a new opportunity to understand and prevent viral diseaseEckard Wimmer
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA
Nat Biotechnol 27:1163-72. 2009..Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair-deoptimized polioviruses...
- Engineering of promoter replacement cassettes for fine-tuning of gene expression in Saccharomyces cerevisiaeElke Nevoigt
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Appl Environ Microbiol 72:5266-73. 2006..cerevisiae was replaced by five TEF1 promoter mutants of different strengths, which allowed analysis of the impact of glycerol 3-phosphate dehydrogenase activity on the glycerol yield...
- Role of CD44 in experimental Multiple SclerosisMitzi Nagarkatti; Fiscal Year: 2013..abstract_text> ..
- O-GlcNAc Modification in Metabolic HomeostasisXiaoyong Yang; Fiscal Year: 2013..Pharmacological intervention to reset O-GlcNAc levels may represent an innovative strategy for preventing and treating metabolic syndrome. ..
- Genetics and Molecular Biology of Striated Muscle MyosinSanford I Bernstein; Fiscal Year: 2013..Overall our project will take advantage of an innovative experimental system to test significant questions regarding basic myosin function and disease. ..
- Oxidative Stress and Vascular HO in DiabetesNader G Abraham; Fiscal Year: 2010..It will allow for the first time, an in-depth analysis of the function of HO-1 in vascular protection and for the development of innovative gene-targeting therapies for the treatment of type I diabetes. ..
- Molecular Imaging of Protease Activation in AneurysmMehran M Sadeghi; Fiscal Year: 2013..Furthermore, this approach may be applied to risk assessment and management of other vascular diseases, which together with aneurysm,are leading causes of mortality amongst veterans. ..
- Somatic cell gene transfer/neurological &clinical applicationsEn Ju Lin; Fiscal Year: 2013..We will genetically modify these cells to see if we can reduce seizures in an animal model of epilepsy with a second part of the project developing a safer way to control our genetic intervention. ..
- Identification of Transcriptional Biomarkers of Calorie Restriction in Adipose TiJAMIE LOUIS BARGER; Fiscal Year: 2010....
- BEHAVIORAL CORELennart Mucke; Fiscal Year: 2013..abstract_text> ..
- THE PATHOBIOLOGY OF INHERITED RETINAL DEGENERATIONDean Bok; Fiscal Year: 2006..abstract_text> ..
- NORMAL/PATHOLOGIC GENE EXPRESSION IN HEMATOPOIETIC CELLSGORDON GINDER; Fiscal Year: 1993..The long term goal of this proposed Center of Excellence is to elucidate basic molecular mechanisms of disabling hematological diseases and apply this knowledge to innovative somatic genetic therapy approaches to treat these diseases...
- Hyperglycemia, Aldose Reducatse & Murine AtherosclerosisIra Goldberg; Fiscal Year: 2005..This is significant because it will provide for a model to study this complication and suggest a therapeutic target for prevention of diabetic macrovascular disease. ..
- Blocking of HIV Chemokine Receptors By IntrabodiesBruce Torbett; Fiscal Year: 2004..Lastly, our proposed studies will contribute basic and pre-clinical insights into the feasibility of using HIV vectors to deliver and maintain ectopic gene expression in hematopoietic cells. ..
- Shifting Conceptions of Human IdentityMICHAEL BESS; Fiscal Year: 2005..abstract_text> ..
- NEURAL BASIS OF INTERNAL REPRESENTATION OF PLACEBruce McNaughton; Fiscal Year: 2009..A well characterized and well understood rodent model of hippocampal function will also provide a platform for drug discovery and the development of genetic intervention for treatment of human memory disorder. ..
- Non-invasive cardio-pulmonary monitor for miceMartin Baruch; Fiscal Year: 2007..is growing along with an increasing population of mice strains that are being used to test drug responses, genetic engineering attempts, and other factors that can affect these biological rhythms...
- Generation of kinase-resistant NMDA receptors by gene-targeting in the mouseJohn Leonard; Fiscal Year: 2009..These mice will be made available as a research tool for neuroscientists worldwide. ..
- STRUCTURE OF RIBONUCLEIC ACIDSStephen Harvey; Fiscal Year: 2005..This research will include development of a library of RNA structural motifs derived from the Nucleic Acid Database, along with tools for incorporating these motifs into structural models. ..
- New Genetic Intervention for Healthy AgingJames Nelson; Fiscal Year: 2005..A PTP-1B-/- longevity mutant would also provide a new target for pharmacologic interventions to retard aging. ..
- GENE THERAPY FOR OVARIAN CANCERDavid Curiel; Fiscal Year: 1999..Finally, in vivo studies will be carried out to develop the methods for translation of these strategies into a gene therapy approach for ovarian carcinoma. ..
- Limbic Dopaminergic System in Major DepressionGregory Ordway; Fiscal Year: 2005..Uncovering the potential role of DA in the pathobiology of depression may lead to advancements in the pharmacological, and possibly genetic, intervention of major depression. ..
- EVALUATING USE OF GENETIC INFORMATION: A MODEL PROCESSWylie Burke; Fiscal Year: 2003..5. To conduct an evaluation of the model process within a large health care system. ..
- MUCOSAL GENE TRANSFER USING DENDRIMER POLYMERSJames Baker; Fiscal Year: 1999..The results of these studies will provide basic information about gene delivery that should allow further refinements in protocols and agents for endobronchial gene transfer. ..
- SUBSTRATE METABOLISM IN ISOLATED MYOCYTES IN SHOCKMaw Shung Liu; Fiscal Year: 2002..The results obtained will lay the groundwork for future therapy by drugs or genetic intervention to preserve cardiac function during sepsis. ..
- Genetic Determination of Host Processes for HIV-1Shigemi Kinoshita; Fiscal Year: 2004..Findings from this project will allow us to characterize the biology of HIV-1 in human cells in greater detail and will provide new approaches to exploit molecular genetic intervention to understand and treat AIDS. ..
- Tolerance to Carbohydrate Antigens in TransplantationDavid Cooper; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Biosensors for metabolic engineeringJay Keasling; Fiscal Year: 2006..abstract_text> ..
- Chimeric Nucleases for Gene Targeting in DrosophilaDana Carroll; Fiscal Year: 2003..To test the generality of the method, it will be applied to a second Drosophila locus, the rosy (ry) gene. ..
- Thromboregulation to Prevent Thrombotic MicroangiopathyDavid Cooper; Fiscal Year: 2008..It is anticipated that these approaches will abrogate the development of TM and allow long-term survival of pig organs in baboons. ..
- Stimulating Gene Targeting with Zinc Finger NucleasesDana Carroll; Fiscal Year: 2004..To demonstrate the generality of this approach to gene targeting, it will be applied to another mouse locus, the Rpo2-1 gene. ..
- GENETIC AND BIOCHEMICAL STUDIES OF PHOB ACTIVATIONWILLIAM MCCLEARY; Fiscal Year: 2003..An increased understanding of these signal transduction proteins will assist in the rational design of drugs to combat pathogens. ..
- SALIVARY PROTEINS IN DENTAL INTEGUMENTSFRANK OPPENHEIM; Fiscal Year: 2009..abstract_text> ..
- Studies of naturally occurring structurally modified carbohydratesXi Chen; Fiscal Year: 2010..abstract_text> ..
- A POLYMERIC DRUG DELIVERY SYSTEM FOR CANCER THERAPYJINDRICH H KOPECEK; Fiscal Year: 2010..The concept of double-targeted macromolecular therapeutics provides a new paradigm for the design of efficient anticancer drugs for the treatment of ovarian cancer. ..
- Engineering AAV Vectors to Evade Antibody NeutralizationDavid V Schaffer; Fiscal Year: 2010..Furthermore, it will yield insights into the responses of other immune system components to AAV. ..
- Neural Progenitor Cells as Cancer Therapy VectorsKaren Aboody; Fiscal Year: 2009..The described approach might then be adapted to the treatment of other solid tumors by careful choice of appropriate therapeutic transgenes. ..
- DNA Patent Policies at Academic InstitutionsLeRoy Walters; Fiscal Year: 2003..S. and Canadian academic institutions. ..
- Mucosal Immunization with a Vaccinia Virus-Based VectorBertram Jacobs; Fiscal Year: 2003..Animals will be immunized intra-nasally either with virus alone or as part of a prime-boost regime. Systemic, nasal and vaginal immune responses to the HIV multi-epitope polypeptide will be analyzed. ..
- BD Biosciences FACS Canto Flow CytometerLAWRENCE LAMB; Fiscal Year: 2006..The laboratory will require an instrument that will serve the laboratory in the development and execution of advanced cell therapy trials. [unreadable] [unreadable]..
- The Role of Metabolic Signaling in Longevity RegulationSu Ju Lin; Fiscal Year: 2010..Many cellular pathways are conserved in yeast and mammals. Therefore, insight into these molecular processes in yeast will also provide clues to the molecular basis of human aging and age-associated diseases. ..
- EUROPIC america 2002: a conference for picornavirusesEckard Wimmer; Fiscal Year: 2002..The over will discuss the difficulties (circulation of vaccine strains, recent outbreak of poliomyelitis in the Western Hemisphere) that have emerged during the current, historic effect to globally eradicate poliovirus. ..
- REGULATION OF B LYMPHOMA GROWTH AND APOPTOSISDavid Scott; Fiscal Year: 2001..The results of these studies will provide information on regulation of neoplastic growth as well as mechanism for inducing apoptosis in a model for deletional tolerance. ..
- TOOLS FOR PUBLIC CONVERSATION ABOUT BEHAVIORAL GENETICSErik Parens; Fiscal Year: 2001....
- SHIGA LIKE TOXIN AND RENAL CELL DYSFUNCTIONDonald Kohan; Fiscal Year: 2001..These studies provide essential information on how and why HGEN are damaged in HUS. ..
- Structure/function analysis of the E. coli NIR/NRII signal transduction systemAlexander Ninfa; Fiscal Year: 2009..Our studies with a model system should allow rapid progress. ..
- Cellular Injury and AdaptationJ Cobb; Fiscal Year: 2008..A well-characterized therapy that improves Th1 responsiveness and survival after CLP, systemic IL-12, will be used to perturb the system, testing the robustness of the models. ..
- XENOBIOTICS AND ALLERGIC INFLAMMATIONAndrew Saxon; Fiscal Year: 2005..The projects are supported by a DEP collection and fractionation core, a mouse core, and a administrative, patient and sample coordination core. ..
- Approach for amplification of molecular signalsALEXEY ZDANOVSKY; Fiscal Year: 2005..Bacterial luciferase will be incorporated in the naturally existing cascades of enzymatic reactions to produce an inexpensive and simple assay for the detection of antigens of interest including those of biowarfare agents. ..
- BLUETONGUE VIRUS MORPHOGENESISPolly Roy; Fiscal Year: 2005..Together with the proposed experimental programme, our reagent and knowledge base will allow us to complete the tasks we have specified to offer new insights into virus replication and new suggestions for effective control. ..
- Suspension arrays detection/quantification of antibodiesALEXEY ZDANOVSKY; Fiscal Year: 2005....
- Structure and Function of IRES ElementsEckard Wimmer; Fiscal Year: 2006..We will investigate the molecular reason for this attenuation. Finally, we will determine whether we can exchange viral IRESs also IRESs of cellular mRNA. ..
- MICROBIAL DEGRADATION OF AGENT ORANGEAnanda Chakrabarty; Fiscal Year: 2004..The progress achieved and the ways we intend to meet our goals are detailed in this proposal ..
- Role of the E3L gene in poxvirus pathogenesisBertram Jacobs; Fiscal Year: 2007..Thus, this work will lead to translation of basic molecular knowledge of E3L function into clinically relevant applications. ..
- Characterization of microRNA cell death regulatorsBruce Hay; Fiscal Year: 2007..Therefore, it is likely that successful completion of the proposed experiments will increase our understanding of how cell death is regulated in human health and disease. [unreadable] [unreadable] [unreadable]..
- APP-BP1, The Cell Cycle, and Alzheimer DiseaseRachael Neve; Fiscal Year: 2007..We will test whether these predictions are correct. [unreadable] [unreadable]..
- Novel Strategy for Animal Model Testing of HCMV VaccinesMark Schleiss; Fiscal Year: 2007..These studies will represent the first efficacy test of a human CMV subunit vaccine in a small animal model of congenital CMV infection. [unreadable] [unreadable]..
- Engineering Novel AAV Vectors for Retinal Gene TherapyDavid Schaffer; Fiscal Year: 2007..The novel approaches developed in this work will have general impact for the molecular engineering of enhanced viral gene delivery vehicles for a number of retinal diseases. [unreadable] [unreadable] [unreadable]..
- Nonapoptotic roles for proteases in spermatogenesisBruce Hay; Fiscal Year: 2008..In addition this work is likely to provide insight into the mechanisms by which caspase activity, and the consequences of caspase activation, are regulated. ..
- Pathogenesis of EAST1 toxin in ETEC associated diarrhea diseaseWeiping Zhang; Fiscal Year: 2008..The determination of virulence significance of EAST1 toxin in diarrheal disease will provide essential information to prevent or control this disease. [unreadable] [unreadable] [unreadable] [unreadable]..
- Blood Systems BiologyDaniel Hammer; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Target Specificity of the Yeast Retrotransposon Ty5Daniel Voytas; Fiscal Year: 2005....
- GENETIC AND CHEMICAL APPROACHES TO NOVEL LIPID II BINDING PEPTIDE ANTIBIOTICSXihou Yin; Fiscal Year: 2010..Understanding the molecular basis of enduracidin resistance in the producing organism will help predict how new antibiotics may be affected by existing resistance mechanisms and provide insight into ways that resistance may emerge. ..