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1.
Annu Rev Immunol ; 38: 705-725, 2020 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-32340571

RESUMO

The discovery of CD4+ T cell subset-defining master transcription factors and framing of the Th1/Th2 paradigm ignited the CD4+ T cell field. Advances in in vivo experimental systems, however, have revealed that more complex lineage-defining transcriptional networks direct CD4+ T cell differentiation in the lymphoid organs and tissues. This review focuses on the layers of fate decisions that inform CD4+ T cell differentiation in vivo. Cytokine production by antigen-presenting cells and other innate cells influences the CD4+ T cell effector program [e.g., T helper type 1 (Th1), Th2, Th17]. Signals downstream of the T cell receptor influence whether individual clones bearing hallmarks of this effector program become T follicular helper cells, supporting development of B cells expressing specific antibody isotypes, or T effector cells, which activate microbicidal innate cells in tissues. These bifurcated, parallel axes allow CD4+ T cells to augment their particular effector program and prevent disease.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/citologia , Diferenciação Celular/genética , Citocinas/metabolismo , Humanos , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
2.
Cell ; 184(1): 169-183.e17, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33296701

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is causing a global pandemic, and cases continue to rise. Most infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that could contribute to immunity. We performed a longitudinal assessment of individuals recovered from mild COVID-19 to determine whether they develop and sustain multifaceted SARS-CoV-2-specific immunological memory. Recovered individuals developed SARS-CoV-2-specific immunoglobulin (IgG) antibodies, neutralizing plasma, and memory B and memory T cells that persisted for at least 3 months. Our data further reveal that SARS-CoV-2-specific IgG memory B cells increased over time. Additionally, SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral function: memory T cells secreted cytokines and expanded upon antigen re-encounter, whereas memory B cells expressed receptors capable of neutralizing virus when expressed as monoclonal antibodies. Therefore, mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks of antiviral immunity.


Assuntos
COVID-19/imunologia , COVID-19/fisiopatologia , Memória Imunológica , SARS-CoV-2/fisiologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Linfócitos B/imunologia , COVID-19/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/química , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/metabolismo , Linfócitos T/imunologia
3.
Cell ; 183(5): 1367-1382.e17, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33160446

RESUMO

A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Nanopartículas/química , Domínios Proteicos/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/química , Vacinação , Adolescente , Adulto , Idoso , Animais , COVID-19/virologia , Chlorocebus aethiops , Estudos de Coortes , Epitopos/imunologia , Feminino , Células HEK293 , Humanos , Macaca nemestrina , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero , Adulto Jovem
4.
Immunity ; 57(4): 843-858.e5, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38513666

RESUMO

Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we showed that IL-4 cytokine signaling in GC B cells directly downregulated the transcription factor BCL6 via negative autoregulation to release cells from the GC program and to promote MBC formation. This selection event required additional survival cues and could therefore result in either GC exit or death. We demonstrate that both increasing IL-4 bioavailability or limiting IL-4 signaling disrupted MBC selection stringency. In this way, IL-4 control of BCL6 expression serves as a tunable switch within the GC to tightly regulate MBC selection and affinity maturation.


Assuntos
Interleucina-4 , Fatores de Transcrição , Linfócitos B , Centro Germinativo , Interleucina-4/metabolismo , Células B de Memória , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Fatores de Transcrição/metabolismo
5.
Proc Natl Acad Sci U S A ; 117(12): 6675-6685, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32152119

RESUMO

A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a high-throughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The early memory B cell (MBC) response was mediated by both classical immunoglobulin M (IgM) (IgM+CD27+) and switched immunoglobulin (swIg+) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg+ and atypical IgM+ and IgD+ MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.


Assuntos
Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Linfócitos B/imunologia , Memória Imunológica/imunologia , Vacina contra Febre Amarela/imunologia , Febre Amarela/prevenção & controle , Vírus da Febre Amarela/imunologia , Adulto , Humanos , Vacinação , Vacinas Atenuadas/imunologia , Proteínas do Envelope Viral/imunologia , Replicação Viral , Febre Amarela/imunologia , Febre Amarela/virologia , Vacina contra Febre Amarela/administração & dosagem
6.
Am J Med Genet A ; 164A(11): 2892-900, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25251875

RESUMO

Mutations in ERCC6 are associated with growth failure, intellectual disability, neurological dysfunction and deterioration, premature aging, and photosensitivity. We describe siblings with biallelic ERCC6 mutations (NM_000124.2:c. [543+4delA];[2008C>T]) and brain hypomyelination, microcephaly, cognitive decline, and skill regression but without photosensitivity or progeria. DNA repair assays on cultured skin fibroblasts confirmed a defect of transcription-coupled nucleotide excision repair and increased ultraviolet light sensitivity. This report expands the disease spectrum associated with ERCC6 mutations.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , DNA Helicases/genética , Enzimas Reparadoras do DNA/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso/genética , Processamento Alternativo , Biomarcadores/metabolismo , Criança , Pré-Escolar , DNA Helicases/metabolismo , Análise Mutacional de DNA , Enzimas Reparadoras do DNA/metabolismo , Fácies , Feminino , Expressão Gênica , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico , Humanos , Íntrons , Imageamento por Ressonância Magnética , Masculino , Mutação , Doenças do Sistema Nervoso/diagnóstico , Linhagem , Fenótipo , Proteínas de Ligação a Poli-ADP-Ribose , Irmãos
7.
bioRxiv ; 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36747852

RESUMO

Germinal center (GC)-derived memory B cells (MBCs) are critical for humoral immunity as they differentiate into protective antibody-secreting cells during re-infection. GC formation and cellular interactions within the GC have been studied in detail, yet the exact signals that allow for the selection and exit of MBCs are not understood. Here, we show that IL-4 signaling in GC B cells directly downregulates BCL6 via negative autoregulation to release cells from the GC program and promote MBC formation. This selection event requires additional survival cues and can therefore result in either GC exit or death. We demonstrate that both increasing IL-4 bioavailability or limiting IL-4 signaling disrupt MBC selection stringency. In this way, IL-4 control of BCL6 expression serves as a tunable switch within the GC to tightly regulate MBC selection and affinity maturation.

8.
Cell Rep Med ; 3(10): 100780, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36206752

RESUMO

Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.


Assuntos
HIV-1 , Nanopartículas , Vacinas , Anticorpos Anti-HIV , Formação de Anticorpos , Glicoproteínas
9.
Cell Host Microbe ; 29(4): 594-606.e6, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33711270

RESUMO

CD4 T cell effector function is required for optimal containment of Mycobacterium tuberculosis (Mtb) infection. IFNÉ£ produced by CD4 T cells is a key cytokine that contributes to protection. However, lung-infiltrating CD4 T cells have a limited ability to produce IFNÉ£, and IFNÉ£ plays a lesser protective role within the lung than at sites of Mtb dissemination. In a murine infection model, we observed that IFNÉ£ production by Mtb-specific CD4 T cells is rapidly extinguished within the granuloma but not within unaffected lung regions, suggesting localized immunosuppression. We identified a signature of TGFß signaling within granuloma-infiltrating T cells in both mice and rhesus macaques. Selective blockade of TGFß signaling in T cells resulted in an accumulation of terminally differentiated effector CD4 T cells, improved IFNÉ£ production within granulomas, and reduced bacterial burdens. These findings uncover a spatially localized immunosuppressive mechanism associated with Mtb infection and provide potential targets for host-directed therapy.


Assuntos
Granuloma/imunologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/metabolismo , Tuberculose/imunologia , Imunidade Adaptativa , Animais , Linfócitos T CD4-Positivos , Morte Celular , Citocinas , Modelos Animais de Doenças , Feminino , Granuloma/microbiologia , Inflamação , Interferon gama , Pulmão/microbiologia , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis , Células Th1
10.
Sci Adv ; 6(30): eaay2922, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32832653

RESUMO

Recombination systems are widely used as bioengineering tools, but their sites have to be highly similar to a consensus sequence or to each other. To develop a recombination system free of these constraints, we turned toward attC sites from the bacterial integron system: single-stranded DNA hairpins specifically recombined by the integrase. Here, we present an algorithm that generates synthetic attC sites with conserved structural features and minimal sequence-level constraints. We demonstrate that all generated sites are functional, their recombination efficiency can reach 60%, and they can be embedded into protein coding sequences. To improve recombination of less efficient sites, we applied large-scale mutagenesis and library enrichment coupled to next-generation sequencing and machine learning. Our results validated the efficiency of this approach and allowed us to refine synthetic attC design principles. They can be embedded into virtually any sequence and constitute a unique example of a structure-specific DNA recombination system.

11.
medRxiv ; 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32817957

RESUMO

The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. The majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that might contribute to herd immunity. Thus, we performed a longitudinal assessment of individuals recovered from mildly symptomatic COVID-19 to determine if they develop and sustain immunological memory against the virus. We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset. Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies. These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.

12.
Res Sq ; 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32818218

RESUMO

The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. The majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that might contribute to herd immunity. Thus, we performed a longitudinal assessment of individuals recovered from mildly symptomatic COVID-19 to determine if they develop and sustain immunological memory against the virus. We found that recovered individuals developed SARS-CoV-2-specific IgG antibody and neutralizing plasma, as well as virus-specific memory B and T cells that not only persisted, but in some cases increased numerically over three months following symptom onset. Furthermore, the SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral immunity: memory T cells secreted IFN-γ and expanded upon antigen re-encounter, while memory B cells expressed receptors capable of neutralizing virus when expressed as antibodies. These findings demonstrate that mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks associated with antiviral protective immunity.

13.
bioRxiv ; 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32817941

RESUMO

A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.

14.
Nat Commun ; 10(1): 1126, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30850611

RESUMO

Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants and young children. Although it is widely agreed that an RSV vaccine should induce both mucosal and systemic antibody responses, little is known about the B cell response to RSV in mucosa-associated lymphoid tissues. Here, we analyze this response by isolating 806 RSV F-specific antibodies from paired adenoid and peripheral blood samples from 4 young children. Overall, the adenoid-derived antibodies show higher binding affinities and neutralization potencies compared to antibodies isolated from peripheral blood. Approximately 25% of the neutralizing antibodies isolated from adenoids originate from a unique population of IgM+ and/or IgD+ memory B cells that contain a high load of somatic mutations but lack expression of classical memory B cell markers. Altogether, the results provide insight into the local B cell response to RSV and have implications for the development of vaccines that stimulate potent mucosal responses.


Assuntos
Tonsila Faríngea/imunologia , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Linfócitos B/imunologia , Imunidade nas Mucosas , Leucócitos Mononucleares/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Tonsila Faríngea/virologia , Afinidade de Anticorpos , Especificidade de Anticorpos , Linfócitos B/virologia , Biomarcadores/metabolismo , Pré-Escolar , Clonagem Molecular , Feminino , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Humanos , Imunoglobulina D/biossíntese , Imunoglobulina M/biossíntese , Leucócitos Mononucleares/virologia , Masculino , Mutação , Especificidade de Órgãos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
15.
Cell Rep ; 28(13): 3300-3308.e4, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31553901

RESUMO

Monoclonal antibodies (mAbs) have recently emerged as one of the most promising classes of biotherapeutics. A potential advantage of B cell-derived mAbs as therapeutic agents is that they have been subjected to natural filtering mechanisms, which may enrich for B cell receptors (BCRs) with favorable biophysical properties. Here, we evaluated 400 human mAbs for polyreactivity, hydrophobicity, and thermal stability using high-throughput screening assays. Overall, mAbs derived from memory B cells and long-lived plasma cells (LLPCs) display reduced levels of polyreactivity, hydrophobicity, and thermal stability compared with naive B cell-derived mAbs. Somatic hypermutation (SHM) is inversely associated with all three biophysical properties, as well as BCR expression levels. Finally, the developability profiles of the human B cell-derived mAbs are comparable with those observed for clinical mAbs, suggesting their high therapeutic potential. The results provide insight into the biophysical consequences of affinity maturation and have implications for therapeutic antibody engineering and development.


Assuntos
Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos/imunologia , Humanos , Conformação Molecular
16.
Sci Total Environ ; 634: 20-28, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29626767

RESUMO

Environmental chemicals, particularly organochlorinated contaminants (OCs), are associated with a ranged of adverse health effects, including impairment of the immune system and antiviral immunity. Influenza A virus (IAV) is an infectious disease of major global public health concern and exposure to OCs can increase the susceptibility, morbidity, and mortality to disease. It is however unclear how pollutants are interacting and affecting the outcome of viral infections at the cellular level. In this study, we investigated the effects of a mixture of environmentally relevant OCs on IAV infectivity upon in vitro exposure in Madin Darby Canine Kidney (MDCK) cells and human lung epithelial cells (A549). Exposure to OCs reduced IAV infectivity in MDCK and A549 cells during both short (18-24h) and long-term (72h) infections at 0.05 and 0.5ppm, and effects were more pronounced in cells co-treated with OCs and IAV than pre-treated with OCs prior to IAV (p<0.001). Pre-treatment of host cells with OCs did not affect IAV cell surface attachment or entry. Visualization of IAV by transmission electron microscopy revealed increased envelope deformations and fewer intact virions during OC exposure. Taken together, our results suggest that disruption of IAV infection upon in vitro exposure to OCs was not due to host-cell effects influencing viral attachment and entry, but perhaps mediated by direct effects on viral particles or cellular processes involved in host-virus interactions. In vitro infectivity studies such as ours can shed light on the complex processes underlying host-pathogen-pollutant interactions.


Assuntos
Poluentes Ambientais/toxicidade , Vírus da Influenza A/fisiologia , Animais , Cães , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana , Células Madin Darby de Rim Canino
17.
PLoS One ; 11(1): e0147494, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26799494

RESUMO

Two-component signaling (2CS) systems enable bacterial cells to respond to changes in their local environment, often using a membrane-bound sensor protein and a cytoplasmic responder protein to regulate gene expression. Previous work has shown that Escherichia coli's natural EnvZ/OmpR 2CS could be modified to construct a light-sensing bacterial photography system. The resulting bacterial photographs, or "coliroids," rely on a phosphotransfer reaction between Cph8, a synthetic version of EnvZ that senses red light, and OmpR. Gene expression changes can be visualized through upregulation of a LacZ reporter gene by phosphorylated OmpR. Unfortunately, basal LacZ expression leads to a detectable reporter signal even when cells are grown in the light, diminishing the contrast of the coliroids. We performed site-directed mutagenesis near the phosphotransfer site of Cph8 to isolate mutants with potentially improved image contrast. Five mutants were examined, but only one of the mutants, T541S, increased the ratio of dark/light gene expression, as measured by ß-galactosidase activity. The ratio changed from 2.57 fold in the starting strain to 5.59 in the T541S mutant. The ratio decreased in the four other mutant strains we examined. The phenotype observed in the T541S mutant strain may arise because the serine sidechain is chemically similar but physically smaller than the threonine sidechain. This may minimally change the protein's local structure, but may be less sterically constrained when compared to threonine, resulting in a higher probability of a phosphotransfer event. Our initial success pairing synthetic biology and site-directed mutagenesis to optimize the bacterial photography system's performance encourages us to imagine further improvements to the performance of this and other synthetic systems, especially those based on 2CS signaling.


Assuntos
Mutagênese Sítio-Dirigida/métodos , Transdução de Sinais/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/fisiologia , Escherichia coli/genética , Escherichia coli/fisiologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/fisiologia , Regulação Bacteriana da Expressão Gênica/genética , Óperon Lac/genética , Óperon Lac/fisiologia , Luz , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/fisiologia , Organismos Geneticamente Modificados/genética , Organismos Geneticamente Modificados/fisiologia , Fotografação , Transativadores/genética , Transativadores/fisiologia , beta-Galactosidase/metabolismo
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