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Her research focuses on the study of virology, specifically viral persistence and reservoirs, as well as viral drug resistance.

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The lab aims to: understand the mechanisms that allow HIV to persist during antiretroviral therapy; develop practical, affordable tests to detect drug-resistant HIV; make insights into reservoirs of drug-resistant HIV and illuminate the pathogenesis of HIV-related diseases. Research areas of focus include viral treatment, transmission and dissemination; viral persistence and reservoirs; and viral drug resistance.

In particular, we investigate the role of maternal microchimerism maternal cells acquired by the fetus in utero in fetal and infant immune development, early vaccine response and susceptibility to infection, including malaria and HIV.

Workshop | Center for Viral Systems Biology

Heather Jaspan's lab seeks to: identify correlates of HIV risk at mucosal surfaces, namely the infant gut and the adolescent genital tract; study the role of the commensal bacteria at these mucosal surfaces in modulating immunity; understand immunity of infants born to HIV-infected mothers, who are uninfected yet have high morbidity and mortality; identify vaccination strategies that reduce HIV infection; and improve infectious morbidities in these vulnerable HIV-exposed infants.

Research areas of focus include virology and bacteriology, specifically viral immunology, mucosal virome and mucosal microbiota. The Kappe Lab is focused on understanding the complex biology of the malaria parasite and the immune responses to infection, using this information to design transformational interventions that will help win the fight against malaria.

Research areas of focus include cell and molecular biology, biotechnology, genetic engineering, drug resistance, systems biology, global health, host-pathogen interaction, immunology, infectious disease, vaccine development and genetically attenuated parasite GAP strains for vaccination. The Kaushansky Lab works with the pathogens of infectious diseases like malaria that infect hundreds of millions of people every year. Research areas of focus include malaria host-parasite interaction; host-based drug discovery; cross-pathogen studies and co-infections; global health; immunology and infectious disease.

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  • The Myler Lab uses cutting-edge genomic, bioinformatic and molecular approaches to study gene function and protein structure in a variety of infectious disease organisms. The Parsons Lab works on two infectious diseases that are especially prevalent in low-income populations of the world: human African trypanosomiasis also known as African sleeping sickness and toxoplasmosis.

    The lab focuses on the human pathogens group B Streptococcus and Staphylococcus aureus. Research areas of focus include bacteriology, specifically bacterial pathogenesis, bacterial virulence and animal models of human disease. The Sather Lab studies the interactions between invading pathogens and the host immune system, with the goal of leveraging these discoveries toward the development of novel vaccines and vaccination regimens.

    Research areas of focus include systems biology, genetic engineering, global health, genetics, host-pathogen interaction, infectious disease and immunology. The Sherman Lab is focused on developing novel drugs, diagnostics and vaccines to combat tuberculosis. The Smith Lab studies the biology of the Plasmodium malaria parasite during the blood stage. This review focuses on a protein microarray approach for this purpose. The results of these studies lead to the identification of diagnostic markers and potential subunit vaccine candidates. These results from over 30 different organisms can also provide information about common trends in the humoral immune response.

    A systems biology approach to identify the antibody repertoire associated with infectious diseases challenge using protein microarray has become a powerful method in identifying diagnostic markers and potential subunit vaccine candidates, and moreover, in providing information on proteomic feature functional and physically properties of seroreactive and serodiagnostic antigens.

    Infectious Diseases - How do we control them?

    Combining the detection of the pathogen with a comprehensive assessment of the host immune response will provide a new understanding of the correlations between specific causative agents, the host response, and the clinical manifestations of the disease. Correspondence to Philip L.

    Download Systems Biological Approaches In Infectious Diseases Progress In Drug Research

    A major component of the adaptive immune response to infection is the generation of protective and long-lasting humoral immunity. Analyses of antibody responses against different infectious agents are critical for diagnosing infectious diseases, understanding pathogenic mechanisms, and the development and evaluation of vaccines. Protein microarrays are well suited to identify, quantify, and compare individual antigenic responses following exposure to infectious agents.

    It can now evaluate antibody responses to hundreds, or even thousands, of recombinant antigens at one time. These large-scale studies have uncovered new antigenic targets, provided new insights into vaccine research and yielded an overview of immunoreactivity against almost the entire proteome of certain pathogens.

    This technology can be applied to the development of improved serodiagnostic tests, discovery of subunit vaccine antigen candidates, epidemiologic research, and vaccine development, as well as providing novel insights into infectious disease and the immune system. In this review, we will discuss the use of protein microarrays as a powerful tool to define the humoral immune response to bacteria and viruses. Factors governing selection of the particular antigens recognized are unclear [1,2]. It is not uncommon for viruses encoding a small number of proteins to generate antibodies against each encoded protein.

    But for infectious agents containing hundreds or thousands of proteins only a subset of the proteome is recognized and little is known about the extent or the characteristics of this subset of antigens. Methods for making a complete empirical accounting of the immunoproteome have limitations, particularly when the genome of the organism is large.

    The Protein Microarray Laboratory at University of California Irvine has developed a highly efficient method to determine the humoral immune response to microbial antigens. After launching this project 10 years ago, we have made more than 40 plasmids, printed the encoded proteins on 25 microarrays and probed the arrays with 15 serum specimens in order to determine disease-associated antibody profiles in people infected with each agent.

    These chips can be probed with sera from infected patients to determine the immunodominant antigens for each agent and the methodology is amenable to the screening of sera from very large cohorts numbering in the thousands. When seroreactive and serodiagnostic antigen subsets from different infectious agents are printed onto the same array, the chip can discriminate between patients infected with different agents and also identify individuals with coinfections or multiple infections. We have shown that the individual proteins printed on these arrays capture antibodies present in serum from infected individuals and the amount of captured antibody can be quantified using fluorescent secondary antibody.

    In this way, a comprehensive profile of antibodies that result after infection or exposure can be determined that is characteristic of the type of infection and the stage of disease [9,10,31]. Here we summarize the approximate seroreactive and serodiagnostic antigens that were identified and published in 30 different organisms, and discuss the antibody response predictions from classification of reactive antigens based on functional and physical properties.

    Genes were amplified and cloned using a high-throughput PCR and recombination method [29].

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    Open reading frames from genomic DNA or cDNA were identified and amplified using gene-specific primers containing about 20 bp nucleotide extension complementary to ends of linearized pXT7 vector, which allows homologous recombination between the PCR product and pXT7 vector in competent Escherichia coli cells. Sera samples were diluted in E. Slides were incubated in biotin-conjugated secondary antibody Jackson ImmunoResearch and detected by incubation with streptavidin-conjugated SureLight P-3 Columbia Biosciences. Intensities were quantified.

    All signal intensities were corrected for spot-specific background. All foreground values were transformed and normalized using a robust linear model or nonlinear variance stabilizing normalization to remove systematic effects [24,34,35] Fig. Discovery of novel antigens associated with infectious diseases is fundamental to the development of serodiagnostic tests and protein subunit vaccines against existing and emerging pathogens.

    Systems Biology for Clinical Infectious Diseases Research Symposium

    Antigens differentially reactive among infected and healthy controls comprise even smaller percentage of the genome size: from 0. Full proteome microarrays were constructed for only a limited number of bacterial species; however, other data were published using partial arrays containing only partial proteome, and may over-represent the percentages of seroreactive and serodiagnostic antigens in the full proteome because the subset of proteins on the array was selected based on antigenic features seen previously. Another application for these empirical data is to train an algorithm to predict reactive antigens in silico , and several studies from our group apply enrichment analyses to identify proteomic features that tend to be seen more frequently in the seroreactive and serodiagnostic antigen sets [12,17,23].

    Efforts to predict antigenicity have relied on a few computational algorithms predicting signal peptide sequences signalP , transmembrane domains TMHMM , or subcellular localization Psort. The current database from this protein microarray approach contains quantitative antibody reactivity data against 40 proteins derived from 30 infectious microorganisms and more than 30 million data points derived from 15 patient sera.

    Interrogation of these data sets has revealed more than 10 proteomic features that are associated with antigenicity allowing an in-silico protein sequence and functional annotation-based approach to triage the least likely antigenic proteins from those that are more likely to be antigenic. These proteomic enrichment features Table 2 are: functionally annotated Clusters of Orthologous Groups of proteins U, M, N, and O or gene ontology function and process; computationally predicted features TMHMM, Signal peptide, pSort Outermembrane, pSort Periplasmic, and isoelectric point pI less than 5 for bacteria, and pI 7—9 for parasites ; and abundance of expression.

    Systems Biological Approaches in Infectious Diseases

    This approach applied to B. Parasite toxoplasma gondii proteins were assigned by gene ontology functions. Proteins involved in protein binding, catalytic activity, transporter activity, and transferase activity were significantly enriched [13]. Proteins with enzymatic activity other than kinase activity were enriched at 2. Proteins with gene ontology null functions, or involved in nucleotide and nucleic acid binding were underrepresented [13]. Proteins were also assigned by gene ontology process classification.

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    Proteins involved in ATP biosynthetic process were enriched. Several proteins involved in transport were also significantly enriched, including ion transport, protein transport, vesicle mediated transport, and other transport functions. Proteins involved in metabolic process, proteolysis, and signal peptide processing were also enriched. Conversely, proteins not assigned with gene ontology process categories were significantly underrepresented 0. The data set of Vaccinia viral proteins also allowed us to identify properties of viral proteins that were associated with immunogenicity.

    These predictors are strongest in MVA profiles, as the antibody profile to MVA is more heavily skewed toward structural proteins. In contrast, early proteins were underrepresented relative to the whole proteome, and there was negligible influence of molecular weight, pI, or the presence of a signal sequence on immunogenicity. Vaccinia antigens are either abundant components of MV particles, such as A10 and L4 [48] , or are expressed at high levels in infected cells, such as I1 and WR [49,50]. Their abundance may contribute to immunogenicity once released from infected cells, particularly if, like D13 [51] , such proteins have a propensity for self-assembly into macromolecular structures.