Seattle, WA, United States

Seattle Biomedical Research Institute
Seattle, WA, United States

Seattle BioMed, known prior to 2010 as Seattle Biomedical Research Institute or SBRI, is the largest independent, non-profit organization in the United States focused solely on infectious disease discovery research. The mission of Seattle BioMed's 360+ employees is to eliminate the world's most devastating infectious diseases through leadership in scientific discovery. Seattle BioMed is headquartered and has research labs in the South Lake Union area of Seattle, WA. Seattle BioMed's research focuses on four areas of infectious disease: HIV/AIDS, malaria, tuberculosis , and Emerging & Neglected Diseases like African sleeping sickness, leishmaniasis, Chagas disease, and toxoplasmosis. Seattle BioMed is engaged in early stages of the scientific pipeline including bench science and malaria clinical trials and has expertise in immunology, vaccinology, and drug discovery. Wikipedia.

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Seattle Biomedical Research Institute | Date: 2015-05-07

The present disclosure provides for methods of addressing the devastating effects of malaria infection by mosquito-borne Plasmodium parasites. The methods include the administration of an effective amount of at least one pro-apoptotic agent and the administration of an effective amount of at least one p53 activator. The at least one pro-apoptotic agent can be administered concurrently with, prior to, or subsequent to the at least one p53 activator. The at least one pro-apoptotic agent and/or at least one p53 activator can be administered concurrently with, prior to, or subsequent to exposure of a hepatocyte (in vivo or in vitro) by a Plasmodium parasite. In some embodiments, the administration of the at least one pro-apoptotic agent combined with the administration of the at least one p53 activator results in clearance of hypnozoite stage of P. vivax or P. ovale, and thus prevents relapse of symptoms and disease from the infection of these parasites.

Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.1.4-4 | Award Amount: 40.88M | Year: 2011

Vaccines so far have been developed mostly by following an empiric approach. To prevent and possibly cure unresolved and emerging infectious diseases we need to fully exploit the potential of the human immune system. Progress in science and technology makes it possible to achieve what was previously deemed impossible. The scope of this project is to produce knowledge necessary to develop novel and powerful immunization technologies for the next generation of human vaccines. This goal requires a multidisciplinary approach in which diverse but complementary scientific disciplines and technologies converge. Therefore some of the most competitive European research groups from public institutions and biotechs have agreed to join forces in ADITEC, together with top US groups on systems biology and adjuvants to support this enterprise. A systems biology approach will be used to study licensed and experimental vaccines in patient characterization studies and in clinical trials, to investigate the effect of adjuvants, vectors, formulations, delivery devices, routes of immunization, homologous and heterologous primeboost schedules, as well as the impact of host factors such as age, gender, genetics and pathologies. Animal models will be used to complement human studies, and to select novel immunization technologies to be advanced to the clinic. To address these issues in a coordinated manner, ADITEC is organised on a matrix structure in which research themes and experimental approaches feed into each other. Training curricula will be created to impact on the formation of the next generation of EU researchers in the field. ADITEC scientists and institutions are part of the Sclavo Vaccines Association (SVA), which is dedicated to vaccines and vaccine research. SVA, acting as the coordinating institution, guarantees the long-term commitment and sustainability of this initiative, beyond the duration of ADITEC itself.

Aitchison J.D.,Seattle Biomedical Research Institute | Rout M.P.,Rockefeller University
Genetics | Year: 2012

Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cell's genome. This exchange requires a dedicated transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear envelope and composed of proteins termed nucleoporins (or "Nups"), and (2) nuclear transport factors that recognize the cargoes to be transported and ferry them across the NPCs. This transport is regulated at multiple levels, and the NPC itself also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Here we summarize how the yeast Saccharomyces has been used extensively as a model system to understand the fundamental and highly conserved features of this transport system, revealing the structure and function of the NPC; the NPC's role in the regulation of gene expression; and the interactions of transport factors with their cargoes, regulatory factors, and specific nucleoporins. © 2012 by the Genetics Society of America.

Sherman D.R.,Seattle Biomedical Research Institute | Gagneux S.,University of Basel
Nature Genetics | Year: 2011

Current models of Mycobacterium tuberculosis latency presume very low mycobacterial replication and mutation rates. In contrast to these models, a study reporting whole-genome sequencing of mycobacteria isolated from infected macaques shows that the mutational capacity of M. tuberculosis during latency is not reduced, a finding with important implications for tuberculosis research and control. © 2011 Nature America, Inc. All rights reserved.

Tam V.C.,Seattle Biomedical Research Institute
Seminars in Immunology | Year: 2013

Bioactive lipid mediators play crucial roles in promoting the induction and resolution of inflammation. Eicosanoids and other related unsaturated fatty acids have long been known to induce inflammation. These signaling molecules can modulate the circulatory system and stimulate immune cell infiltration into the site of infection. Recently, DHA- and EPA-derived metabolites have been discovered to promote the resolution of inflammation, an active process. Not only do these molecules stop the further infiltration of immune cells, they prompt non-phlogistic phagocytosis of apoptotic neutrophils, stimulating the tissue to return to homeostasis. After the rapid release of lipid precursors from the plasma membrane upon stimulation, families of enzymes in a complex network metabolize them to produce a large array of lipid metabolites. With current advances in mass spectrometry, the entire lipidome can be accurately quantified to assess the immune response upon microbial infection. In this review, we discuss the various lipid metabolism pathways in the context of the immune response to microbial pathogens, as well as their complex network interactions. With the advancement of mass spectrometry, these approaches have also been used to characterize the lipid mediator response of macrophages and neutrophils upon immune stimulation in vitro. Lastly, we describe the recent efforts to apply systems biology approaches to dissect the role of lipid mediators during bacterial and viral infections in vivo. © 2013 Elsevier Ltd.

Zak D.E.,Seattle Biomedical Research Institute | Tam V.C.,Seattle Biomedical Research Institute | Aderem A.,Seattle Biomedical Research Institute
Annual Review of Immunology | Year: 2014

Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology. © 2014 by Annual Reviews. All rights reserved.

Smith J.J.,Institute for Systems Biology | Aitchison J.D.,Seattle Biomedical Research Institute
Nature Reviews Molecular Cell Biology | Year: 2013

Peroxisomes carry out various oxidative reactions that are tightly regulated to adapt to the changing needs of the cell and varying external environments. Accordingly, they are remarkably fluid and can change dramatically in abundance, size, shape and content in response to numerous cues. These dynamics are controlled by multiple aspects of peroxisome biogenesis that are coordinately regulated with each other and with other cellular processes. Ongoing studies are deciphering the diverse molecular mechanisms that underlie biogenesis and how they cooperate to dynamically control peroxisome utility. These important challenges should lead to an understanding of peroxisome dynamics that can be capitalized upon for bioengineering and the development of therapies to improve human health. © 2013 Macmillan Publishers Limited. All rights reserved.

Mikolajczak S.A.,Seattle Biomedical Research Institute
Molecular Therapy | Year: 2014

Immunization with live-attenuated Plasmodium sporozoites completely protects against malaria infection. Genetic engineering offers a versatile platform to create live-attenuated sporozoite vaccine candidates. We previously generated a genetically attenuated parasite (GAP) by deleting the P52 and P36 genes in the NF54 wild-type (WT) strain of Plasmodium falciparum (Pf p52-/p36- GAP). Preclinical assessment of p52-/p36- GAP in a humanized mouse model indicated an early and severe liver stage growth defect. However, human exposure to >200 Pf p52-/p36- GAP-infected mosquito bites in a safety trial resulted in peripheral parasitemia in one of six volunteers, revealing that this GAP was incompletely attenuated. We have now created a triple gene deleted GAP by additionally removing the SAP1 gene (Pf p52-/p36-/sap1- GAP) and employed flippase (FLP)/flippase recognition target (FRT) recombination for drug selectable marker cassette removal. This next-generation GAP was indistinguishable from WT parasites in blood stage and mosquito stage development. Using an improved humanized mouse model transplanted with human hepatocytes and human red blood cells, we show that despite a high-dose sporozoite challenge, Pf p52-/p36-/sap1- GAP did not transition to blood stage infection and appeared to be completely attenuated. Thus, clinical testing of Pf p52-/p36-/sap1- GAP assessing safety, immunogenicity, and efficacy against sporozoite challenge is warranted.Molecular Therapy (2014); doi:10.1038/mt.2014.85.

Seattle Biomedical Research Institute and University of Queensland | Date: 2013-12-10

The present disclosure relates to biofragment compositions that comprise bioparticle fragments and at least one heterologous antigen-binding molecule. In some embodiments, the biofragment is typically derived from a larger, intact bioparticle that express the at least one heterologous antigen-binding molecule at the surface, and the biofragment has increased solubility to facilitate assays for antigen detection. The disclosure also relates the related methods of using and making the biofragment compositions, as well as systems and devices implementing the biofragment compositions. In some embodiments, the related methods, systems and devices do not require additional detection reagents, such as animal derived detection antibodies.

University of Washington and Seattle Biomedical Research Institute | Date: 2015-07-15

Disclosed are compositions and methods for detecting the presence of viable cells in a sample. Included are compositions and methods for increasing the sensitivity of a nucleic acid amplification test for determining the presence of at least one target microorganism in a sample. Also disclosed are compositions and methods for detecting ribosomal RNA precursors (pre-rRNA) as dynamic indicators of viable microorganisms in a sample.

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