Global change drivers and the risk of infectious disease

Anthropogenic change is contributing to the rise in emerging infectious diseases, but it remains unclear which global change drivers most increase disease and under what contexts. We amassed a dataset from the literature that includes 1,832 observations of infectious disease responses to global change drivers across 1,202 host-parasite combinations. We found that biodiversity loss, climate change, and introduced species were associated with increases in disease-related endpoints or harm (i.e., enemy release for introduced species), whereas urbanization was associated with decreases in disease endpoints. Natural biodiversity gradients, deforestation, forest fragmentation, and most classes of chemical contaminants had non-significant effects on these endpoints. Overall, these results were consistent across human and non-human diseases. Context-dependent effects of the global change drivers on disease were common and are discussed. These findings will help better target disease management and surveillance efforts towards global change drivers that increase disease.One-Sentence SummaryHere we quantify which global change drivers increase infectious diseases the most to better target global disease management and surveillance efforts

Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies

Heavy chain-only antibodies (HCAbs) do not associate with light chains and their VH regions are functional as single domains, forming the smallest active antibody fragment. These VH regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human VH regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human VH domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules

Knox et al. data

Full dataset for Knox et al. (2017) Ecology Letter

Autonomous year-round sampling and sensing to explore the physical and biological habitability of permanently ice-covered antarctic lakes

© 2014, Asociacion Geologica Argentina. All rights reserved. The lakes of the McMurdo Dry Valleys, Antarctica, are some of the only systems on our planet that are perennially ice-covered and support year-round metabolism. As such, these ecosystems can provide important information on conditions and life in polar regions on Earth and on other icy worlds in our solar system.Working in these extreme environments of the Dry Valleys poses many challenges, particularly with respect to data collection during dark winter months when logistical constraints make fieldwork difficult. In this paper, we describe the motivation, design, and challenges for this recently deployed instrumentation in Lake Bonney, a lake that has been the subject of summer research efforts for more than 40 years. The instrumentation deployed includes autonomous water, phytoplankton, and sediment samplers as well as cable-mounted profiling platforms with dissolved gas and fluorometry sensors. Data obtained from these instruments will allow us, for the first time, to define the habitability of this environment during the polar night. We include lessons learned during deployment and recommendations for effective instrument operation in these extreme conditions

Microbial Community Responses to Increased Water and Organic Matter in the Arid Soils of the McMurdo Dry Valleys, Antarctica

The soils of the McMurdo Dry Valleys, Antarctica are an extreme polar desert, inhabited exclusively by microscopic taxa. This region is on the threshold of anticipated climate change, with glacial melt, permafrost thaw, and the melting of massive buried ice increasing liquid water availability and mobilizing soil nutrients. Experimental water and organic matter (OM) amendments were applied to investigate how these climate change effects may impact the soil communities. To identify active taxa and their functions, total community RNA transcripts were sequenced and annotated, and amended soils were compared with unamended control soils using differential abundance and expression analyses. Overall, taxonomic diversity declined with amendments of water and organic matter. The domain Bacteria increased with both amendments while Eukaryota declined from 38% of all taxa in control soils to 8% and 11% in water and OM amended soils, respectively. Among bacterial phyla, Actinobacteria (59%) dominated water-amended soils and Firmicutes (45%) dominated OM amended soils. Three bacterial phyla (Actinobacteria, Proteobacteria, and Firmicutes) were primarily responsible for the observed positive functional responses, while eukaryotic taxa experienced the majority (27 of 34) of significant transcript losses. These results indicated that as climate changes in this region, a replacement of endemic taxa adapted to dry, oligotrophic conditions by generalist, copiotrophic taxa is likely

Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies

We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest

Image_1_Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies.jpeg

<p>We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.</p

Image_2_Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies.jpeg

<p>We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.</p