Biology subjects

Hopkins, R.

Publications and source records attributed to Hopkins, R..

4 recordsLinked to original sources

bioRxiv2018

DPP9 is an endogenous and direct inhibitor of the NLRP1 inflammasome that guards against human auto-inflammatory diseases

The inflammasome is a critical immune complex that activates IL-1 driven inflammation in response to pathogen- and danger-associated signals. Nod-like receptor protein-1 (NLRP1) is a widely expressed inflammasome sensor. Inherited gain-of-function mutations in NLRP1 cause a spectrum of human Mendelian diseases, including systemic autoimmunity and skin cancer susceptibility. However, its endogenous regulation and its cognate ligands are still unknown. Here we apply a proteomics screen to identify dipeptidyl dipeptidase, DPP9 as a novel interacting partner and a specific endogenous inhibitor of NLRP1 inflammasome in diverse primary cell types from human and mice. DPP9 inhibition via small molecule drugs, targeted mutations in its catalytic site and CRISPR/Cas9-mediated genetic deletion potently and specifically activate the NLRP1 inflammasome leading to pyroptosis and IL-1 processing via ASC and caspase-1. Mechanistically, DPP9 maintains NLRP1 in its monomeric, inactive state by binding to the auto-cleaving FIIND domain. NLRP1-FIIND is a self-sufficient DPP9 binding module and its disruption by a single missense mutation abrogates DPP9 binding and explains the aberrant inflammasome activation in NAIAD patients with arthritis and dyskeratosis. These findings uncover a unique peptidase enzyme-based mechanism of inflammasome regulation, and suggest that the DPP9-NLRP1 complex could be broadly involved in human inflammatory disorders.

immunology↗

bioRxiv2017

Variation in context dependent foraging behavior across pollinators

Pollinator foraging behavior has direct consequences for plant reproduction and has been implicated in driving floral trait evolution. Exploring the degree to which pollinators exhibit flexibility in foraging behavior will add to a mechanistic understanding of how pollinators can impact selection on plant traits. Although plants have evolved suites of floral traits to attract pollinators, flower color is a particularly important aspect of the floral display. Some pollinators show strong innate color preference, but many pollinators display flexibility in preference due to learning associations between rewards and color, or due to variable perception of color in different environments or plant communities. This study examines the flexibility in flower color preference of two groups of native butterfly pollinators under natural field conditions. Our study reveals that pipevine swallowtails and skippers, the predominate pollinators of the two native Texas Phlox species, display distinct patterns of color preferences across different contexts. Pipevine swallowtails exhibit highly flexible color preferences and likely utilize other floral traits to make foraging decisions. In contrast, skippers have consistent color preferences and likely use flower color as a primary cue for foraging. As a result of this variation in color preference flexibility, the two pollinator groups impose concordant selection on flower color in some contexts but discordant selection in other contexts. This variability could have profound implications for how flower traits respond to pollinator-mediated selection. Our findings suggest that studying dynamics of behavior in natural field conditions is important for understanding plant-pollinator interactions.

animal behavior and cognition↗

bioRxiv2017

Correlated evolution of self and interspecific incompatibly across the range of a Texas wildflower

Plant species have repeatedly evolved recognition systems between pollen and pistils that identify and reject inappropriate matings. Two of the most important systems recognize self-pollen and interspecific pollen. Outstanding questions are whether and how these two recognition systems are linked and if this association could constrain the evolution of mate choice. Our study characterizes variation in self and interspecific incompatibility in the native range of the Texas wildflower Phlox drummondii. We found quantitative variation in self-incompatibility and demonstrate that this variation is significantly correlated with variation in incompatibility with its close congener P. cuspidata. Furthermore, we find strong evidence that self and interspecific incompatibility involve common mechanisms of pollen adhesion or early pollen-tube germination. Finally, we show that P. drummondii populations that co-occur and hybridize with P. cuspidata have significantly higher interspecific incompatibility and self-incompatibility than isolated P. drummondii populations. This geographic variation suggests that the evolution of self-compatibility is constrained by selection favoring interspecific incompatibility to reduce maladaptive hybridization. To our knowledge this is the strongest evidence that a correlation between variation in self and interspecific incompatibilities could influence the evolution of pollen recognition across the range of a species.

plant biology↗

bioRxiv2016

Quantifying the relationship between pollinator behavior and plant reproductive isolation

Pollinator behavior is an important contributor to reproductive isolation in plants. Despite hundreds of years of empirical research, we lack a quantitative framework for evaluating how variation in pollinator behavior causes variation in reproductive isolation in plants. Here I present a model describing how two aspects of pollinator behavior - constancy and preference - lead to reproductive isolation in plants. This model is motivated by two empirical observations: most co-occurring plants vary in frequency over space and time and most plants have multiple pollinators that differ in behavior. These two observations suggest a need to understand how plant frequency and pollinator frequency influence reproductive isolation between co-occurring plants. My model predicts how the proportion of heterospecific matings varies over plant frequencies given pollinator preference and constancy. I find that the shape of this relationship is dependent on the strength of pollinator behavior. Additionally, my model incorporates multiple pollinators with different behaviors to predict the proportion of heterospecific matings across pollinator frequencies. I find that when two pollinators display different strength constancy the total proportion of heterospecific matings is simply the average proportion of heterospecific matings predicted for each pollinator. When pollinators vary in their preference the pollinator with the stronger preference disproportionally contributes to the predicted proportion of total heterospecific matings. I apply this model to examples of pollinator-mediated reproductive isolation in Phlox and in Mimulus to predict relationships between plant and pollinator frequency and reproductive isolation in natural systems.

evolutionary biology↗