Biology subjects

Lamy, L.

Publications and source records attributed to Lamy, L..

4 recordsLinked to original sources

bioRxiv2023

Life history traits, pace-of-life and dispersal among and within five species of Trichogramma wasps: a comparative analysis

Major traits defining the life history of organisms are often not independent from each other, with most of their variation aligning along key axes such as the pace-of-life axis. We can define a pace-of-life axis structuring reproduction and development time as a continuum from less-fecund, longer-developing slow types to more-fecund, shorter-developing fast types. Such axes, along with their potential associations or syndromes with other traits such as dispersal, are however not universal; in particular, support for their presence may be taxon and taxonomic scale-dependent. Knowing about such life-history strategies may be especially important for understanding eco-evolutionary dynamics, as these trait syndromes may constrain trait variation or be correlated with other traits. To understand how life-history traits and effective dispersal covary, we measured these traits in controlled conditions for 28 lines from five species of Trichogramma, which are small endoparasitoid wasps frequently used as a biological model in experimental evolution but also in biocontrol against Lepidoptera pests. We found partial evidence of a pace-of-life axis at the interspecific level: species with higher fecundity also had faster development time. However, faster-developing species also were more likely to delay egg-laying, a trait that is usually interpreted as "slow". There was no support for similar covariation patterns at the within-species line level. There was limited variation in effective dispersal between species and lines, and accordingly, we did not detect any correlation between effective dispersal probability and life-history traits. We discuss how expanding our experimental design by accounting for the density-dependence of both the pace of life and dispersal might improve our understanding of those traits and how they interact with each other. Overall, our results highlight the importance of exploring covariation at the "right" taxonomic scale, or multiple taxonomic scales, to understand the (co)evolution of life-history traits. They also suggest that optimizing both reproductive and development traits to maximize the efficiency of biocontrol may be difficult in programs using only one species.

ecology↗

bioRxiv2022

In vivo quantitative high-throughput screening for drug discovery and comparative toxicology

Quantitative high-throughput screening (qHTS) evaluates the pharmacology of drug and investigational agent libraries for potential therapeutic uses, toxicological risk assessment, and increasingly for academic chemical tool discovery. Phenotypic HTS assays aim to interrogate molecular pathways and networks, often relying on cell culture systems, historically with less emphasis on multicellular organisms. C. elegans has served as a powerful eukaryotic model organism for human biology and disease by virtue of genetic conservation and experimental tractability. Here we describe a paradigm to enable C. elegans in qHTS using 384-well microtiter plate laser scanning cytometry. GFP-expressing organisms are used to reveal phenotype-modifying structure-activity relationships to guide subsequent life stages and proteomic analysis. E. coli bacterial ghosts, a non-replicating nutrient source, allow compound exposures over 7-days spanning two life cycles to mitigate complications from bacterial overgrowth. We demonstrate the method with a library composed of anti-infective agents, or molecules of general toxicological concern. Each was tested in 7-point titration to assess the feasibility of nematode-based in vivo qHTS, and examples of follow-up strategies were provided to study organism-based chemotype selectivity and subsequent network perturbations having a physiological impact. We anticipate a broader application of this qHTS-coupled proteomics approach will enable the analysis of C. elegans orthologous transgenic phenotypes of human pathologies to facilitate drug and probe profiling from high-impact chemical libraries for a range of therapeutic indications and study of potential toxicological signatures. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/505462v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@7ef320org.highwire.dtl.DTLVardef@8bc35corg.highwire.dtl.DTLVardef@1c6f446org.highwire.dtl.DTLVardef@cf56f1_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2020

Genetics of nodulation in Aeschynomene evenia uncovers new mechanisms of the rhizobium-legume symbiosis

Among legumes (Fabaceae) capable of nitrogen-fixing nodulation, several Aeschynomene spp. use a unique symbiotic process that is independent of Nod factors and infection threads. They are also distinctive in developing root and stem nodules with photosynthetic bradyrhizobia. Despite the significance of these symbiotic features, their understanding remains limited. To overcome such limitations, we conducted genetic studies of nodulation in Aeschynomene evenia, supported by the development of a genome sequence for A. evenia and transcriptomic resources for 10 additional Aeschynomene spp. Comparative analysis of symbiotic genes substantiated singular mechanisms in the early and late nodulation steps. A forward genetic screen also showed that AeCRK, coding a novel receptor-like kinase, and the symbiotic signaling genes AePOLLUX, AeCCamK, AeCYCLOPS, AeNSP2 and AeNIN, are required to trigger both root and stem nodulation. This work demonstrates the utility of the A. evenia model and provides a cornerstone to unravel new mechanisms underlying the rhizobium-legume symbiosis.

plant biology↗

bioRxiv2019

A Homogeneous SIRPα-CD47 Cell-Based, Ligand-Binding Assay: Utility for Small Molecule Drug Development in Immuno-oncology.

CD47 is an immune checkpoint protein that downregulates both the innate and adaptive anti-tumor immune response via its counter receptor SIRP. Biologics, including humanized CD47 monoclonal antibodies and decoy SIRP receptors, that block the SIRP-CD47 interaction, are currently being developed as cancer immunotherapy agents. However, adverse side effects and limited penetration of tumor tissue associated with their structure and large size may impede their clinical application. We recently developed a quantitative high throughput screening assay platform to identify small molecules that disrupt the binding of SIRP and CD47 as an alternative approach to these protein-based therapeutics. Here, we report on the development and optimization of a cell-based binding assay to validate active small molecules from our biochemical screening effort. This assay has a low volume, high capacity homogenous format that relies on laser scanning cytometry (LSC) and associated techniques to enhance signal to noise measurement of cell surface binding. The LSC assay is specific, concentration dependent, and validated for the two major human SIRP variants (V1 and V2), with results that parallel those of our biochemical data as well as published studies. The LSC assay also confirmed published studies, such as the inhibition of amino-terminal pyroglutamate formation in CD47 disrupts SIRP binding. SIRP-CD47 interaction could be quantitatively measured in live and fixed tumor cells. Use of fixed cells reduces the burden of cell maintenance and provides stable cell standards to control for inter- and intra-assay variations. We also demonstrate the utility of the assay to characterize the activity of the first reported small molecule antagonists of the SIRP-CD47 interaction. This assay will support the screening of thousands of compounds to identify or validate active small molecules as hits, develop structure activity relationships and assist in the optimization of hits to leads by a typical iterative medicinal chemistry campaign.

immunology↗