Biology subjects

Davidson, D.

Publications and source records attributed to Davidson, D..

10 recordsLinked to original sources

bioRxiv2026

Molecular characterization of the effector-immunity pair Rhs2-SciX from Salmonella Typhimurium

The type VI secretion system (T6SS) is a dynamic nanomachine used by bacteria to compete for space and nutrients. To kill rival bacteria, the T6SS secretes toxic effector proteins directly into adjacent cells in a contact-dependent manner. Effectors have diverse biochemical functions that arise from subtle structural modifications to related enzyme folds. To protect from self-intoxication, effectors are encoded with a cognate immunity protein in effector-immunity pairs. Immunity proteins inhibit toxicity by directly binding the effector active site and are as structurally diverse as their effectors. Salmonella Typhimurium has several known effectors of diverse biochemical functions, however the effector-immunity pair Rhs2-SciX remains largely unstudied. Here, we take a structural approach and show that Rhs2 is a BECR family nuclease through modeling and toxicity assays. Furthermore, we solve an X-ray crystal structure of SciX and study the solution-state properties of the immunity protein to gain insight into the binding and inhibition mechanism of Rhs2. Finally, we discover that Rhs2 binds directly to EF-Tu suggesting that Rhs2 inhibits translation to cause cell death. Our work probes the structure and function of the effector-immunity pair Rhs2-SciX, demonstrates the biochemical diversity of Salmonella T6SS effectors, and highlights the conserved T6SS toxicity strategy of binding EF-Tu.

biochemistry↗

bioRxiv2025

Binding of inhibitory checkpoints to CD18 in cis hinders anti-cancer immune responses

SIRP is an inhibitory receptor on macrophages that limits phagocytosis and anti-tumor activity of macrophages by "trans" interacting with CD47 on tumor cells. Herein, we found that a large component of SIRPs inhibitory function occurred independently of CD47-binding and phosphatase signaling. This function resulted from a direct interaction between SIRP and CD18 ({beta}2 integrin) in "cis" at the surface of macrophages, involving SIRP amino acids distinct from those implicated in the SIRP-CD47 interaction. The cis interaction prevented activation of CD18, which is necessary for phagocytosis. Combined blockade of SIRP-CD18 and SIRP-CD47 was essential for maximizing phagocytosis and suppression of tumor growth in vivo. Similar cis interactions between CD18 and other inhibitory checkpoints, including PD-1, were also observed. Thus, in addition to mediating effects when engaged by ligands in trans, inhibitory checkpoints suppress immune cell activation through a mechanism targeting CD18 in cis. This dual mode of action should be considered when developing blockers of inhibitory checkpoints for immunotherapy. One-Sentence SummaryIn addition to being engaged in "trans" by ligands on tumor cells, inhibitory receptors, such as SIRP and PD-1, hinder anti-cancer immune responses by "cis" interacting with {beta}2 integrin CD18.

immunology↗

bioRxiv2024

Non-additive dosage-dependent effects of TaGS3 gene editing on grain size and weight in wheat

The grain size in cereals is one of the main component traits contributing to yield. Previous studies showed that loss-of-function (LOF) mutations in GS3, encoding G{gamma} subunit of the multimeric G protein complex, increase grain size and weight in rice. While association between allelic variation in GS3 homologs of wheat and grain weight/size was detected previusly, the effects of LOF alleles on these traits remain unknown. We used genome editing to create the TaGS3 mutant lines with the LOF homeo-allele dosage variation. Contrary to results obtained for rice, editing of all three TaGS3 copies result in significant decrease in grain length, width, grain area and weight, without affecting number of grains per spike. Compared to wild type, the highest increase in grain weight and area was observed in mutants with the intermediate dosage of the LOF alleles, indicating that suppressive effects of TaGS3 on grain size and weight in wheat are dosage-dependent and non-additive. Our results suggest that TaGS3 likely represents a functionally diverged homolog of GS3 evolved in the wheat lineage. The newly developed LOF alleles of TaGS3 expand the set of CRISPR-Cas9-induced variants of yield component genes that could be used for increasing grain weight in wheat.

genetics↗

bioRxiv2024

Ecogeographic signals of local adaptation in a wild relative help to identify variants associated with improved wheat performance under drought stress

Prioritizing wild relative diversity for improving crop adaptation to emerging drought-prone environments is challenging. Here, we combined the genome-wide environmental scans (GWES) in wheat diploid ancestor Aegilops tauschii with allele testing in the genetic backgrounds of adapted cultivars to identify new diversity for improving wheat adaptation to water-limiting conditions. Evaluation of adaptive allele effects was carried out in Ae. tauschii-wheat introgression lines (ILs) phenotyped for multiple agronomic traits under irrigated and water-limiting conditions using both UAS-based imaging and conventional approaches. The GWES showed that climatic gradients alone explain most (57.8%) of genomic variation in Ae. tauschii, with many alleles associated with climatic factors in Ae. tauschii being linked with improved performance of ILs under water-limiting conditions. The most significant GWES SNP located on chromosome 4D and associated with temperature annual range was linked with reduced canopy temperature in ILs. Our results suggest that (i) introgression of climate-adaptive alleles from Ae. tauschii have potential to improve wheat performance under water-limiting conditions, (ii) variants controlling physiological processes responsible for maintaining leaf temperature are likely among the targets of adaptive selection in a wild relative, and (iii) adaptive variation uncovered by GWES in wild relatives has potential to improve climate resilience of crop varieties.

genetics↗

bioRxiv2024

The Streptococcus phage protein paratox is an intrinsically disordered protein.

The bacteriophage protein paratox blocks quorum sensing in its streptococcal host by directly binding the signal receptor and transcription factor ComR. This reduces ability of Streptococcus to uptake environmental DNA and protects phage DNA from damage by recombination. Past work characterizing the paratox:ComR molecular interaction revealed that paratox adopts a well-ordered globular fold when bound to ComR. However, solution-state biophysical measurements suggested that paratox may be conformationally dynamic. To address this discrepancy, we investigated the stability and dynamic properties of paratox in solution using circular dichroism, nuclear magnetic resonance, and several fluorescence-based protein folding assays. Our work shows that under dilute buffer conditions paratox is intrinsically disordered. We also show that the addition of kosmotropic salts or protein stabilizing osmolytes induces paratox folding. However, only the addition of ComR was able to induce paratox to adopt its previously characterized globular fold. Furthermore, as we can induce different paratox folding-states we characterize Prx folding thermodynamics and folding kinetics using stopped flow measurements. Based upon the kinetic results, paratox is a highly dynamic protein in dilute solution, folding and refolding within the 10 ms timescale. Overall, our results demonstrate that the streptococcal phage protein paratox is an intrinsically disordered protein in a two-state equilibrium with a solute-stabilized folded form. Furthermore, the solute-stabilized paratox fold is likely the predominant form of paratox in a solute-crowded bacterial cell. Finally, our work suggests that Prx binds and inhibits ComR, and thus quorum sensing in Streptococcus, by a combination of conformational selection and induced-fit binding mechanisms.

biochemistry↗

bioRxiv2022

De novo assembly and annotation of the Patagonian toothfish (Dissostichus eleginoides) genome

Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae, found at depths between 70 and 2,500 meters on the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. Genomic sequence data for this species is limited. Here, we report a high-quality assembly and annotation of the D. eleginoides genome, generated using a combination of Illumina, PacBio and Omni-C sequencing technologies. To aid the genome annotation, the transcriptome derived from a variety of toothfish tissues was also generated using both short and long read sequencing methods. The final genome assembly was 797.8 Mb with a N50 scaffold length of 3.5 Mb. Approximately 31.7% of the genome consisted of repetitive elements. A total of 35,543 putative protein-coding regions were identified, of which 50% have been functionally annotated. Transcriptomics analysis showed that approximately 64% of the predicted genes (22,617 genes) were found to be expressed in the tissues sampled. Comparative genomics analysis revealed that the anti-freeze glycoprotein (AFGP) locus of D. eleginoides does not contain any AFGP proteins compared to the same locus in the Antarctic toothfish (Dissostichus mawsoni). This is in agreement with previously published results looking at hybridization signals and confirms that Patagonian toothfish do not possess AFGP coding sequences in their genome. The high-quality genome assembly of the Patagonian toothfish will provide a valuable genetic resource for ecological and evolutionary studies on this and other closely related species.

genomics↗

bioRxiv2021

The haplotype-based analysis of Aegilops tauschii introgression into hard red winter wheat and its impact on productivity traits

Introgression from wild relatives have a great potential to broaden beneficial allelic diversity available for crop improvement in breeding programs. Here, we assessed the impact of introgression from 21 diverse accessions of Aegilops tauschii, the diploid ancestor of the wheat D genome, into six hard red winter wheat cultivars on yield and yield component traits. We used 5.2 million imputed D genome SNPs identified by whole-genome sequencing of parental lines and the sequence-based genotyping of introgression population including 351 BC1F3:5 lines. Phenotyping data collected from the irrigated and non-irrigated field trials revealed that up to 23% of the introgression lines produce more grain than the parents and check cultivars. Based on sixteen yield stability statistics, the yield of twelve introgression lines (3.4%) was stable across treatments, years and locations; five of these lines were also high yielding, producing 9.8% more grain than the average yield of check cultivars. The most significant SNP-trait and haplotype-trait associations were identified on chromosome arms 2DS and 6DL for spikelet number per spike (SNS), on chromosome arms 2DS, 3DS, 5DS and 7DS for grain length and on chromosome arms 1DL, 2DS, 6DL and 7DS for grain width. Introgression of haplotypes from Ae. tauschii parents was associated with increase in SNS, which positively correlated with heading date, whereas haplotypes from hexaploid wheat parents were associated with increased grain width. We show that haplotypes on 2DS associated with increased spikelet number and heading date are linked with multiple introgressed alleles of Ppd-D1 identified by the whole-genome sequencing of the Ae. tauschii parents. While some introgressed haplotypes exhibited significant pleiotropic effects with the direction of effects on the yield component traits being largely consistent with the previously reported trade-offs, there were haplotype combinations associated with the positive trends in yield. The characterized repertoire of the introgressed haplotypes derived from Ae. tauschii accessions with the combined positive effects on yield and yield components traits in elite germplasm provides a valuable source of alleles for improving the productivity of winter wheat by optimizing the contribution of component traits to yield.

genetics↗

bioRxiv2018

The Portal Project: a long-term study of a Chihuahuan desert ecosystem

This is a data paper for the Portal Project, a long-term ecological study of rodents, plants, and ants located in southeastern Arizona, U.S.A. This paper contains an overview of methods and information about the structure of the data files and the relational structure among the files. This is a living data paper and will be updated with new information as major changes or additions are made to the data. All data - along with more detailed data collection protocols and site information - is archived at: https://doi.org/10.5281/zenodo.1215988.

ecology↗

bioRxiv2018

Gene editing and mutagenesis reveal inter-cultivar differences and additivity in the contribution of TaGW2 homoeologues to grain size and weight in wheat

The TaGW2 gene homoeologues have been reported to be negative regulators of grain size (GS) and thousand grain weight (TGW) in wheat. However, the contribution of each homoeologue to trait variation among different wheat cultivars is not well documented. We used the CRISPR-Cas9 system and TILLING to mutagenize each homoeologous gene copy in cultivars Bobwhite and Paragon, respectively. Plants carrying single-copy nonsense mutations in different genomes showed different levels of GS/TGW increase, with TGW increasing by an average of 5.5% (edited lines) and 5.3% (TILLING mutants). In any combination, the double homoeologue mutants showed higher phenotypic effects than the respective single-genome mutants. The double mutants had on average 12.1% (edited) and 10.5% (TILLING) higher TGW with respect to wild-type lines. The highest increase in GS and TGW was shown for triple mutants of both cultivars, with increases of 16.3% (edited) and 20.7% (TILLING) in TGW. The additive effects of the TaGW2 homoeologues were also demonstrated by the negative correlation between the functional gene copy number and GS/TGW in Bobwhite mutants and an F2 population. The highest single-genome increases in GS and TGW in Paragon and Bobwhite were obtained by mutations in the B and D genomes, respectively. These inter-cultivar differences in the phenotypic effects between the TaGW2 gene homoeologues coincide with inter-cultivar differences in the homoeologue expression levels. These results indicate that GS/TGW variation in wheat can be modulated by the dosage of homoeologous genes with inter-cultivar differences in the magnitude of the individual homoeologue effects.

genetics↗

bioRxiv2017

Is the LAN effect in morphosyntactic processing an ERP artifact?

The left anterior negativity (LAN) is an ERP component that has been often associated with morphosyntactic processing, but recent reports have questioned whether the LAN effect, in fact, exists. The present project examined whether the LAN effect, observed in the grand average response to local agreement violations, is the result of the overlap between two different ERP effects (N400, P600) at the level of subjects (n=80), items (n=120), or trials (n=6160). By-subject, by-item, and by-trial analyses of the ERP effect between 300 and 500 ms showed a LAN for 55% of the participants, 46% of the items, and 49% of the trials. Many examples of the biphasic LAN-P600 response were observed. Mixed-linear models showed that the LAN effect size was not reduced after accounting for subject variability. The present results suggest that there are cases where the grand average LAN effect represents the brain responses of individual participants, items, and trials.

neuroscience↗