Biology subjects

Gracia, P.

Publications and source records attributed to Gracia, P..

3 recordsLinked to original sources

bioRxiv2022

Multi-environment genome-wide association mapping of culm morphology traits in barley

In cereals with hollow internodes, lodging resistance is influenced by morphological characteristics such as internode diameter and culm wall thickness. Despite their relevance, knowledge of the genetic control of these traits and their relationship with lodging is lacking in temperate cereals such as barley. To fill this gap, we developed an image-analysis based protocol to accurately phenotype culm diameter and culm wall thickness across 261 barley accessions. Analysis of culm trait data collected from field trials in 7 different environments revealed genetic control as supported by high heritability values, as well as genotype-by-environment interactions. The collection was structured mainly according to row-type, which had a confounding effect on culm traits as evidenced by phenotypic correlations. In addition, culm traits showed strong negative correlations with lodging but weak correlations with plant height across row-types, indicating the possibility of improving lodging resistance independent of plant height. Using 50k iSelect SNP genotyping data, we conducted multi-environment genome-wide association studies using mixed model approach across the whole panel and row-type subsets: we identified a total of 192 QTLs for the studied traits, including subpopulation-specific QTLs and several main effect loci for culm traits showing negative effects on lodging without impacting plant height. Providing first insights into the genetic architecture of culm morphology in barley and the possible role of candidate genes involved in hormone and cell wall related pathways, this work supports the potential of loci underpinning culm features to improve lodging resistance and increase barley yield stability under changing environments. One-sentence summaryGenetic analysis of a diverse collection of European barleys reveals genomic regions underpinning stem morphological features associated with lodging resistance.

plant biology↗

bioRxiv2021

α-Helical peptidic scaffolds to target α-synuclein pathogenic species with high affinity and selectivity.

-Synuclein aggregation is a key driver of neurodegeneration in Parkinsons disease and related syndromes. Accordingly, obtaining a molecule that targets -synuclein pathogenic assemblies with high affinity and selectivity is a long-pursued objective. Here, we have exploited the biophysical properties of toxic oligomers and amyloid fibrils to identify a family of -helical peptides that bind selectively to these -synuclein species with low nanomolar affinity, without interfering with the monomeric functional protein. This activity is translated into an unprecedented anti-aggregation potency and the ability to abrogate the oligomers toxicity. With a structure-function relationship in hand, we identified a human peptide expressed in the brain and in the gastrointestinal tract with exceptional binding, antiaggregation, and detoxifying properties, which suggests it might play a protective role against synucleinopathies. The chemical entities we describe here represent a new therapeutic paradigm and are promising tools to assist diagnosis by selectively detecting -synuclein pathogenic species in biofluids.

biophysics↗

bioRxiv2020

The extent of protein hydration dictates the preference for heterogeneous or homogeneous nucleation generating either parallel or antiparallel β-sheet α-synuclein aggregates

-Synuclein amyloid self-assembly is the hallmark of a number of neurodegenerative disorders, including Parkinsons disease, although there is still very limited understanding about the factors and mechanisms that trigger this process. Primary nucleation has been observed to be initiated in vitro at hydrophobic/hydrophilic interfaces by heterogeneous nucleation generating parallel {beta}-sheet aggregates, although no such interfaces have yet been identified in vivo. In this work, we have discovered that -synuclein can self-assemble into amyloid aggregates by homogeneous nucleation, without the need of an active surface, and with a preference for an antiparallel {beta}-sheet arrangement. This particular structure has been previously proposed to be distinctive of stable toxic oligomers and we here demonstrate that it indeed represents the most stable structure of the preferred amyloid pathway triggered by homogeneous nucleation under limited hydration conditions, including those encountered inside -synuclein droplets generated by liquid-liquid phase separation. In addition, our results highlight the key role that water plays not only in modulating the transition free energy of amyloid nucleation, and thus governing the initiation of the process, but also in dictating the type of preferred primary nucleation and the type of amyloid polymorph generated depending on the extent of protein hydration. These findings are particularly relevant in the context of in vivo -synuclein aggregation where the protein can encounter a variety of hydration conditions in different cellular microenvironments, including the vicinity of lipid membranes or the interior of membraneless compartments, which could lead to the formation of remarkably different amyloid polymorphs by either heterogeneous or homogeneous nucleation.

biophysics↗