Biology subjects

McLean, P.

Publications and source records attributed to McLean, P..

4 recordsLinked to original sources

bioRxiv2025

Jack of all trades and master of most: Carpobrotus taxa show no trade-off in reproductive strategies

O_LIThe ability to reproduce via multiple strategies is crucial for the invasion success of alien plant species. Here, we use Carpobrotus taxa (species and hybrids) to explore how trade-offs between and within these strategies may influence plant invasion dynamics. Native to South Africa, Carpobrotus plants are globally prominent in coastal ecosystems, reproducing by seed and clonally, and frequently hybridizing in both native and introduced regions. Three genetically distinct clusters were previously identified, with evidence of hybridization within and between these clusters in native and non-native ranges. C_LIO_LIWe collected fruit samples from populations representing the genetic clusters and their hybrids across native and non-native ranges (i.e., Europe, California, and New Zealand). These genetic clusters reflect the complex taxonomy of Carpobrotus, where species boundaries are unclear due to hybridization and morphological similarity. We then assessed seed set, seed mass, germination rates, and early growth under varying abiotic conditions alongside genetic estimates of clonality. C_LIO_LIGermination rates were influenced by temperature, moisture, and nutrient levels. Non-native populations demonstrated higher seed set, seed mass, and germination success compared to native populations, indicating a stronger investment in sexual reproduction. These populations also showed higher levels of clonality, shown by lower genotypic richness, suggesting that both reproductive strategies enhance invasive potential. C_LIO_LIHigh-clonality populations produced more seeds, demonstrating that the two reproductive strategies are not mutually exclusive. These results highlight the importance of multiple reproductive strategies for the establishment and spread of Carpobrotus taxa and provide insights into the mechanisms driving their global success. C_LI

plant biology↗

bioRxiv2023

Conifers concentrate large numbers of NLR immune receptor genes on one chromosome

Nucleotide-binding domain and Leucine-rich Repeat (NLR) immune receptor genes form a major line of defence in plants, acting in both pathogen recognition and resistance machinery activation. NLRs are reported to form large gene clusters in limber pine (Pinus flexilis) but it is unknown how widespread this genomic architecture may be among the extant species of conifers (Pinophyta). We used comparative genomic analyses to assess patterns in the abundance, diversity and genomic distribution of NLR genes. Chromosome-level whole genome assemblies and high-density linkage maps in the Pinaceae, Cupressaceae, Taxaceae and other gymnosperms were scanned for NLR genes using existing and customised pipelines. Discovered genes were mapped across chromosomes and linkage groups, and analysed phylogenetically for evolutionary history. Conifer genomes are characterised by dense clusters of NLR genes, highly localised on one chromosome. These clusters are rich in TNL-encoding genes, which seem to have formed through multiple tandem duplication events. In contrast to angiosperms and non-coniferous gymnosperms, genomic clustering of NLR genes is ubiquitous in conifers. NLR-dense genomic regions are likely to influence a large part of the plants resistance, informing our understanding of adaptation to biotic stress and the development of genetic resources through breeding. Plain language summaryNLR immune receptor genes are important in pest, disease and drought resistance of plants. In the giga-genomes of conifers, they concentrate on very small chromosomal regions. These regions act as important reservoirs for NLR diversity and can be used in breeding to improve the resilience of conifer trees.

genomics↗

bioRxiv2018

Alpha-synuclein-induced mitochondrial dysfunction is mediated via a sirtuin 3-dependent pathway.

The sirtuins are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent enzymes that play a broad role in cellular metabolism and aging. Mitochondrial sirtuin 3 (SIRT3) is downregulated in aging and age-associated diseases such as cancer and neurodegeneration and plays a major role in maintaining mitochondrial function and preventing oxidative stress. Mitochondria dysfunction is central to the pathogenesis of Parkinson disease with mutations in mitochondrial-associated proteins such as PINK1 and parkin causing familial Parkinson disease. Here, we demonstrate that the presence of alpha-synuclein oligomers in mitochondria induce a corresponding decrease in mitochondrial SIRT3 activity and decreased mitochondrial biogenesis. We show that SIRT3 downregulation in the presence of alpha-synuclein accumulation is accompanied by increased phosphorylation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB), increased phosphorylation of dynamin-related protein 1(DRP1) and decreased levels of optic atrophy 1 (OPA1), which are indicative of impaired mitochondrial dynamics. Treatment with the AMPK agonist 5-aminoimidazole-4-carboxamide-1-{beta}-d-ribofuranoside (AICAR) restores SIRT3 expression and improves alpha-synuclein-induced mitochondrial dysfunction by decreasing oligomer formation. The accumulation of alpha-synuclein oligomers in mitochondria corresponds with SIRT3 downregulation not only in an experimental cellular model, but also in vivo in a rodent model of Parkinson's disease, and importantly in human post mortem brains with neuropathologically confirmed Lewy body disease (LBD). Taken together our findings suggest that pharmacologically increasing SIRT3 levels will counteract syn-induced mitochondrial dysfunction by normalizing mitochondrial bioenergetics. These data support a protective role for SIRT3 in Parkinson disease-associated pathways and reveals significant mechanistic insight into the interplay of SIRT3 and syn.

neuroscience↗

bioRxiv2018

A CRISPR/Cas9 based strategy to manipulate the Alzheimer’s amyloid pathway

The gradual accumulation of amyloid-{beta} (A{beta}) is a neuropathologic hallmark of Alzheimers disease (AD); playing a key role in disease progression. A{beta} is generated by the sequential cleavage of amyloid precursor protein (APP) by {beta}- and {gamma}-secretases, with BACE-1 ({beta}-site APP cleaving enzyme-1) cleavage as the rate limiting step 1-3. CRISPR/Cas9 guided gene-editing is emerging as a promising tool to edit pathogenic mutations and hinder disease progression 4,5,6 However, few studies have applied this technology to neurologic diseases 7-9. Besides technical caveats such as low editing efficiency in brains and limited in vivo validation 7, the canonical approach of mutation-correction would only be applicable to the small fraction of neurodegenerative cases that are inherited (i.e. < 10% of AD, Parkinsons, ALS); with a new strategy needed for every gene. Moreover, feasibility of CRISPR/Cas9 as a therapeutic possibility in sporadic AD has not been explored. Here we introduce a strategy to edit endogenous APP at the extreme C-terminus and reciprocally manipulate the amyloid pathway - attenuating {beta}-cleavage and A{beta}, while up-regulating neuroprotective a-cleavage. APP N-terminus, as well as compensatory APP homologues remain intact, and key physiologic parameters remain unaffected. Robust APP-editing is seen in cell lines, cultured neurons, human embryonic stem cells/iPSC-neurons, and mouse brains. Our strategy works by limiting the physical association of APP and BACE-1, and we also delineate the mechanism that abrogates APP/BACE-1 interaction in this setting. Our work offers an innovative cut and silence gene-editing strategy that could be a new therapeutic paradigm for AD.

neuroscience↗