Biology subjects

Parkes, E.

Publications and source records attributed to Parkes, E..

4 recordsLinked to original sources

bioRxiv2024

IGFs regulate cancer cell immune evasion in prostate cancer

Insulin-like growth factor-1 (IGF-1) promotes prostate cancer (PCa) development and lethality, with immunosuppressive properties in other disease models. These studies investigated the tumor-intrinsic immune effects of IGF-1 in PCa to understand mechanisms underlying its poor immunotherapy response. Transcriptional profiling of human (DU145, 22Rv1) and murine (Myc-CaP) PCa cells revealed, through pathway enrichment, that cytokine signalling, antigen processing and presentation, and other immune regulatory pathways, were most suppressed by IGF-1. We went on to investigate changes in the expression of components of two key pathways responsible for cancer cell recognition by immune cells and immune evasion: antigen processing and presentation, and PD-L1 checkpoint expression. These pathways are crucial for determining immunotherapy response. IGF-1 downregulated transporters associated with antigen processing (TAPs), endoplasmic reticulum aminopeptidase-1 (ERAP-1), and Class I component {beta}2-microglobulin, without major changes in Class I allele expression. These effects were associated with reduced presentation of Class I complexes on the Myc-CaP cell surface suggesting altered peptide transport, processing, and/or presentation. In contrast, IGF-1 upregulated immune checkpoint CD274 (PD-L1) via IGF receptor/AKT/ERK-dependent signaling. Analysis of public data (TCGA Firehose Legacy PCa) revealed increased CD274 expression in PCa with high endogenous IGF1 and IGFBP5, markers of high IGF axis activity. Additionally, in primary PCa (n=32), multiplex immunofluorescence revealed higher PD-L1 expression in the central tumor of men with high serum IGF-1 promoting cancer cell immune evasion in PCa. These findings indicate a novel mechanism by which IGF-1 mediates immunosuppressive effects in malignant prostate epithelium, potentially explaining the poor responsiveness of PCa to immunotherapy and highlighting the complex interplay between IGF signaling and immune evasion.

cancer biology↗

bioRxiv2024

Magnetic Activation of Spherical Nucleic Acids for the Remote Control of Synthetic Cells

The advancement of synthetic cells as drug delivery devices hinges on the development of targeting strategies, in particular the controlled synthesis of biomolecules in-situ using a deeply penetrative stimulus. To address this, we have designed spherical nucleic acids comprising DNA promoter sequences decorating magnetic nanoparticle cores. By harnessing the heat dissipated from magnetic hyperthermia (a clinically-approved anticancer therapy) we tightly controlled cell-free protein synthesis. We then deployed a tissue phantom that is impenetrable by current activation methods to demonstrate the potential of this technology for the remote control of synthetic cells using deeply tissue-penetrating magnetic fields. This paves the way for targeting and controlling the in-situ synthesis of biomolecules deep within the body. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/608917v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@3cf352org.highwire.dtl.DTLVardef@18a8da3org.highwire.dtl.DTLVardef@159018aorg.highwire.dtl.DTLVardef@744529_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2024

Gene expression responses to environmental cues shed light on components of the migratory syndrome in butterflies

Migration is a complex behavior involving the synchronisation of many physiological and behavioral processes. Environmental cues must thus be interpreted to make decisions regarding resource allocation between, for example, migration or reproduction. In butterflies, the lack of host plants to sustain a new generation may indicate the need to migrate. Here, we used the painted lady butterfly (Vanessa cardui) as a model to characterize gene expression variation in response to host plant availability. Assessment of the response to host plant availability in adult female butterflies revealed significant modifications in gene expression, particularly within hormonal pathways (ecdysone oxidase and juvenile hormone esterase). We therefore hypothesize that tuning the ecdysone pathway may play a crucial role in regulating the timing of migration and reproduction in adult female painted lady butterflies. In addition, our analysis revealed significant enrichment of genes associated with lipid, carbohydrate, and vitamin biosynthesis, as well as the immune response. As environmental acquisition occurs throughout the life cycle, we also tracked gene expression responses to two other environmental cues across major developmental stages. Differences in both larval crowding and host plant availability during development resulted in significant changes in the expression of genes involved in development, reproduction and metabolism, particularly at the instar V larval stage. In summary, our results offer novel insights into how environmental cues affect expression profiles in migratory insects and highlight candidate genes that may underpin the migratory syndrome in the painted lady butterfly.

evolutionary biology↗

bioRxiv2020

Genome-wide association analysis reveals new insights into the genetic architecture of defensive, agro-morphological and quality-related traits in cassava

Cassava (Manihot esculenta) is one of the most important starchy root crops in the tropics due to its adaptation to marginal environments. Genetic progress in this clonally propagated crop can be accelerated through the discovery of markers and candidate genes that could be used in cassava breeding programs. We carried out a genome-wide association study (GWAS) using a panel of 5,310 clones developed at the International Institute of Tropical Agriculture - Nigeria. The population was genotyped at more than 100,000 SNP markers via genotyping-by-sequencing (GBS). Genomic regions underlying genetic variation for 14 traits classified broadly into four categories: biotic stress (cassava mosaic disease and cassava green mite severity); quality (dry matter content and carotenoid content) and plant agronomy (harvest index and plant type). We also included several agro-morphological traits related to leaves, stems and roots with high heritability. In total, 41 significant associations were uncovered. While some of the identified loci matched with those previously reported, we present additional association signals for the traits. We provide a catalogue of favourable alleles at the most significant SNP for each trait-locus combination and candidate genes occurring within the GWAS hits. These resources provide a foundation for the development of markers that could be used in cassava breeding programs and candidate genes for functional validation.

genetics↗