Biology subjects

Blighe, K.

Publications and source records attributed to Blighe, K..

4 recordsLinked to original sources

bioRxiv2024

An integrated stress response-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation

The Integrated Stress Response (ISR) is a corrective physiological program to restore cellular homeostasis that is based on the attenuation of global protein synthesis and a resource-enhancing transcriptional programme. GCN2 is the oldest of four kinases that are activated by diverse cellular stresses to trigger the ISR and acts as the primary responder to amino acid shortage and ribosome collisions. Here, using a broad multi-omic approach, we uncover an ISR-independent role of GCN2. GCN2 inhibition or depletion in the absence of discernible stress causes excessive protein synthesis and ribosome biogenesis, perturbs the cellular translatome, and results in a dynamic and broad loss of metabolic homeostasis. Cancer cells that rely on GCN2 to keep protein synthesis in check under conditions of full nutrient availability depend on GCN2 for survival and unrestricted tumour growth. Our observations define an ISR-independent role of GCN2 in regulating the cellular proteome and translatome and suggest new avenues for cancer therapies based on unleashing excessive mRNA translation.

cancer biology↗

bioRxiv2020

ImmunoCluster: A computational framework for the non-specialist to immune profile cellular heterogeneity using liquid and imaging mass, and flow cytometry datasets

High dimensional cytometry is an innovative tool for immune monitoring in health and disease, it has provided novel insight into the underlying biology as well as biomarkers for a variety of diseases. However, the analysis of multiparametric "big data" usually requires specialist computational knowledge. Here we describe ImmunoCluster (https://github.com/kordastilab/ImmunoCluster) an R package for immune profiling cellular heterogeneity in high dimensional liquid and imaging mass cytometry, and flow cytometry data, designed to facilitate computational analysis by a non-specialist. The analysis framework implemented within ImmunoCluster is readily scalable to millions of cells and provides a variety of visualization and analytical approaches, as well as a rich array of plotting tools that can be tailored to users needs. The protocol consists of three core computational stages: 1, data import and quality control, 2, dimensionality reduction and unsupervised clustering; and 3, annotation and differential testing, all contained within an R-based open-source framework.

systems biology↗

bioRxiv2020

Identification of genetic factors controlling phosphorus utilization efficiency in wheat by genome-wide association study with principal component analysis

Despite the economic importance of P utilization efficiency, information on genetic factors underlying this trait remains elusive. To address that, we performed a genome-wide association study in a spring wheat diversity panel ranging from landraces to elite varieties. We evaluated the phenotype variation for P utilization efficiency in controlled conditions and genotype variation using wheat 90K SNP array. Phenotype variables were transformed into a smaller set of uncorrelated principal components that captured the most important variation data. We identified two significant loci associated with both P utilization efficiency and the 1st principal component on chromosomes 3A and 4A: qPE1-3A and qPE2-4A. Annotation of genes at these loci revealed 53 wheat genes, among which 6 were identified in significantly enriched pathways. The expression pattern of these 6 genes indicated that TraesCS4A02G481800, involved in pyruvate metabolism and TCA cycle, had a significantly higher expression in the P efficient variety under limited P conditions. Further characterization of these loci and candidate genes can help stimulate P utilization efficiency in wheat. KEY MESSAGEWe report two new loci for P utilization efficiency on chromosomes 3A and 4A of wheat. The prioritized candidate genes at these loci can be investigated by molecular biology techniques to improve P efficiency in wheat and grass relatives.

genomics↗

bioRxiv2018

New insights in Tibial muscular dystrophy revealed by protein-protein interaction networks

1. Introduction 1. Introduction 2. Materials and Methods 3. Results and discussion 4. Conclusion Conflict of interest Reference Tibial muscular dystrophy (TMD; OMIM: #600334) or Udd myopathy is an autosomal dominant distal myopathy that shows a high prevalence in the Finnish population (Udd et al., 1991; Udd et al., 1993; Udd et al., 2005; Pollazzon et al., 2010), however, other cases in European countries have been reported as in France (de Seze et al., 1998), Belgium (Van den Bergh et al., 2003), Italy (Pollazzon et al., 2010), and Spain (Hackman et al., 2008).\n\nTMD is caused by mutations (11-bp insertion-deletion) in the final exon, exon 364, in the TTN ...

bioinformatics↗