A5009290085- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- interferon and immune responses
- Amyotrophic Lateral Sclerosis Research
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Parkinson's Disease Mechanisms and Treatments
- Hereditary Neurological Disorders
- Nerve injury and regeneration
University of Sheffield
2022-2024
Spinal muscular atrophy, the leading genetic cause of infant mortality, is a motor neuron disease caused by low levels survival (SMN) protein. SMN multifunctional protein that implicated in numerous cytoplasmic and nuclear processes. Recently, increasing attention being paid to role maintenance DNA integrity. damage genome instability have been linked range neurodegenerative diseases. The ribosomal (rDNA) represents particularly unstable locus undergoing frequent breakage. Instability rDNA...
Dipeptide repeat (DPR) proteins are aggregation-prone polypeptides encoded by the pathogenic GGGGCC expansion in C9ORF72 gene, most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. In this study, we focus on role poly-GA DPRs disease spread. We demonstrate that recombinant oligomers can directly convert into solid-like aggregates form characteristic β-sheet fibrils vitro. To dissect process cell-to-cell DPR transmission, closely follow fate either their...
New therapeutic targets are a valuable resource for treatment of SARS-CoV-2 viral infection. Genome-wide association studies have identified risk loci associated with COVID-19, but many comorbidities and not specific to host–virus interactions. Here, we identify experimentally validate link between reduced expression EXOSC2 replication. was one the 332 host proteins examined, all which interact directly proteins. Aggregating COVID-19 genome-wide statistics gene-specific eQTLs revealed an...
Abstract Mutations within GLT8D1 contribute to familial amyotrophic lateral sclerosis. Pathogenic mutations impair glycosyltransferase enzymatic function via a dominant negative mechanism, yet the downstream mechanism leading neurotoxicity is unclear. Here we show that p.R92C mutation causes fragmentation of Golgi network and reduces ganglioside expression membrane lipid rafts (MLRs), impaired neurotrophin signalling. Expression p.R92C-GLT8D1 in HEK293 cells mouse primary neurons GM1...
Spastic paraplegia 47 (SPG47) is a neurological disorder caused by mutations in the adaptor protein complex 4 β1 subunit (AP4B1) gene leading to AP-4 deficiency. SPG47 characterised progressive spastic paraplegia, global developmental delay, intellectual disability and epilepsy. Gene therapy aimed at restoring functional AP4B1 levels rational therapeutic strategy ameliorate disease phenotype. Here we report that single delivery of adeno-associated virus serotype 9 expressing hAP4B1...
Abstract New therapeutic targets are a valuable resource in the struggle to reduce morbidity and mortality associated with COVID-19 pandemic, caused by SARS-CoV-2 virus. Genome-wide association studies (GWAS) have identified risk loci, but some loci co-morbidities not specific host-virus interactions. Here, we identify experimentally validate link between reduced expression of EXOSC2 replication. was one 332 host proteins examined, all which interact directly proteins; interacts Nsp8 forms...