A5069278376- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- RNA modifications and cancer
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Obsessive-Compulsive Spectrum Disorders
- Autism Spectrum Disorder Research
- Viral Infectious Diseases and Gene Expression in Insects
- Lipid Membrane Structure and Behavior
- Genetics, Aging, and Longevity in Model Organisms
- Genetics and Neurodevelopmental Disorders
- Cardiomyopathy and Myosin Studies
- Food Allergy and Anaphylaxis Research
- biodegradable polymer synthesis and properties
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Cellular transport and secretion
- Health, Environment, Cognitive Aging
- Renin-Angiotensin System Studies
- Genetic Associations and Epidemiology
University of Malta
2015-2025
Instituto de Neurologia Y Neurocirugia
2021
University of Turin
2021
University of Oxford
2006-2010
Genomics (United Kingdom)
2010
Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes...
Aggregation of the amyloid-forming α-synuclein (αS) protein is closely associated with etiology Parkinson's disease (PD), most common motor neurodegenerative disorder. Many studies have shown that soluble aggregation intermediates αS, termed oligomers, permeabilize a variety phospholipid membranes; thus, membrane disruption may represent key pathogenic mechanism αS toxicity. Given centrality mitochondrial dysfunction in PD, we therefore probed formation ion-permeable pores by oligomers...
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling neuronal survival, overexpression of ameliorates ALS phenotypes in vivo. Genome-wide association studies localize a large proportion risk variants within the non-coding genome, but further characterization has been limited by lack appropriate tools. By designing applying pipeline to identify pathogenic genetic variation enhancer...
The survival motor neuron (SMN) protein, the determining factor for spinal muscular atrophy (SMA), is complexed with a group of proteins in human cells. Gemin3 only RNA helicase SMN complex. Here, we report identification Drosophila melanogaster and investigate its function vivo. Like vertebrates, physically interacts Drosophila. Loss gemin3 results lethality at larval and/or prepupal stages. Before they die, mutant larvae exhibit declined mobility expanded neuromuscular junctions....
Membership of the survival motor neuron (SMN) complex extends to nine factors, including SMN protein, product spinal muscular atrophy (SMA) disease gene, Gemins 2–8 and Unrip. The best-characterised function this macromolecular machine is assembly Sm-class uridine-rich small nuclear ribonucleoprotein (snRNP) particles each member has a key role during process. So far, however, only little known about individual Gemin components in vivo. Here, we make use Drosophila model organism uncover...
Abstract Genetic isolates are compelling tools for mapping genes of inherited disorders. The archipelago Malta, a sovereign microstate in the south Europe is home to geographically and culturally isolated population. Here, we investigate epidemiology genetic profile Maltese patients with amyotrophic lateral sclerosis (ALS), identified throughout 2-year window. Cases were largely male (66.7%) predominant spinal onset symptoms (70.8%). Disease occurred around mid-age (median age: 64 years,...
Loss-of-function mutations in the KCNA1(Kv1.1) gene cause episodic ataxia type 1 (EA1), a neurological disease characterized by cerebellar dysfunction, ataxic attacks, persistent myokymia with painful cramps skeletal muscles, and epilepsy. Precision medicine for EA1 treatment is currently unfeasible, as no drug that can enhance activity of Kv1.1-containing channels offset functional defects caused KCNA1 has been clinically approved. Here, we uncovered niflumic acid (NFA), prescribed...
The SMN-Gemins complex is composed of Gemins 2–8, Unrip and the survival motor neuron (SMN) protein. Limiting levels SMN result in neuromuscular disorder, spinal muscular atrophy (SMA), which presently untreatable. most-documented function concerns assembly spliceosomal small nuclear ribonucleoproteins (snRNPs). Despite multiple genetic studies, Gemin proteins have not been identified as prominent modifiers SMN-associated mutant phenotypes. In present report, we make use Drosophila model...
Abstract The predominant motor neuron disease in infants and adults is spinal muscular atrophy (SMA) amyotrophic lateral sclerosis (ALS), respectively. SMA caused by insufficient levels of the Survival Motor Neuron (SMN) protein, which operates as part multiprotein SMN complex that includes DEAD-box RNA helicase Gemin3/DDX20/DP103. C9orf72 , SOD1 TDP-43 FUS are ranked four major genes causing familial ALS. Accumulating evidence has revealed a surprising molecular overlap between Here, we ask...
Gems or 'Gemini of Cajal bodies' are spherical nuclear aggregates SMN (survival motor neurons) complexes that frequently overlap bodies. Although described and characterized in mammalian tissues, gems have not been reported invertebrates. Stimulation gem formation the fruitfly Drosophila melanogaster was investigated through constitutive overexpression a fluorescently tagged transgene DEAD-box complex member, Gemin3, wild-type tissues. expression predominantly cytoplasmic larval brain cells,...