A5031170324- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bioinformatics and Genomic Networks
- Molecular Biology Techniques and Applications
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Cancer-related gene regulation
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Circular RNAs in diseases
- Advanced Proteomics Techniques and Applications
- Genomics and Phylogenetic Studies
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Chromosomal and Genetic Variations
- Single-cell and spatial transcriptomics
- Fungal and yeast genetics research
- Microbial Metabolic Engineering and Bioproduction
- Machine Learning in Bioinformatics
- DNA and Nucleic Acid Chemistry
- Genomics and Rare Diseases
Garvan Institute of Medical Research
2018-2025
UNSW Sydney
2019-2024
EMBL Australia
2018-2024
University of Toronto
2012-2023
St Vincent's Clinic
2019-2022
MRC Laboratory of Molecular Biology
2013-2018
Health First
2017
Donnelly College
2016
Medical Research Council
2014
European Molecular Biology Laboratory
2011-2013
Traditionally, protein-protein interactions were thought to be mediated by large, structured domains. However, it has become clear that the interactome comprises a wide range of binding interfaces with varying degrees flexibility, ranging from rigid globular domains disordered regions natively lack structure. Enrichment for disorder in highly connected hub proteins and its correlation organism complexity hint at functional importance regions. Nevertheless, they have not yet been extensively...
Linear motifs are short, evolutionarily plastic components of regulatory proteins and provide low-affinity interaction interfaces. These compact modules play central roles in mediating every aspect the functionality cell. They particularly prominent cell signaling, controlling protein turnover directing localization. Given their importance, our understanding is surprisingly limited, largely as a result difficulty discovery, both experimentally computationally. The Eukaryotic Motif (ELM)...
The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short motifs (SLiMs). For >10 years, this has provided the scientific community with freely accessible guide to biology function of motifs. current version ELM contains ∼200 different classes over 2400 experimentally validated instances manually curated from >2000 publications. Furthermore, detailed motif-mediated interactions been annotated made available in...
A resource centered on short linear motifs provides a repository and exploratory tool for conditional protein interactions.
Abstract An average shotgun proteomics experiment detects approximately 10,000 human proteins from a single sample. However, individual are typically identified by peptide sequences representing small fraction of their total amino acids. Hence, an fails to distinguish different protein variants and isoforms. Deeper proteome sequencing is therefore required for the global discovery Using six cell lines, proteases, deep fractionation three tandem mass spectrometry fragmentation methods, we...
Linear motifs are short segments of multidomain proteins that provide regulatory functions independently protein tertiary structure. Much intracellular signalling passes through modifications at linear motifs. Many thousands motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, difficult to predict de novo in sequences due the difficulty obtaining robust statistical assessments. The ELM resource http://elm.eu.org/ provides an expanding...
Progression through the mitotic cell cycle requires periodic regulation of gene function at levels transcription, translation, protein-protein interactions, post-translational modification and degradation. However, role alternative splicing (AS) in temporal control is not well understood. By sequencing human transcriptome two continuous cycles, we identify ~1300 genes with cycle-dependent AS changes. These are significantly enriched functions linked to control, yet they do overlap subject...
Significance In higher organisms, most genes consist of several disconnected regions (exons), which are combined in various ways to produce different gene transcripts from the same gene. Such alternative exon usage is thought contribute ability organisms generate cell types and tissues a single genome. However, recent evidence has also suggested that much might be noise with no particular function. We reconcile these two views by comparing how exons used for patterns across change or stay...
Mutations in short linear motifs impair the functions of intrinsically disordered proteins cellular signaling/regulation and contribute substantially to human diseases.
Gene fusions are common cancer-causing mutations, but the molecular principles by which fusion protein products affect interaction networks and cause disease not well understood. Here, we perform an integrative analysis of structural, interactomic, regulatory properties thousands putative proteins. We demonstrate that genes form (i.e., parent genes) tend to be highly connected hub genes, whose enriched in structured disordered interaction-mediating features. Fusion often results loss these...
Regulation of translation during human development is poorly understood, and its dysregulation associated with Rett syndrome (RTT). To discover shifts in mRNA ribosomal engagement (RE) neurodevelopment, we use parallel translating ribosome affinity purification sequencing (TRAP-seq) RNA (RNA-seq) on control RTT induced pluripotent stem cells, neural progenitor cortical neurons. We find that 30% transcribed genes are translationally regulated, including key gene sets (neurodevelopment,...
Abstract Autism spectrum disorder (ASD) includes a set of highly heritable neurodevelopmental syndromes characterized by social and communication impairment, repetitive behaviour, intellectual disability. Although mutations in multiple genes have been associated to ASD, most patients lack detectable genetic alterations. For this reason, environmental factors are commonly thought also contribute ASD aetiology. Transcriptome analyses revealed that autistic brains possess distinct gene...