A5005890933- Cellular transport and secretion
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Nuclear Structure and Function
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- 14-3-3 protein interactions
- DNA Repair Mechanisms
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Lysosomal Storage Disorders Research
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
MRC Protein Phosphorylation and Ubiquitylation Unit
2024
University of Dundee
2024
University of Oxford
2020-2022
Nanyang Technological University
2019
Walter and Eliza Hall Institute of Medical Research
2013-2018
The University of Melbourne
2013-2018
Cholesterol is a major structural component of the plasma membrane (PM). The majority PM cholesterol forms complexes with other lipids, making it inaccessible for intracellular transport. Transition between accessible and pools maintains cellular homeostasis, but how cells monitor accessibility remains unclear. We show that endoplasmic reticulum (ER)-anchored lipid transfer proteins, GRAMD1s, sense transport to ER. GRAMD1s bind one another populate ER-PM contacts by sensing transient...
Abstract Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding branched function cell signaling has been stunted by the absence accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins devise approaches to probe K48–K63-branched function. We establish method monitor cleavage linkages within complex unveil ATXN3 MINDY as debranching enzymes. engineer K48–K63 branch-specific...
Misfolded proteins in the endoplasmic reticulum (ER) are degraded by ER-associated degradation (ERAD). Although ERAD components involved of luminal substrates well characterized, much less is known about quality control membrane proteins. Here, we analyzed pathways two short-lived ER model mammalian cells. Using a CRISPR-Cas9 genome-wide library screen, identified an branch required for subset biochemical and mass spectrometry approaches, showed that this defined complex consisting ubiquitin...
Nuclear architecture and functions depend on dynamic interactions between nuclear components (such as chromatin) inner membrane (INM) proteins. Mutations in INM proteins interfering with these result disease. However, mechanisms controlling the levels turnover of remain unknown. Here, we describe a mechanism regulated degradation SUN domain-containing protein 2 (SUN2). We show that Casein Kinase C-terminal domain Envelope Phosphatase 1 (CTDNEP1) have opposing effects SUN2 by regulating...
Significance The T-cell antigen receptor (TCR) is an eight-subunit modular biosensor that detects the presence of pathogen-derived molecular fragments in infected cells and tissues. No atomic-resolution structure has been determined for intact complex, mechanism by which it transmits signals across cell membrane remains poorly defined. Using a combination biochemical, biophysical, computational approaches to study assembled complex cellular membranes, we identified evolutionarily conserved...
Physical interactions among the lipid-embedded alpha-helical domains of membrane proteins play a crucial role in folding and assembly protein complexes dynamic processes such as transmembrane (TM) signaling regulation cell-surface levels. Understanding structural features driving association particular sequences requires sophisticated biophysical biochemical analyses TM peptide complexes. However, extreme hydrophobicity makes them very difficult to manipulate using standard chemistry...
Abstract Nuclear architecture and functions depend on dynamic interactions between nuclear components (such as chromatin) inner membrane (INM) proteins. Mutations in INM proteins interfering with these result disease. However, mechanisms controlling the levels turnover of remain unknown. Here, we describe a mechanism regulated degradation SUN domain-containing protein 2 (SUN2). We show that Casein Kinase II C-terminal domain Envelope Phosphatase 1 (CTDNEP1) have opposing effects SUN2 by...