A5030809764- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Genetics and Neurodevelopmental Disorders
- Chemical Synthesis and Analysis
- Cellular transport and secretion
- Protein Structure and Dynamics
- Genomics and Rare Diseases
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Fungal and yeast genetics research
- Mass Spectrometry Techniques and Applications
- Algal biology and biofuel production
- Electrochemical sensors and biosensors
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- Erythrocyte Function and Pathophysiology
- Microbial Metabolic Engineering and Bioproduction
- Apelin-related biomedical research
Monash University
2022-2025
Australian Research Council
2024
Indiana University Bloomington
2021-2023
Florey Institute of Neuroscience and Mental Health
2018-2022
The University of Melbourne
2017-2022
ZHAW Zurich University of Applied Sciences
2011-2015
University of Zurich
2014
Baker, Gordon et al. present the first international case series describing neurodevelopmental disorder associated with Synaptotagmin 1 (SYT1) de novo missense mutations. Key features include movement abnormalities, severe intellectual disability, and hallmark EEG alterations. Expression of patients’ SYT1 mutations in mouse neurons disturbs presynaptic vesicle dynamics a mutation-specific manner.
Nuclear magnetic resonance (NMR) studies have revealed that fast methyl sidechain dynamics can report on entropically-driven allostery. Yet, NMR applications been largely limited to the super-microsecond motional regimes of G protein-coupled receptors (GPCRs). We use 13Cε-methionine chemical shift-based global order parameters test if ligands affect a thermostabilized GPCR, neurotensin receptor 1 (NTS1). establish NTS1 solution ensemble includes substates with lifetimes several, discrete...
The class A orphan G protein-coupled receptor (GPCR), GPR3, has been implicated in a variety of conditions, including Alzheimer's and premature ovarian failure. GPR3 constitutively couples with Gαs, resulting the production cAMP cells. While tool compounds several putative endogenous ligands have emerged for receptor, its ligand, if it exists, remains mystery. As novel potential drug targets, structures GPCRs increasing interest, revealing distinct modes activation, autoactivation, presence...
Synaptotagmin-1 (SYT1) is a critical mediator of neurotransmitter release in the central nervous system. Previously reported missense SYT1 variants C2B domain are associated with severe intellectual disability, movement disorders, behavioral disturbances, and electroencephalogram abnormalities. In this study, we expand genotypes phenotypes identify discriminating features disorder.
Using a discrete, intracellular 19F nuclear magnetic resonance (NMR) probe on transmembrane helix 6 of the neurotensin receptor 1 (NTS1), we aim to understand how ligands and transducers modulate receptor's structural ensemble in solution. For apo NTS1, NMR spectra reveal an at least three conformational substates (one inactive two active-like) equilibrium that exchange millisecond second timescale. Dynamic experiments these follow linear three-site process is both thermodynamically...
Abstract The neurotensin receptor 1 (NTS ) is a G protein-coupled (GPCR) with promise as drug target for the treatment of pain, schizophrenia, obesity, addiction, and various cancers. A detailed picture NTS structural landscape has been established by X-ray crystallography cryo-EM yet, molecular determinants why couples to protein versus arrestin transducers remain poorly defined. We used 13 C ε H 3 -methionine NMR spectroscopy show that binding phosphatidylinositol-4,5-bisphosphate (PIP2)...
Cell–cell communication via endogenous peptides and their receptors is vital for controlling all aspects of human physiology most signal through G protein-coupled (GPCRs). Disordered bind GPCRs complex modes which there are few representative crystal structures. The disordered peptide neurotensin (NT) a neuromodulator classical neurotransmitters such as dopamine glutamate, activation receptor 1 (NTS1). While several experimental structures show how NT binds NTS1, details about the structural...
Abstract G-protein coupled receptors are the largest family of integral membrane proteins found within human genome. They function as and modulators to a wide range ligands responses which crucial for health. GPCR study, specifically investigation structure interaction cognate ligands, is high priority. Limitations structural study can be traced in part, obtaining suitable quantities recombinant protein. We sought address limitations traditional technologies by utilising an Escherichia coli...
Summary Unlike many signaling proteins that function as binary switches between ‘on and off’ states, G protein-coupled receptors (GPCRs) exhibit basal activity can be increased or decreased by numerous ligands. A given receptor recognize multiple ligands, allosteric modulators, transducers to create a complex free energy landscape. Many of the lowest states have been captured static structural techniques while detailing wells’ widths, metastable transition them, is still in its infancy....
Abstract Purpose Synaptotagmin-1 (SYT1) is a critical mediator of neurotransmitter release in the central nervous system. Previously reported missense SYT1 variants C2B domain are associated with severe intellectual disability, movement disorders, behavioural disturbance and EEG abnormalities. Here, we expand genotypes phenotypes identify discriminating features this disorder. Methods We describe 22 individuals 15 de novo variants. Evidence for pathogenicity discussed, including ACMG...
ABSTRACT The neurotensin receptor 1 (NTS ) is a G protein-coupled (GPCR) with promise as drug target for the treatment of pain, schizophrenia, obesity, addiction, and various cancers. A detailed picture NTS structural landscape has been established by X-ray crystallography cryo-EM yet, molecular determinants why couples to protein versus arrestin transducers remain poorly defined. We used 13 C ε H 3 -methionine NMR spectroscopy show that phosphatidylinositol-4,5-bisphosphate (PIP2) promotes...
ABSTRACT Using a discrete, intracellular 19 F-NMR probe on transmembrane helix 6 (TM6) of the Neurotensin receptor 1 (NTS1), we aim to understand how ligands and transducers modulate receptor’s structural ensemble in solution. For apo NTS1, spectra reveal an at least three conformational substates (one inactive two active-like) equilibrium that exchange ms-s timescale. Dynamic NMR experiments these follow linear three-site process is both thermodynamically kinetically remodeled by...