A5058343547- Genetics, Aging, and Longevity in Model Organisms
- Nerve injury and regeneration
- Circadian rhythm and melatonin
- Photoreceptor and optogenetics research
- 3D Printing in Biomedical Research
- Neurobiology and Insect Physiology Research
- Neuroscience and Neural Engineering
- Spaceflight effects on biology
- Amyotrophic Lateral Sclerosis Research
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Muscle Physiology and Disorders
- Neurogenetic and Muscular Disorders Research
- Axon Guidance and Neuronal Signaling
- Cellular Mechanics and Interactions
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Parkinson's Disease Mechanisms and Treatments
- Phagocytosis and Immune Regulation
- Signaling Pathways in Disease
- Olfactory and Sensory Function Studies
- SARS-CoV-2 and COVID-19 Research
- Neuroscience and Neuropharmacology Research
- Gene expression and cancer classification
- MicroRNA in disease regulation
Park Centre for Mental Health
2016-2025
The University of Queensland
2016-2025
Rockefeller University
2006-2007
Howard Hughes Medical Institute
2006
University of California, San Francisco
2006
Institute of Genetics and Biophysics
1994-2005
University of California, San Diego
2004
Cancer Genetics (United States)
1999
National Institutes of Health
1999
National Human Genome Research Institute
1999
Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect brain and are associated with neurological symptoms through poorly understood mechanisms. We show that SARS-CoV-2 infection induces fusion between neurons glia in mouse human organoids. reveal this is caused by viral fusogen, as it fully mimicked expression spike (S) protein or unrelated fusogen...
Phosphine is a small redox-active gas that used to protect global grain reserves, which are threatened by the emergence of phosphine resistance in pest insects. We find polymorphisms responsible for genetic cluster around catalytic disulfide or dimerization interface dihydrolipoamide dehydrogenase (DLD) insects (Rhyzopertha dominica and Tribolium castaneum) nematodes (Caenorhabditis elegans). DLD core metabolic enzyme representing new class factor toxin. It participates four key steps...
Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of output. In amyotrophic lateral sclerosis (ALS) LVPNs spinal degenerate. The pathogenesis neural degeneration is unknown in ALS; 10% cases have a genetic cause, whereas 90% are sporadic, with most latter showing TDP-43 inclusions. Clinical experimental evidence implicate excitotoxicity as prime aetiological candidate. Using patch clamp dye-filling techniques brain slices,...
Oxidative stress, caused by the accumulation of reactive oxygen species (ROS), is a pathological factor in several incurable neurodegenerative conditions as well stroke. However, our knowledge genetic elements that can be manipulated to protect neurons from oxidative stress-induced cell death still very limited. Here, using Caenorhabditis elegans model system, combined with optogenetic tool KillerRed spatially and temporally control ROS generation, we identify previously uncharacterized...
We have investigated the role of Caenorhabditis elegans RAD-51 during meiotic prophase and embryogenesis, making use silencing effect RNA interference (RNAi). rad-51 RNAi leads to severe defects in chromosome morphology diakinesis oocytes. explored mutants lacking fundamental components recombination machinery. If double-strand breaks are prevented by spo-11 mutation, does not affect appearance. This is consistent with a for downstream initiation recombination. In absence MRE-11, as SPO-11,...
Functional neuronal recovery following injury arises when severed axons reconnect with their targets. In Caenorhabditis elegans laser-induced axotomy, the axon still attached to cell body is able regrow and its separated distal fragment. Here we show that reconnection of fragments during regeneration C. mechanosensory neurons occurs through a mechanism axonal fusion, which prevents Wallerian degeneration Through electron microscopy analysis imaging photoconvertible fluorescent protein Kaede,...
Axonal degeneration arises as a consequence of neuronal injury and is common hallmark number neurodegenerative diseases. However, the genetic causes cellular mechanisms that trigger this process are still largely unknown. Based on forward screening in C. elegans, we have identified α-tubulin acetyltransferase gene mec-17 causing spontaneous, adult-onset, progressive axonal degeneration. Loss MEC-17 leads to microtubule instability, reduction mitochondrial number, disrupted transport, with...
Inactivation of selected neurons in vivo can define their contribution to specific developmental outcomes, circuit functions, and behaviors. Here, we show that the optogenetic tool KillerRed selectively, rapidly, permanently inactivates different classes C. elegans response a single light stimulus, through generation reactive oxygen species (ROS). Ablation scales from individual animals multiple populations be applied freely behaving animals. Using spatially restricted illumination,...
Transactive response DNA-binding protein-43 (TDP-43) is involved in gene regulation via the control of RNA transcription, splicing, and transport. TDP-43 a major protein component ubiquinated inclusions that are found amyotrophic lateral sclerosis (ALS); however, function at neuromuscular junction (NMJ) its role ALS pathogenesis largely unknown. Here, we show TDP-43Q331K mutation mice resulted impaired neurotransmission by age 3 mo, preceding deficits motor neuron loss, which were observed...
C. elegans is an excellent model system for studying neuroscience using genetics because of its relatively simple nervous system, sequenced genome, and the availability a large number transgenic mutant strains. Recently, microfluidic devices have been used high-throughput genetic screens, replacing traditional methods manually handling elegans. However, orientation nematodes within random often not conducive to inspection, hindering visual analysis overall throughput. In addition, while...
We present a high-density microfluidic device for target-selective illumination, selective stimulation, and long-term monitoring of<italic>C. elegans</italic>.
Significance Nervous system injury can cause lifelong disability, because repair rarely leads to reconnection with the target tissue. In nematode Caenorhabditis elegans and in several other species, regeneration proceed through a mechanism of axonal fusion, whereby regrowing axons reconnect fuse their own separated fragments, rapidly efficiently restoring original tract. We have found that process fusion restores full function damaged neurons. addition, we show injury-induced changes...
Kallmann syndrome is an inherited disorder defined by the association of anosmia and hypogonadism, owing to impaired targeting migration olfactory axons gonadotropin-releasing hormone secreting neurons. The gene responsible for X-linked form syndrome, KAL-1, encodes a secreted protein still elusive function. It has been proposed that KAL-1 might be involved in some aspects axon guidance. However, unavailability mouse model, difficulties studying cellular axonal vertebrates have hampered...
Microtubules have been known for decades to be basic elements of the cytoskeleton. They form long, dynamic, rope-like structures within cell that are essential mitosis, maintenance shape, and intracellular transport. More recently, in vitro studies implicated microtubules as signaling molecules that, through changes their stability, potential trigger growth axons dendrites developing neurons. In this study, we show specific mutations Caenorhabditis elegans mec-7/β-tubulin gene cause ectopic...