A5010742072- Autophagy in Disease and Therapy
- interferon and immune responses
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- DNA Repair Mechanisms
- Bacterial Genetics and Biotechnology
- NF-κB Signaling Pathways
- Signaling Pathways in Disease
- vaccines and immunoinformatics approaches
- Ubiquitin and proteasome pathways
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Lysosomal Storage Disorders Research
- RNA modifications and cancer
- Calcium signaling and nucleotide metabolism
- Immunotherapy and Immune Responses
- Protein Tyrosine Phosphatases
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
The University of Melbourne
2020-2025
Walter and Eliza Hall Institute of Medical Research
2020-2025
MRC Laboratory of Molecular Biology
2024
University of Wollongong
2018-2019
Abstract Limited experimental tools are available to study the consequences of collisions between DNA-bound molecular machines. Here, we repurpose a catalytically inactivated Cas9 (dCas9) construct as generic, novel, targetable protein–DNA roadblock for studying mechanisms underlying enzymatic activities on DNA substrates in vitro . We illustrate broad utility this tool by demonstrating replication fork arrest specifically bound dCas9–guideRNA complex viral, bacterial and eukaryotic forks
The ubiquitin kinase PINK1 accumulates on damaged mitochondria to trigger mitophagy, and loss-of-function mutations cause early onset Parkinson’s disease. Nucleotide analogs such as kinetin triphosphate (KTP) were reported enhance activity may represent a therapeutic strategy for the treatment of Here, we investigate interaction with nucleotides, including KTP. We establish cryo-EM platform exploiting dodecamer assembly Pediculus humanus corporis ( Ph ) determine structures bound AMP-PNP...
Mutations in the ubiquitin kinase PINK1 cause early onset Parkinson’s Disease, but how is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We determined a 3.1-Å resolution cryo-electron microscopy structure of dimeric human an endogenous array TOM and VDAC complexes. Symmetric arrangement two core around central VDAC2 dimer facilitated by TOM5 TOM20, both which also bind C-lobes. enters mitochondria through proximal TOM40 barrel complex, guided...
Substantial evidence indicates that a decline in mitochondrial health contributes to the development of Parkinson disease. Accordingly, therapeutic stimulation mitophagy, autophagic turnover dysfunctional mitochondria, is promising approach treat An attractive target such setting PINK1, protein kinase initiates mitophagy cascade. Previous reports suggest PINK1 activity can be enhanced by kinetin triphosphate (KTP), an enlarged ATP analog acts as alternate phosphate donor for during...
Abstract Coronaviruses, including SARS-CoV-2, encode multifunctional proteases that are essential for viral replication and evasion of host innate immune mechanisms. The papain-like protease PLpro cleaves the polyprotein, reverses inflammatory ubiquitin anti-viral ubiquitin-like ISG15 protein modifications 1,2 . Drugs target SARS-CoV-2 (hereafter, SARS2 PLpro) may hence be effective as treatments or prophylaxis COVID-19, reducing load reinstating responses 3 We here characterise in molecular...
DNA replication occurs on chromosomal while processes such as repair, recombination and transcription continue. However, we have limited experimental tools to study the consequences of collisions between DNA-bound molecular machines. Here, repurpose a catalytically inactivated Cas9 (dCas9) construct fused photo-stable dL5 protein fluoromodule novel, targetable protein-DNA roadblock for studying fork arrest at single-molecule level in vitro well vivo . We find that specifically bound...
Abstract PINK1 is a ubiquitin kinase that accumulates on damaged mitochondria to trigger mitophagy, and loss-of-function mutations cause early onset Parkinson’s disease. Nucleotide analogues such as kinetin triphosphate (KTP) have been suggested enhance activity may represent therapeutic strategy for the treatment of Here, we investigate interaction with nucleotides, including KTP. We establish cryo-EM platform exploiting previously observed dodecamer assembly Pediculus humanus corporis ( Ph...