A5059178501- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Polymer Surface Interaction Studies
- Cellular Mechanics and Interactions
- Epigenetics and DNA Methylation
- Electrospun Nanofibers in Biomedical Applications
- Sarcoma Diagnosis and Treatment
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Ubiquitin and proteasome pathways
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Bacterial Genetics and Biotechnology
- Tissue Engineering and Regenerative Medicine
- Erythrocyte Function and Pathophysiology
- Bacteriophages and microbial interactions
- RNA Research and Splicing
- Genetics, Aging, and Longevity in Model Organisms
- Ion channel regulation and function
- Advanced Polymer Synthesis and Characterization
- 14-3-3 protein interactions
- Private Equity and Venture Capital
- Advanced Fluorescence Microscopy Techniques
- Nuclear Structure and Function
EMBL Australia
2020-2023
UNSW Sydney
2016-2023
ARC Centre of Excellence in Advanced Molecular Imaging
2020-2021
Max Delbrück Center
2011-2020
Max Planck Institute of Molecular Cell Biology and Genetics
2008-2011
Max Planck Society
2010-2011
Humboldt-Universität zu Berlin
2010-2011
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2002-2004
University of Washington
2004
XMAP215/Dis1 family proteins positively regulate microtubule growth. Repeats at their N termini, called TOG domains, are important for this function. While domains directly bind tubulin dimers, it is unclear how interaction translates to polymerase activity. Understanding the functional roles of further complicated by fact that number these present in different species varies. Here, we take advantage a recent crystal structure third domain from Caenorhabditis elegans , Zyg9, and mutate key...
Plus-end-tracking proteins (+TIPs) are localized at the fast-growing, or plus end, of microtubules, and link microtubule ends to cellular structures. One best studied +TIPs is EB1, which forms comet-like structures tips growing microtubules. The molecular mechanisms by EB1 recognizes tracks largely unknown. However, one clue that can bind directly a end in absence other proteins. Here we use an vitro assay for dynamic growth with two-color total-internal-reflection-fluorescence imaging...
Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels. We describe here the presence of currents in melanoma cells that dependent on TMEM87a, which we have renamed Elkin1. Heterologous expression this protein PIEZO1-deficient cells, exhibit no baseline mechanosensitivity, sufficient to reconstitute currents. Melanoma lacking functional Elkin1 defective mechanoelectrical...
The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process not genetically regulated. However, mechanisms and chromatin modifications controlling timing are still unclear. We made use prominent structure defined heterochromatic landscape pericentric regions as an example late replicating constitutive heterochromatin. manipulated major markers these regions, namely histone acetylation, DNA methylation,...
Previous studies of mitosis show that capture single kinetochores by microtubules from both centrosomes (merotelic orientation) is a major cause aneuploidy. We have characterized hcp-6 , temperature-sensitive chromosome segregation mutant in C. elegans exhibits chromosomes attached to poles via sister kinetochore. demonstrate the primary defect this failure fully condense during prophase. Although centromere formation and resolution remain unaffected lack rigidity wild-type twist around long...
The precise coordination of the different steps DNA replication is critical for maintenance genome stability. We have probed mechanisms coupling various components machinery and their response to polymerase stalling by inhibition polymerases in living mammalian cells with aphidicolin. observed little change behaviour proteins involved initiation replication. In contrast, we detected a marked accumulation single stranded binding factor RPA34 at sites Finally, demonstrate that elongation step...
Co-polymers of tropomyosin and actin make up a major fraction the cytoskeleton. Tropomyosin isoforms determine function an filament by selectively enhancing or inhibiting association other binding proteins, altering stability regulating myosin activity in isoform-specific manner. Previous work has implicated specific roles for at least five different stress fibres, as depletion any these results loss fibres. Despite this, most models fibres continue to exclude tropomyosins. In this study, we...
Antimicrotubule vinca alkaloids are widely used in the clinic but their toxicity is often dose limiting. Strategies that enhance effectiveness at lower doses needed. We show combining with compounds target a specific population of actin filaments containing cancer-associated tropomyosin Tpm3.1 result synergy against broad range tumor cell types. discovered low concentrations vincristine alone induce supernumerary microtubule asters form transient multi-polar spindles early mitosis. Over time...
The actin cytoskeleton is a dynamic network of filaments that involved in virtually every cellular process. Most metazoa exist as co-polymer and tropomyosin (Tpm) the function an filament primarily defined by specific Tpm isoform associated with it. However, there little information on interdependence these co-polymers during assembly disassembly. We addressed this investigating recovery kinetics fluorescently tagged Tpm3.1 into bundles using FRAP analysis cell culture vivo rats...
Chromatin has been shown to undergo diffusional motion, which is affected during gene transcription by RNA polymerase activity. However, the relationship between chromatin mobility and other genomic processes remains unclear. Hence, we set out label DNA directly in a sequence unbiased manner followed labeled dynamics interphase human cells expressing GFP-tagged proliferating cell nuclear antigen (PCNA), cycle marker core component of replication machinery. We detected decreased S-phase...
Previous studies of the kinetochore in mammalian systems have demonstrated that this structure undergoes reorganizations after microtubule attachment or response to activation spindle checkpoint. Here, we show Caenorhabditis elegans displays analogous rearrangements at prometaphase, when microtubule/chromosome interactions are being established, and exposure checkpoint stimuli such as nocodazole anoxia. These characterized by a dissociation several proteins, including HCP-1/CeCENP-F,...
Centromeres form a chromosomal platform for the assembly of kinetochores, which are required orderly chromosome segregation. Assembly both centromeres and kinetochores proceeds by step-by-step mechanism that is regulated in time space. It has been suggested nuclear import centromeric proteins involved this process. We show knockdown nucleoporins NPP-10, NPP-13 NPP-20 Caenorhabditiselegans affects early steps centromere formation sister resolution, results severe defects embryo. These...
The HIV capsid is a multifunctional protein capsule that mediates the delivery of viral genetic material into nucleus target cell. Host cell proteins bind to number repeating binding sites on regulate steps in replication cycle. Here, we develop fluorescence fluctuation spectroscopy method using self-assembled particles as bait screen for fluorescence-labeled capsid-binding analytes ("prey" molecules) solution. assay capitalizes property multivalent interaction platform, facilitating high...
The HIV capsid is a multifunctional protein capsule for delivery of the viral genetic material into nucleus target cell. Host cell proteins bind to number repeating binding sites on regulate steps in replication cycle. Here we develop fluorescence fluctuation spectroscopy method using self-assembled particles as bait screen fluorescence-labelled capsid-binding analytes (‘prey’ molecules) solution. assay capitalizes property multivalent interaction platform, facilitating high sensitivity...
Chromatin has been shown to undergo diffusional motion, which is affected during gene transcription by RNA polymerase activity. However, the relationship between chromatin mobility and other genomic processes remains unclear. Hence, we set out label DNA directly in a sequence unbiased manner followed labeled dynamics interphase human cells expressing GFP-tagged proliferating cell nuclear antigen (PCNA), cycle marker core component of replication machinery. We detected decreased S-phase...
SUMMARY Chromatin has been shown to undergo diffusional motion, which is affected during gene transcription by RNA polymerase activity. However, the relationship between chromatin mobility and other genomic processes remains unclear. Hence, we set out label DNA directly in a sequence unbiased manner followed labeled dynamics interphase human cells expressing GFP-tagged PCNA, cell cycle marker core component of replication machinery. We detected decreased S-phase compared G1 G2 phases tumor...
<p>The measurement of spindle length and cell vertical length.</p>
<p>The combinations of anti-Tpm3.1 drugs and VCR show strong synergy in inducing apoptosis.</p>