- Microtubule and mitosis dynamics
- Photosynthetic Processes and Mechanisms
- Genetic and Kidney Cyst Diseases
- Nuclear Structure and Function
- Protist diversity and phylogeny
- RNA Research and Splicing
- CAR-T cell therapy research
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and biosynthesis
- Cancer Immunotherapy and Biomarkers
- Hepatitis B Virus Studies
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Axon Guidance and Neuronal Signaling
- Monoclonal and Polyclonal Antibodies Research
- Diet, Metabolism, and Disease
- Protein Kinase Regulation and GTPase Signaling
- Cancer Cells and Metastasis
- 14-3-3 protein interactions
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
AstraZeneca (United Kingdom)
2018-2022
MRC Laboratory for Molecular Cell Biology
2017-2018
MRC Laboratory of Molecular Biology
2013-2018
Medical Research Council
2014
The Gurdon Institute
2007-2010
Centrosomes comprise a pair of centrioles surrounded by pericentriolar material (PCM). The PCM expands dramatically as cells enter mitosis, but it is unclear how this occurs. In study, we show that the centriole protein Asl initiates recruitment DSpd-2 and Cnn to mother centrioles; both proteins then assemble into co-dependent scaffold-like structures spread outwards from recruit most, if not all, other components. absence either or Cnn, mitotic assembly diminished; in proteins, appears be...
The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein its accessory complex dynactin with dynamic plus ends. Here, we elucidate vitro the roles dynactin, end-binding protein-1 (EB1) Lissencephaly-1 (LIS1) interaction end tracking minus end-directed human complexes these sites. LIS1 promotes dynactin-dependent on both growing shrinking also increases frequency velocity...
Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition transported ribonucleoprotein particles (RNPs) and regulation their movement are poorly understood. We have reconstituted microtubule minus end-directed mRNAs using purified components. A Bicaudal-D (BicD) adaptor RNA-binding Egalitarian (Egl) sufficient long-distance by dynein motor its accessory complex dynactin, thus defining minimal transport-competent RNP. Unexpectedly,...
Programmed cell death ligand-1 (PD-L1) expression levels in patient tumor samples have proven clinical utility across various cancer types. Several independently developed PD-L1 immunohistochemical (IHC) predictive assays are commercially available. Published studies using the VENTANA (SP263) Assay, (SP142) Dako IHC 22C3 pharmDx assay, 28-8 and laboratory-developed tests utilizing E1L3N antibody (Cell Signaling Technology), demonstrated differing of staining between assays, resulting...
In C. elegans, genome-wide screens have identified just five essential centriole-duplication factors: SPD-2, ZYG-1, SAS-5, SAS-6, and SAS-4 [1-8]. These proteins are widely believed to comprise a conserved core duplication module [3, 9-14]. worm embryos, SPD-2 is the most upstream component of this module, it also for pericentriolar material (PCM) recruitment centrioles [1, 4, 15, 16]. Here, we show that Drosophila Spd-2 (DSpd-2) both PCM has role in recruiting centrioles. DSpd-2 appears...
Microtubule-based transport mediates the sorting and dispersal of many cellular components pathogens. However, mechanisms by which motor complexes are recruited to regulated on different cargos remain poorly understood. Here we describe a large-scale biochemical screen for novel factors associated with RNA localization signals mediating minus end–directed mRNA during Drosophila development. We identified protein Lissencephaly-1 (Lis1) found that minus-end travel distances localizing...
Abstract Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has genetic component but, despite the common variants already identified, there still missing heritability component. Using candidate gene approach, we identify locus (rs71519934) at Pleckstrin and Sec7 domain-containing 3 ( PSD3 ) resulting in leucine to threonine substitution position 186 of protein (L186T) that reduces susceptibility entire spectrum individuals risk. downregulation by...
Abstract In nonalcoholic fatty liver disease (NAFLD) the patatin‐like phospholipase domain‐containing 3 ( PNPLA3 ) rs738409 variant is a contributor. mice, Pnpla3 148M accumulates on lipid droplets and probably leads to sequestration of lipase cofactor leading impaired mobilization triglycerides. To advance our understanding localization abundance protein in humans, we used biopsies from patients with NAFLD investigate link genotype. We experimentally qualified an antibody against human...
Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition transported ribonucleoprotein particles (RNPs) and regulation their movement are poorly understood. We have reconstituted microtubule minus end-directed mRNAs using purified components. A Bicaudal-D (BicD) adaptor RNA-binding Egalitarian (Egl) sufficient long-distance by dynein motor its accessory complex dynactin, thus defining minimal transport-competent RNP. Unexpectedly,...