- Malaria Research and Control
- Invertebrate Immune Response Mechanisms
- Mosquito-borne diseases and control
- Monoclonal and Polyclonal Antibodies Research
- Erythrocyte Function and Pathophysiology
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Magnesium in Health and Disease
- Ubiquitin and proteasome pathways
- Plant Micronutrient Interactions and Effects
- Advanced Biosensing Techniques and Applications
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Thyroid Cancer Diagnosis and Treatment
- Trace Elements in Health
- Blood groups and transfusion
- Neurofibromatosis and Schwannoma Cases
- Epigenetics and DNA Methylation
- Mass Spectrometry Techniques and Applications
- Galectins and Cancer Biology
- HIV Research and Treatment
- Trypanosoma species research and implications
- Meningioma and schwannoma management
Northumbria University
2020-2021
University of Plymouth
2013-2020
Peninsula College of Medicine and Dentistry
2018
Radboud University Nijmegen
2005-2016
Radboud University Medical Center
2005-2016
Radboud Institute for Molecular Life Sciences
2005-2016
University of Florence
2010
University of Southern Denmark
2002-2005
University Medical Center Groningen
1994-1996
University of Groningen
1990-1996
The human genome contains a number of methyl CpG binding proteins that translate DNA methylation into physiological response. To gain insight the function MBD2 and MBD3, we first applied protein tagging mass spectrometry. We show MBD3 assemble mutually exclusive distinct Mi-2/NuRD-like complexes, called MBD2/NuRD MBD3/NuRD. identified DOC-1, putative tumor suppressor, as novel core subunit well PRMT5 its cofactor MEP50 were specific interactors. stably specifically associates with methylates...
A universal feature of metazoan sexual development is the generation oocyte P granules that withhold certain mRNA species from translation to provide coding potential for proteins during early post-fertilization development. Stabilisation translationally quiescent pools in female Plasmodium gametocytes depends on RNA helicase DOZI, but molecular machinery involved silencing transcripts these protozoans unknown. Using affinity purification coupled with mass-spectrometric analysis we identify...
Despite over a century of study malaria parasites, parts the Plasmodium falciparum life cycle remain virtually unknown. One these is early gametocyte stage, round shaped cell morphologically similar to an asexual trophozoite in which major cellular transformations ensure subsequent development elongated gametocyte. We developed protocol obtain for first time highly purified preparations gametocytes using transgenic line expressing green fluorescent protein from onset gametocytogenesis....
Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization mosquitoes is essential for spreading disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report first transcriptome analysis male female Plasmodium falciparum coupled with a comprehensive proteome analysis. In there an enrichment proteins involved formation flagellated gametes; DNA replication, chromatin organization...
Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from -- early late oocysts containing midgut sporozoites, mature, infectious salivary gland sporozoites. Despite morphological similarity between their proteomes are markedly different, agreement with increase hepatocyte infectivity. The sporozoite contain large number stage specific proteins...
Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes, including cell cycle progression and cytoskeletal dynamics. A limited number of Cdk substrates have been identified with few demonstrated to be regulated by Cdk-dependent phosphorylation. We identify on protein expression arrays novel cyclin E–Cdk2 substrates, SIRT2, a member the Sirtuin family NAD+-dependent deacetylases that targets α-tubulin. define Ser-331 as site phosphorylated E–Cdk2, A–Cdk2, p35–Cdk5...
During storage of red cells (RBCs) for transfusion, RBCs undergo a number biochemical and morphologic changes. To be able to identify the mechanisms underlying these lesions, proteomic analysis membranes their vesicles was performed during various periods in blood bank conditions.RBCs were isolated from after periods. The proteins RBC separated by gel electrophoresis identified semiquantitative analysis.Our findings confirm previous data, such as storage-associated increase hemoglobin...
BACKGROUND: During storage of red cells (RBCs) for transfusion, RBCs undergo a number biochemical and morphologic changes. To be able to identify the mechanisms underlying these lesions, proteomic analysis membranes their vesicles was performed during various periods in blood bank conditions. STUDY DESIGN AND METHODS: were isolated from after periods. The proteins RBC separated by gel electrophoresis identified semiquantitative analysis. RESULTS: Our findings confirm previous data, such as...
The asexual blood stages of Plasmodium falciparum cause the most lethal form human malaria. During growth within an infected red cell, parasite multiplication and formation invasive merozoites is called schizogony. Here, we present a detailed analysis phosphoproteome P. schizonts revealing 2541 unique phosphorylation sites, including 871 novel sites. Prominent roles for cAMP-dependent protein kinase A- phosphatidylinositol-signaling were identified following by functional enrichment,...
Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested an infectious blood meal. Here, we determine transmission-reducing activity (TRA) of naturally acquired from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated antibody responses to Pfs48/45, Pfs230, and 43 novel gametocyte proteins assessed by protein microarray. In field-based assays likelihood rate...
TRPM6 and TRPM7 are bifunctional proteins expressing a TRP channel fused to an atypical α-kinase domain. While the gating properties of channels have been studied in detail, little is known about mechanisms regulating kinase activity. Recently, we found that associates with its substrate myosin II via kinase-dependent mechanism suggesting role for autophosphorylation recognition. Here, demonstrate cytosolic C-terminus undergoes massive (32±4 mol/mol), which strongly increases rate...
Orthology is a central tenet of comparative genomics and ortholog identification instrumental to protein function prediction. Major advances have been made determine orthology relations among set homologous proteins. However, they depend on the comparison individual sequences do not take into account divergent orthologs. We developed an iterative prediction method, Ortho-Profile, that uses reciprocal best hits at level sequence profiles infer orthology. It increases detection by 20% compared...
Dendritic cells (DCs) play a key role in orchestrating adaptive immune responses. In human blood, three distinct subsets exist: plasmacytoid DCs (pDCs) and BDCA3+ CD1c+ myeloid DCs. addition, DC-like CD16+ monocyte has been reported. Although RNA-expression profiles have previously compared, protein expression data may provide different picture. Here, we exploited label-free quantitative mass spectrometry to compare identify differences primary DC subset proteins. Moreover, integrated these...
Post-translational histone modifications abound and regulate multiple nuclear processes. Most are targeted to the amino-terminal domains of histones. Here we report identification characterization acetylation lysine 56 within core domain H3. In crystal structure nucleosome, contacts DNA. Phenotypic analysis suggests that is critical for function it modulates formamide resistance, ultraviolet radiation sensitivity, sensitivity hydroxyurea. We show acetylated form H3 (H3-K56) present during...
The human bowel contains a large and dynamic bacterial population that is not only essential for intestinal health, but also critical the development of diseases such as cancer. In this respect, Gram-positive bacterium Streptococcus bovis has been associated with colon cancer many years. To investigate clinical importance association, an immunocapture mass spectrometry assay was developed can generate infection-related protein profiles. composition these profiles governed by capture specific...
MINT‐6700314: GNA1 (uniprotkb:Q96EK6) and bind (MI:0407) by X-ray crystallography (MI:0114)