Sergi Castellano
A5021550271- Selenium in Biological Systems
- Trace Elements in Health
- Forensic and Genetic Research
- Genomics and Phylogenetic Studies
- Single-cell and spatial transcriptomics
- Mercury impact and mitigation studies
- Pluripotent Stem Cells Research
- CAR-T cell therapy research
- Viral gastroenteritis research and epidemiology
- Pituitary Gland Disorders and Treatments
- Genetic diversity and population structure
- Race, Genetics, and Society
- Primate Behavior and Ecology
- Pleistocene-Era Hominins and Archaeology
- Animal Diversity and Health Studies
- Chromosomal and Genetic Variations
- Animal Virus Infections Studies
- Corneal Surgery and Treatments
- Nanowire Synthesis and Applications
- CRISPR and Genetic Engineering
- Phytase and its Applications
- Inflammatory Myopathies and Dermatomyositis
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
Great Ormond Street Hospital
2018-2024
University College London
2018-2024
Genomics England
2018-2024
Genomics (United Kingdom)
2018-2023
Institut thématique Génétique, génomique et bioinformatique
2022
Max Planck Institute for Evolutionary Anthropology
2009-2019
Max Planck Society
2009-2016
Cornell University
2009
University of Hawaiʻi at Mānoa
2008
Janelia Research Campus
2007
In the genetic code, UGA serves as a stop signal and selenocysteine codon, but no computational methods for identifying its coding function are available. Consequently, most selenoprotein genes misannotated. We identified in sequenced mammalian genomes by that rely on identification of insertion RNA structures, potential codons, presence cysteine-containing homologs. The human selenoproteome consists 25 selenoproteins.
Our closest living relatives, chimpanzees and bonobos, have a complex demographic history. We analyzed the high-coverage whole genomes of 75 wild-born bonobos from 10 countries in Africa. found that chimpanzee population substructure makes genetic information good predictor geographic origin at country regional scales. Multiple lines evidence suggest gene flow occurred into ancestors central eastern between 200,000 550,000 years ago, probably with subsequent spread Nigeria-Cameroon...
Significance We use a hybridization approach to enrich the DNA from protein-coding fraction of genomes two Neandertal individuals Spain and Croatia. By analyzing these exomes together with genome sequence Siberia we show that genetic diversity Neandertals was lower than present-day humans pattern coding variation suggests populations were small isolated one another. also genes involved in skeletal morphology have changed more expected on evolutionary lineage whereas pigmentation behavior...
The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, GPX6 (glutathione peroxidases), DIO1, DIO2, DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), SEPHS2 (selenophosphate synthetase...
Abstract Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis children have been reported worldwide, including 278 the UK 1 . Here we report an investigation 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination genomic, transcriptomic, proteomic immunohistochemical methods. We detected high levels adeno-associated virus 2 (AAV2) DNA liver, blood, plasma or stool from 27 28 cases....
Sequencing the genomes of extinct hominids has reshaped our understanding modern human origins. Here, we analyze ∼120 kb exome-captured Y-chromosome DNA from a Neandertal individual El Sidrón, Spain. We investigate its divergence orthologous chimpanzee and sequences find strong support for model that places lineage as an outgroup to Y chromosomes-including A00, highly divergent basal haplogroup. estimate time most recent common ancestor (TMRCA) chromosomes is ∼588 thousand years ago (kya)...
Selenoproteins are a diverse group of proteins that contain selenocysteine (Sec), the 21st amino acid. In genetic code, UGA serves as termination signal and Sec codon. This dual role has precluded automatic annotation selenoproteins. Recent advances in computational identification selenoprotein genes have provided first glimpse size, functions, phylogenetic diversity eukaryotic selenoproteomes. Here, we describe family named SelJ. contrast to known selenoproteins, SelJ appears be restricted...
We sequenced genomes from a ∼7,000 year old early farmer Stuttgart in Germany, an ∼8,000 hunter-gatherer Luxembourg, and seven hunter-gatherers southern Sweden. analyzed these data together with other ancient 2,345 contemporary humans to show that the great majority of present-day Europeans derive at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry all but not Near Easterners; Ancient North Eurasians (ANE), were most closely...
To define the host mechanisms contributing to pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM).
The use of induced pluripotent stem cells (iPSC) as models for development and human disease has enabled the study otherwise inaccessible tissues. A remaining challenge in developing reliable is our limited understanding factors driving irregular differentiation iPSCs, particularly impact acquired somatic mutations. We leveraged data from a pooled dopaminergic neuron experiment 238 iPSC lines profiled with single-cell RNA whole-exome sequencing to how mutations affect outcomes. found that...
Selenoproteins are a diverse group of proteins usually misidentified and misannotated in sequence databases. The presence an in-frame UGA (stop) codon the coding selenoprotein genes precludes their identification correct annotation. codons recoded to cotranslationally incorporate selenocysteine, rare selenium-containing amino acid. development ad hoc experimental and, more recently, computational approaches have allowed efficient characterization selenoproteomes growing number species....
SelenoDB (http://www.selenodb.org) aims to provide high-quality annotations of selenoprotein genes, proteins and SECIS elements. Selenoproteins are that contain the amino acid selenocysteine (Sec) first release database included for eight species. Since 1.0 many new animal genomes have been sequenced. The selenoproteins in usually errors major databases. For this reason, we now fully annotated genes 58 genomes. We manually curated human selenoproteins, whereas use an automatic annotation...
As humans migrated around the world, they came to inhabit environments that differ widely in soil levels of certain micronutrients, including selenium (Se). Coupled with cultural variation dietary practices, these migrations have led a wide range Se intake populations world. Both excess and deficiency diet can adverse health consequences humans, severe resulting diseases bone heart. is required by mainly due its function selenoproteins, which contain amino acid selenocysteine as one their...
Summary Since the first reports of hepatitis unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 UK, with majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation 28 136 control subjects. In five who underwent liver transplantation, detected high levels adeno-associated virus 2 (AAV2) explanted livers. AAV2 was also at blood from 10/11 non-transplanted cases. Low...
Selenocysteine (Sec), the 21st amino acid, is incorporated into proteins through recoding of a termination codon, an inefficient translational process mediated by complex molecular machinery. Sec rare acid in extant proteins, chemically similar to cysteine (Cys), found homologous position Cys nonselenoprotein families. Selenoproteins account for dependence vertebrates on environmental selenium (Se) and have important role several Se-deficiency diseases. are poorly characterized enzymes...
Chimpanzees, humans' closest relatives, are in danger of extinction. Aside from direct human impacts such as hunting and habitat destruction, a key threat is transmissible disease. As humans continue to encroach upon their habitats, which shrink size grow density, the risk inter-population cross-species viral transmission increases, point dramatically made reverse with global HIV/AIDS pandemic. Inhabiting central Africa, four subspecies chimpanzees differ demographic history geographical...
Abstract We recently described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that showed enhanced expansion, cytotoxicity, and antitumor efficacy compared with the high-affinity (FMC63-based) CAR used in tisagenlecleucel, preclinical models. Furthermore, demonstrated an excellent toxicity profile, vivo long-term persistence phase 1 clinical study. To understand molecular mechanisms behind these properties of T cells, we performed systematic vitro characterization...
Abstract The two types of craniopharyngioma, adamantinomatous (ACP) and papillary (PCP), are clinically relevant tumours in children adults. Although the biology primary craniopharyngioma is starting to be unravelled, little known about recurrence. To fill this gap knowledge, we have analysed through methylation array, RNA sequencing pERK1/2 immunohistochemistry a cohort paired recurrent samples (32 from 14 cases ACP 4 PCP). We show presence copy number alterations clonal evolution across...